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- Ahmed, S, et al.
(författare)
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Host-Directed Therapy as a Novel Treatment Strategy to Overcome Tuberculosis: Targeting Immune Modulation
- 2020
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Ingår i: Antibiotics (Basel, Switzerland). - : MDPI AG. - 2079-6382. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Tuberculosis (TB) is one of the leading causes of mortality and morbidity, particularly in developing countries, presenting a major threat to the public health. The currently recommended long term treatment regimen with multiple antibiotics is associated with poor patient compliance, which in turn, may contribute to the emergence of multi-drug resistant TB (MDR-TB). The low global treatment efficacy of MDR-TB has highlighted the necessity to develop novel treatment options. Host-directed therapy (HDT) together with current standard anti-TB treatments, has gained considerable interest, as HDT targets novel host immune mechanisms. These immune mechanisms would otherwise bypass the antibiotic bactericidal targets to kill Mycobacterium tuberculosis (Mtb), which may be mutated to cause antibiotic resistance. Additionally, host-directed therapies against TB have been shown to be associated with reduced lung pathology and improved disease outcome, most likely via the modulation of host immune responses. This review will provide an update of host-directed therapies and their mechanism(s) of action against Mycobacterium tuberculosis.
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- Bergsson, G, et al.
(författare)
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Antimicrobial components of vernix caseosa
- 2004
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Ingår i: PEDIATRIC RESEARCH. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 56:3, s. 469-469
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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- Cederlund, A, et al.
(författare)
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Label-free quantitative mass spectrometry reveals novel pathways involved in LL-37 expression
- 2014
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Ingår i: Journal of innate immunity. - : S. Karger AG. - 1662-8128 .- 1662-811X. ; 6:3, s. 365-376
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial peptides are important for a healthy host-microbe homeostasis. In infections characterized by low levels of the human cathelicidin, LL-37, induction of its expression increases clearance of pathogens. Our aim was to discover signaling pathways and compounds capable of affecting the expression of LL-37. We recently observed a synergistic induction of LL-37 expression by stimulating the colonic epithelial cell-line HT-29 with lactose and phenylbutyrate (PBA). Here, we studied regulatory circuits mediating this synergism in HT-29 cells stimulated with lactose (60 g/l) and PBA (2 m<smlcap>M</smlcap>) for 24 h by using mass spectrometry and pathway analyses. Selected pathways were evaluated for their involvement in LL-37 regulation in a <i>CAMP</i> gene-luciferase reporter system. Three pathways were examined in detail: thyroid hormone receptor and retinoid X receptor (TR/RXR) activation, eicosanoid signaling and steroid biosynthesis. Induced expression of LL-37 was observed upon stimulation with triiodothyronine (T3, 2.5 n<smlcap>M</smlcap>-1 µ<smlcap>M</smlcap> for 3-30 h) and thyroxine (T4, 2.5-10 n<smlcap>M</smlcap> for 24 h). Furthermore, the synergism of lactose and PBA was reduced in cells coincubated with inhibitors of phospholipase A2, cyclooxygenase 2 or HMG-CoA reductase. Based on these results, we conclude that proteomics and pathway analyses are valuable tools for dissecting the regulatory networks involved in LL-37 expression.
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- Dubiel, M, et al.
(författare)
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Computer analysis of three-dimensional power angiography images of foetal cerebral, lung and placental circulation in normal and high-risk pregnancy
- 2005
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Ingår i: Ultrasound in Medicine and Biology. - : Elsevier BV. - 0301-5629. ; 31:3, s. 321-327
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Tidskriftsartikel (refereegranskat)abstract
- Three-dimensional (3-D) ultrasound (US) has greatly improved evaluation of organ circulation. The aim of this study was to explore the possible use of this new technique in normal and high-risk pregnancies. Fetal brain, lung and placenta 3-D power Doppler signal intensity were recorded in 115 normal singleton pregnancies (24 to 42 weeks gestation) and in 67 high-risk pregnancies. Mean image pixel signal intensity was calculated for each organ and a brain-lung ratio. In normal pregnancy, placental and lung signal intensity increased until 33, with a rapid decrease after 38, weeks of gestation. Fetal cerebral signal intensity increased with gestational age. Placental and fetal lung signal intensity was significantly lower in high-risk pregnancies than in the control group, with increased fetal brain and brain-lung ratios. The present results suggest a reduction of placental perfusion after 38 weeks of gestation in normal pregnancy, with redistribution of fetal circulation. Lung signal intensity increased abruptly at 32 weeks of gestation, which might reflect lung maturity. The new method showed signs of centralization of fetal circulation at the end of gestation. The results might suggest a possible clinical use for fetal surveillance in high-risk pregnancies.
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| 28. |
- Dubiel, M, et al.
(författare)
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Evaluation of fetal circulation redistribution in pregnancies with absent or reversed diastolic flow in the umbilical artery
- 2003
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Ingår i: Early Human Development. - 1872-6232. ; 71:2, s. 149-156
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To record blood flow velocimetry in the superior mesenteric, hepatic and middle cerebral arteries for detection of circulation redistribution and prediction of perinatal outcome in fetuses with absent or reversed diastolic flow in the umbilical artery. Study design: The fetal superior mesenteric, hepatic and middle cerebral artery blood velocimetry was recorded in 33 pregnancies complicated by pregnancy-induced hypertension and/or intra-uterine growth retardation between 27 and 41 weeks of gestation. Uterine artery and umbilical vein velocimetries were also recorded. Results: An abnormal mesenteric artery pulsatility, index (PI) was found in four cases; two newborns died due to prematurity, growth retardation and necrotizing enterocolitis. An abnormal fetal hepatic artery PI was found in 17 cases. The brain-sparing effect in the middle cerebral artery was found in 16 cases; three newborns died after delivery. Signs of redistribution in mesenteric, hepatic and middle cerebral artery velocimetry were not related to most of the perinatal outcome variables. Umbilical vein velocimetry correlated with low arterial and venous pH. All perinatal mortalities had umbilical venous pulsations. Conclusions: Signs of visceral circulation redistribution could not predict adverse outcome. Umbilical venous pulsations were, however, seen in nearly all fetuses; this was the only variable suggesting adverse outcome in the present study of severely compromised fetuses. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.
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| 29. |
- Dubiel, M, et al.
(författare)
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Fetal and maternal Doppler velocimetry and cytokines in high-risk pregnancy
- 2005
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Ingår i: Journal of Perinatal Medicine. - 1619-3997. ; 33:1, s. 17-21
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Fetal hypoxia and preterm delivery are reported to be strongly associated with brain damage and neurodevelopmental delay. Doppler signs of fetal brain sparing have been described during chronic hypoxia, but whether they are related to brain damage is unknown. The aim of this study was to evaluate if markers of tissue injury, i.e., tumor necrosis factor-alpha. (TNF-alpha) and interleukin-6 (IL-6) are related to signs of increased perinatal vascular impedance and/or fetal brain sparing in high-risk pregnancies. Study design: TNF-alpha and IL-6 levels were evaluated in maternal blood serum of 67 high-risk pregnancies. Serum samples were taken at the time of umbilical, middle cerebral artery and uterine artery Doppler velocimetry examination. The values for TNF-alpha and IL-6 were correlated with reference median values obtained with gestational age in the form of a Z-score. Results: TNF-alpha levels showed values within the normal range in only four cases. IL-6 values were found normal in 14 cases. The Z-score for mean middle cerebral artery pulsatility index (PI) showed a significant correlation to TNF-alpha and IL-6 levels, P < 0.0001 and P < 0.003, respectively. This might suggest a strong correlation between signs of fetal brain sparing and increased maternal serum TNF-alpha and IL-6 levels. Abnormal uterine artery PI and the presence of a "notch" were also highly significantly related to TNF-alpha and IL-6 levels, which were nearly two-fold higher compared to normal uterine artery blood flow and the absence of a "notch". Abnormal cerebro/placental ratios showed significant correlations to TNF-alpha and IL-6 levels. Conclusion: The present results suggest a strong correlation between levels of TNF-a and IL-6 not only for signs of fetal brain sparing, but also for uteroplacental blood flow. This finding supports the role of tissue injury in cases of fetal brain sparing, but whether this is a reflection of brain damage or secondary to placental pathology needs further evaluation.
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- GUDMUNDSSON, GH, et al.
(författare)
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Structure of the gene for porcine peptide antibiotic PR-39, a cathelin gene family member: comparative mapping of the locus for the human peptide antibiotic FALL-39
- 1995
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 92:15, s. 7085-7089
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Tidskriftsartikel (refereegranskat)abstract
- PR-39 is a porcine 39-aa peptide antibiotic composed of 49% proline and 24% arginine, with an activity against Gram-negative bacteria comparable to that of tetracycline. In Escherichia coli, it inhibits DNA and protein synthesis. PR-39 was originally isolated from pig small intestine, but subsequent cDNA cloning showed that the gene is expressed in the bone marrow. The open reading frame of the clone showed that PR-39 is made as 173-aa precursor whose proregion belongs to the cathelin family. The PR39 gene, which is rather compact and spans only 1784 bp has now been sequenced. The coding information is split into four exons. The first exon contains the signal sequence of 29 residues and the first 37 residues of the cathelin propart. Exons 2 and 3 contain only cathelin information, while exon 4 codes for the four C-terminal cathelin residues and the mature PR-39 peptide extended by three residues. The sequenced upstream region (1183 bp) contains four potential recognition sites for NF-IL6 and three for APRF, transcription factors known to regulate genes for both cytokines and acute phase response factors. Genomic hybridizations revealed a fairly high level of restriction fragment length polymorphism and indicated that there are at least two copies of the PR39 gene in the pig genome. PR39 was mapped to pig chromosome 13 by linkage and in situ hybridization mapping. The gene for the human peptide antibiotic FALL-39 (also a member of the cathelin family) was mapped to human chromosome 3, which is homologous to pig chromosome 13.
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| 44. |
- Jorgensen, GH, et al.
(författare)
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Familial aggregation of IgAD and autoimmunity
- 2009
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Ingår i: Clinical immunology (Orlando, Fla.). - : Elsevier BV. - 1521-7035 .- 1521-6616. ; 131:2, s. 233-239
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Tidskriftsartikel (refereegranskat)
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