| 1. |
- Hederos, Carl-Axel, et al.
(författare)
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Comparison of clinically diagnosed asthma with parental assessment of children's asthma in a questionnaire
- 2007
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Ingår i: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 18:2, s. 135-141
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological evaluations of the prevalence of asthma are usually based on written questionnaires (WQs) in combination with validation by clinical investigation. In the present investigation, we compared parental assessment of asthma among their preschool children in response to a WQ with the corresponding medical records in the same region. An International Study of Asthma and Allergies in Childhood (ISAAC)-based WQ was answered by 75% of the parents of 6295 children aged 1–6 yr. Clinically diagnosed asthma, recorded in connection with admissions to the hospital or a visit to any of the outpatient clinics in the same region, were analysed in parallel. Finally, a complementary WQ was sent to the parents of children identified as asthmatic by either or both of this approaches. In response to the WQ 5.9% were claimed to suffer from asthma diagnosed by a doctor. According to the medical records, the prevalence of clinically diagnosed asthma was 4.9%. The estimated prevalence among children requiring treatment for their asthma was 4.4%. The sensitivity of the WQ was 77%, the specificity 97.5%. In the 1–2 yr age group the sensitivity was only 22%. This WQ was able to identify 54% of the children with a medical record of asthma. Forty percent of the children claimed by their parents to be asthmatic had no medical record of asthma. An ISAAC-based parentally completed WQ provided an acceptable estimation of the prevalence of asthma in children 2–6 yr of age, although only half of the individual patients identified in this manner are the same as those identified clinically.
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| 2. |
- Jakobsson, Johan, et al.
(författare)
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Potential physiological and cellular mechanisms of exercise that decrease the risk of severe complications and mortality following sars-cov-2 infection
- 2021
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Ingår i: Sports. - : MDPI. - 2075-4663. ; 9:9
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Forskningsöversikt (refereegranskat)abstract
- The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has unmasked mankind's vulnerability to biological threats. Although higher age is a major risk factor for disease severity in COVID-19, several predisposing risk factors for mortality are related to low cardiorespiratory and metabolic fitness, including obesity, cardiovascular disease, diabetes, and hypertension. Reaching physical activity (PA) guideline goals contribute to protect against numerous immune and inflammatory disorders, in addition to multi-morbidities and mortality. Elevated levels of cardiorespiratory fitness, being non-obese, and regular PA improves immunological function, mitigating sustained low-grade systemic inflammation and age-related deterioration of the immune system, or immunosenescence. Regular PA and being non-obese also improve the antibody response to vaccination. In this review, we highlight potential physiological, cellular, and molecular mechanisms that are affected by regular PA, increase the host antiviral defense, and may determine the course and outcome of COVID-19. Not only are the immune system and regular PA in relation to COVID-19 discussed, but also the cardiovascular, respiratory, renal, and hormonal systems, as well as skeletal muscle, epigenetics, and mitochondrial function.
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| 3. |
- Borde, Annika, 1979, et al.
(författare)
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Preparation and evaluation of a freeze-dried oral killed cholera vaccine formulation
- 2011
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 79:3, s. 508-518
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Tidskriftsartikel (refereegranskat)abstract
- Different oral liquid cholera vaccines have proved to be safe and effective, but their formulations present problems for use in low-income countries, since large package volumes have to be transported and cold chain maintenance is required. A solid state formulation would here be more advantageous, and consequently, the possibility to develop a dry cholera vaccine formulation by freeze-drying was investigated. The ability of sucrose, trehalose and mannitol to provide process stabilization during freeze-drying was tested on a formalin-killed whole-cell Vibrio cholerae model vaccine. A matrix of sucrose or trehalose prevented bacterial aggregation, preserved cell morphology and maintained practically completely the protective lipopolysaccharide (LPS) antigen on the cell surface and its reactivity with specific antibody in vitro. After reconstitution, this formulation also retained the capacity to elicit a strong serum and gut mucosal anti-LPS antibody response in orally immunized mice, as compared to the corresponding liquid vaccine formulation. The full preservation of the in vivo immunogenicity was also maintained when the internationally widely licensed oral cholera vaccine Dukoral (TM), which comprises a cocktail of inactivated V. cholerae together with cholera toxin B-subunit (CTB), was freeze-dried using sucrose for stabilization. Thus, we present a process generating a dry oral inactivated whole-cell cholera vaccine formulation with attractive features for public health use in cholera-afflicted settings.
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| 4. |
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| 5. |
- Mahlapuu, Margit, 1972, et al.
(författare)
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Antimicrobial Peptides : An Emerging Category of Therapeutic Agents
- 2016
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Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media SA. - 2235-2988. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial peptides (AMPs), also known as host defense peptides, are short and generally positively charged peptides found in a wide variety of life forms from microorganisms to humans. Most AMPs have the ability to kill microbial pathogens directly, whereas others act indirectly by modulating the host defense systems. Against a background of rapidly increasing resistance development to conventional antibiotics all over the world, efforts to bring AMPs into clinical use are accelerating. Several AMPs are currently being evaluated in clinical trials as novel anti-infectives, but also as new pharmacological agents to modulate the immune response, promote wound healing, and prevent post-surgical adhesions. In this review, we provide an overview of the biological role, classification, and mode of action of AMPs, discuss the opportunities and challenges to develop these peptides for clinical applications, and review the innovative formulation strategies for application of AMPs
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| 6. |
- Ågren, Joakim, et al.
(författare)
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In silico and in vitro evaluation of PCR-based assays for the detection of Bacillus anthracis chromosomal signature sequences
- 2013
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Ingår i: Virulence. - : Taylor and Francis Inc.. - 2150-5594 .- 2150-5608. ; 4:8
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Tidskriftsartikel (refereegranskat)abstract
- Bacillus anthracis, the causative agent of anthrax, is a zoonotic pathogen that is relatively common throughout the world and may cause life threatening diseases in animals and humans. There are many PCR-based assays in use for the detection of B. anthracis. While most of the developed assays rely on unique markers present on virulence plasmids pXO1 and pXO2, relatively few assays incorporate chromosomal DNA markers due to the close relatedness of B. anthracis to the B. cereus group strains. For the detection of chromosomal DNA, different genes have been used, such as BA813, rpoB, gyrA, plcR, S-layer, and prophage-lambda. Following a review of the literature, an in silico analysis of all signature sequences reported for identification of B. anthracis was conducted. Published primer and probe sequences were compared for specificity against 134 available Bacillus spp. genomes. Although many of the chromosomal targets evaluated are claimed to be specific to B. anthracis, cross-reactions with closely related B. cereus and B. thuringiensis strains were often observed. Of the 35 investigated PCR assays, only 4 were 100% specific for the B. anthracis chromosome. An interlaboratory ring trial among five European laboratories was then performed to evaluate six assays, including the WHO recommended procedures, using a collection of 90 Bacillus strains. Three assays performed adequately, yielding no false positive or negative results. All three assays target chromosomal markers located within the lambdaBa03 prophage region (PL3, BA5345, and BA5357). Detection limit was further assessed for one of these highly specific assays. © 2013 Landes Bioscience.
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| 7. |
- Lebens, Michael, 1956, et al.
(författare)
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Construction and preclinical evaluation of mmCT, a novel mutant cholera toxin adjuvant that can be efficiently produced in genetically manipulated Vibrio cholerae
- 2016
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Ingår i: Vaccine. - : Elsevier Ltd. - 0264-410X .- 1873-2518. ; 34:18, s. 2121-2128
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Tidskriftsartikel (refereegranskat)abstract
- There is an urgent need for new adjuvants that are effective with mucosally administered vaccines. Cholera toxin (CT) is the most powerful known mucosal adjuvant but is much too toxic for human use. In an effort to develop a useful mucosal adjuvant we have generated a novel non-toxic mutant CT molecule that retains much of the adjuvant activity of native CT. This was achieved by making the enzymatically active A subunit (CTA) recalcitrant to the site-specific proteolytic cleavage ("nicking") required for toxicity, which was found to require mutations not only in the two residues rendering the molecule resistant to trypsin but also in neighboring sites protecting against cleavage by Vibrio cholerae proteases. This multiple-mutated CT (mmCT) adjuvant protein could be efficiently produced in and purified from the extracellular medium of CT-deleted V. cholerae. The mmCT completely lacked detectable enterotoxicity in an infant mouse model and had >1000-fold reduced cAMP inducing activity compared to native CT in a sensitive mammalian target cell system. It nonetheless proved to have potent adjuvant activity on mucosal and systemic antibody as well as cellular immune responses to mucosally co-administered antigens including oral cholera and intranasal influenza vaccines. We conclude that mmCT is an attractive novel non-toxic mucosal adjuvant for enhancing immune responses to co-administered mucosal vaccines
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| 8. |
- George-Chandy, Annie, 1969, et al.
(författare)
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Th17 development and autoimmune arthritis in the absence of reactive oxygen species
- 2008
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Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 38:4, s. 1118-1126
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Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells (DC) express a functional NADPH oxidase and produce reactive oxygen species (ROS) upon interaction with microbes and T cells. Exposure to ROS leads to DC activation and maturation, as evidenced by phenotypic and functional changes. We have evaluated how endogenous ROS production affects the cytokine secretion pattern and T cell-activating capacity of bone marrow-derived murine DC. DC treated with ROS scavengers, as well as DC from mice that lack a functional NADPH oxidase (and thereby inherently deficient in ROS production) produced significantly increased levels of IL-1β, IL-6, TNF-α and TGF-β in response to microbial activation. DC deficient in ROS production induced high levels of IFN-γ and IL-17 in responding T cells after Ag-specific or superantigen-induced activation. Finally, we show that ROS deficiency affected the induction of a T cell-dependent inflammatory condition, collagen-induced arthritis (CIA). C57BL/6 mice that lack a functional NADPH oxidase developed a severe and erosive CD4-dependent CIA, whereas the majority of the congenic wild-type animals remained healthy. These data suggest that ROS act as immunomodulators in DC-driven T cell activation and perhaps also in T cell-dependent immunopathology.
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| 9. |
- Nygren, Erik, et al.
(författare)
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Establishment of an adult mouse model for direct evaluation of the efficacy of vaccines against Vibrio cholerae
- 2009
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 77:8, s. 3475-3484
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Tidskriftsartikel (refereegranskat)abstract
- We describe here a new animal model that offers the prospect of using conventional adult mice for direct evaluation of the protective potential of new cholera vaccines. Pretreatment of adult mice with oral streptomycin allowed intestinal colonization by streptomycin-resistant Vibrio cholerae strains of either the O1 or the O139 serogroup. Bacteria were recovered in greatest numbers from the cecum and large intestine, but recoveries from all regions of the gut correlated significantly with bacterial excretion in fresh fecal pellets, which thus provides a convenient indicator of the extent and duration of gut colonization. Mice immunized mucosally or systemically with viable or inactivated V. cholerae were shown to be comparatively refractory to colonization after challenge with the immunizing strain. Several variables were examined to optimize the model, the most significant being the size of the challenge inoculum; surprisingly, a smaller challenge dose resulted in more consistent and sustained colonization. Studies with mutant strains unable to produce cholera toxin or toxin-coregulated pili revealed that neither factor contributed significantly to colonization potential. Protection against V. cholerae challenge was shown to be serogroup restricted, and significant inverse correlations were detected between serum and intestinal anti-lipopolysaccharide antibody responses and the levels of excretion of challenge organisms.
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| 10. |
- Nygren, Erik, 1976, et al.
(författare)
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Murine antibody responses following systemic or mucosal immunization with viable or inactivated Vibrio cholerae.
- 2008
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 26:52, s. 6784-90
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Tidskriftsartikel (refereegranskat)abstract
- Protocols are described for the induction of strong, consistent serum and mucosal antibody responses to Vibrio cholerae O1 or O139 lipopolysaccharide (LPS) following intranasal or oral immunization of adult mice with viable or formalin-killed bacteria. A simplified two-dose schedule for intranasal immunization has been identified, whereby viable bacteria elicit strong serum responses and, most importantly, also induce significant, sustained intestinal IgA responses. Using higher doses of bacteria it was also possible to generate consistently high intestinal and serum anti-LPS responses by the oral route. The efficacy of these immunization schedules was not dependent on co-administration of adjuvant. Gut responses were estimated using two sampling techniques involving the collection of fresh faecal pellets or the preparation of intestinal tissue extracts. The significant correlation between these estimates validates the more convenient approach of measuring intestinal responses using faecal pellet extracts, which allows repeated sampling from the same animals. V. cholerae O1 and O139 were similarly immunogenic by either mucosal route. More intensive immunization schedules for administration of formalin-killed bacteria have also been defined. Using these regimes it was possible to generate serum and gut antibody responses comparable to those elicited by viable V. cholerae. The established immunization protocols will allow evaluation of the systemic and mucosal immunogenicity of new vaccine formulations.
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