| 1. |
- Abdalla, Hana, et al.
(författare)
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Effects of CNI-1493 on human granulocyte functions
- 2006
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Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985 .- 1878-3279. ; 211:3, s. 191-197
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Tidskriftsartikel (refereegranskat)abstract
- During acute bacterial infections such as sepsis and meningitis, activation of inflammatory mediators such as nitric oxide (NO) plays a crucial role in both pathogenesis and host defense. We have previously reported that CNI-1493, a macrophage deactivator, reduced mortality in infant rats infected with Haemophilus influenzae type b (Hib) with associated decrease in the number of granulocytes in the infected tissue. The aim of the present study was to investigate how CNI-1493 affects granulocytes and macrophages in vitro. Murine macrophages (RAW 264.7) pre-incubated with CNI-1493 prior to activation with lipopolysaccharide (LPS)/interferon gamma (IFNγ) had decreased NO production measured as NO2−/NO3− levels and reduction in inducible NO-synthase (iNOS) expression. Reactive oxygen species (ROS) production was increased in formylmethionyl-leucyl-phenylalanine (FMLP)-stimulated granulocytes following CNI-1493 treatment, whereas F-actin content, motility and chemotaxis were decreased under the same conditions. The effects of CNI-1493 on both NO production in LPS/IFNγ-activated macrophages and ROS production, F-actin content, motility and chemotaxis in granulocytes, may contribute to the reduced inflammatory response and increased survival in Hib-infected animals treated with CNI-1493.
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| 2. |
- Abdalla, Hana, et al.
(författare)
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Expression of inducible nitric oxide synthases and nitrotyrosine during the course of Haemophilus influenzae type b meningitis in rat
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Bacterial meningitis continues to be a major health problem and despite great advances in antimicrobial therapy the fatality rate remains high. There is increasing evidence that leukocyte-endothelial interactions are involved in CNS damage during bacterial meningitis. Once leukocytes have entered the CSF they cause injury by releasing toxic molecules such as nitric oxide (NO) and reactive oxygen species (ROS). The induction of iNOS was examined by assessing intracerebral mRNA expression and protein production during the course of Haemophilus influenzae type b (Hib) meningitis in the rat. Induction of iNOS mRNA was detected 12h postinoculation (pi), followed by a gradual reduction. The increased number of intracerebral iN OS expressing cells was detected at 12h pi. followed by further elevation to peak expression at 72h pi. The iNOS positive tissue also bound antibodies specific for nitrotyrosine. The expression of iNOS and NO production, as shown by nitrotyrosine expression, correlated with disease severity, suggesting that activation of iNOS may play an important role in Haemophilus irifluenzae type b meningitis.
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| 3. |
- Cedergren, Jan, et al.
(författare)
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Inducible nitric oxide synthase is expressed in synovial fluid granulocytes
- 2002
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Ingår i: Clinical Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 130, s. 150-155
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Tidskriftsartikel (refereegranskat)abstract
- The objective of the study was to evaluate the NO-producing potential of synovial fluid (SF) cells. SF from 15 patients with arthritis was compared with blood from the same individuals and with blood from 10 healthy controls. Cellular expression of inducible nitric oxide synthase (iNOS) was analysed by flow cytometry. High-performance liquid chromatography was used to measure L-arginine and L-citrulline. Nitrite and nitrate were measured colourimetrically utilizing the Griess' reaction. Compared to whole blood granulocytes in patients with chronic arthritis, a prominent iNOS expression was observed in SF granulocytes (P < 0.001). A slight, but statistically significant, increase in iNOS expression was also recorded in lymphocytes and monocytes from SF. L-arginine was elevated in SF compared to serum (257 ± 78 versus 176 ± 65 µmol/l, P = 0.008), whereas a slight increase in L-citrulline (33 ± 11 versus 26 ± 9 µmol/l), did not reach statistical significance. Great variations but no significant differences were observed comparing serum and SF levels of nitrite and nitrate, respectively, although the sum of nitrite and nitrate tended to be elevated in SF (19.2 ± 20.7 versus 8,6 ± 6.5 µmol/l,P = 0.054). Synovial fluid leucocytes, in particular granulocytes, express iNOS and may thus contribute to intra-articular NO production in arthritis.
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| 4. |
- Cedergren, Jan, et al.
(författare)
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Inducible nitric oxide synthase (NOS II) is constitutive in human neutrophils
- 2003
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Ingår i: APMIS. - : Wiley. - 0903-4641 .- 1600-0463. ; 111:10, s. 963-968
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to study the expression of inducible nitric oxide synthase (NOS II) in and NO production by human blood neutrophils and in in vivo exudated neutrophils. Cellular expression of NOS II was evaluated by flow cytometry in whole blood, in isolated blood neutrophils, and in neutrophils obtained by exudation in vivo into skin chambers. Neutrophil NOS II was also demonstrated by Western blotting. Uptake of 3H-labelled L-arginine was studied in vitro and NOS activity measured in a whole cell assay by the conversion of 3H-arginine to 3H-citrulline. In contrast to unseparated blood cells, NOS II was demonstrable both in isolated blood neutrophils and exudated cells. The failure to detect NOS II by flow cytometry in whole blood cells thus proved to be due to the quenching effect of hemoglobin. Western blotting revealed a 130 kD band corresponding to NOS II in isolated blood neutrophils, but detection was dependent on diisopropylfluorophosphate for proteinase inhibition. L-arginine was taken up by neutrophils, but enzymatic activity could not be demonstrated. We conclude that human neutrophils constitutively express NOS II, but that its demonstration by FITC-labelling is inhibited by hemoglobin-mediated quenching in whole blood samples.
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| 5. |
- Cedergren, Jan, et al.
(författare)
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Intracellular oxidative activation in synovial fluid neutrophils from patients with rheumatoid arthritis but not from other arthritis patients
- 2007
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Ingår i: Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 34:11, s. 2162-2170
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare total and intracellular oxidative activation of blood and synovial fluid (SF) neutrophils from patients with rheumatoid arthritis (RA) and other arthritides with blood donor neutrophils. Methods: Peripheral blood and SF samples were obtained from 26 gonarthritis patients (13 RA, 13 non-RA) attending the rheumatology unit for therapeutic joint aspiration. Isolated neutrophils were stimulated by a formylated tripeptide (fMLF) or by microbeads coated with collagen-I. Formation of superoxide-anion-derived reactive oxygen species (ROS) was studied by luminol-enhanced chemiluminescence. Paired samples of blood and SF neutrophils from patients with active arthritis were compared with blood neutrophils from patients in remission and from 47 healthy blood donors. Results: SF neutrophils from patients with RA, but not from non-RA patients, showed high baseline intracellular ROS production. Blood neutrophils from arthritis patients in remission existed in a primed state as revealed by more rapid oxidative response after collagen-bead challenge and a more pronounced response after fMLF stimulation compared to healthy blood donors. Blood neutrophils from RA patients with ongoing gonarthritis, however, did not differ from healthy blood donors concerning oxidative activation, whereas blood neutrophils from non-RA patients with gonarthritis showed a significantly lower peak ROS production. Conclusions: A novel finding with pathogenetic implications in our study is that SF neutrophils from patients with RA, but not other arthritides, are activated and produce ROS intracellularly. This implies that synovial neutrophils in RA are engaged in the processing of endocytosed material.
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| 6. |
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| 7. |
- Cedergren, Jan, 1965-
(författare)
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Radical aspects on arthritis : the role of neutrophil generation of nitric oxide and superoxide in inflammatory conditions
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The polymorphonuclear neutrophil granulocytes (neutrophils) are gaining renewed interest regarding their involvement in chronic inflammatory disorders, including rheumatoid arthritis (RA). Besides phagocytic and destructive capabilities, neutrophils have regulatory roles, e.g. by influencing responses from dendritic cells and lymphocytes. Several animal models have revealed that neutrophils are crucial for the initiation and maintenance of chronic inflammatory diseases. Neutrophil function is highly dependent on their ability to produce superoxide, an oxygen radical which can be further metabolized to other free radicals. Whether or not neutrophils are capable of producing the oxygen radical nitric oxide (NO˙) has been a matter of debate.In this thesis it was shown that freshly isolated neutrophils from the joint cavity of patients with RA, but not from other arthritis patients, had ongoing intracellular production of superoxide, indicating the processing of ingested material.The finding that joint neutrophils, but seemingly not circulating cells, expressed the NO-inducing enzyme iNOS, led to a series of experiments aimed to elucidate where in the exudative process this enzyme could first be detected. We could finally, for the first time, present evidence that human neutrophils actually express iNOS constitutively. Our data also suggest that neutrophil iNOS may be membrane associated, thus differing from the cytosolic location in other cell types. Since NOS activity was not demonstrated in isolated cells, the notion that neutrophil iNOS is regulated primarily at the transcriptional level must be questioned. NO production from iNOS requires the presence of its substrate, L-arginine. To test the hypothesis that neutrophil arginase prevents neutrophil NO-production, we investigated whether arginase inhibition affects neutrophil NO-dependent oxidative function. Initial data revealed a difference in the effect of arginase inhibition comparing neutrophil stimulus with a soluble formylated tri-peptide (fMLF) and integrin-mediated stimulation with particle-bound collagen type-1. This led to the hypothesis that integrin-ligation on neutrophils induces extracellular liberation of arginase, which was confirmed both by measuring arginase and its enzyme activity. The findings in this thesis may be important not only regarding the role of neutrophils in chronic joint inflammation, but also as a link in the accelerated atherosclerosis observed in chronic inflammatory disorders, e.g. RA.
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| 8. |
- Devenney, Irene, et al.
(författare)
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Urinary nitric oxide excretion in infants with eczema
- 2010
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Ingår i: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 21:1, s. e229-e234
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Tidskriftsartikel (refereegranskat)abstract
- Eczema is characterized by inflammation of the skin and is commonly associated with food allergy. It has been suggested that nitric oxide (NO) is an important player in eczema, food allergy and intestinal inflammation. The aim of this study was to assess the levels of urinary NO breakdown products in infants with eczema and the effect of eczema treatment on NO levels. Ninety-four infants with eczema, 58 boys and 36 girls, with a mean age of 7.5 ± 5.2 months (mean ± s.d.) at inclusion were examined twice with an interval of 6 wk. The sum of nitrite and nitrate was measured colorimetrically in urinary samples from both visits and compared with clinical data concerning eczema severity, nutrition, gastrointestinal symptoms, asthma and skin prick positivity. The levels of NO products increased significantly from the first to the second visit: 289; 374 μm (median; IQR) vs. 457; 678 μm (median; IQR) (p < 0.001) in parallel with a significant improvement of the eczema. After eczema treatment consisting of skin care and elimination diet during the 6-wk interval between evaluations, the NO levels approached the values previously found in healthy children. The results support previous studies indicating that the homeostasis of nitrogen radicals is disturbed in childhood eczema.
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| 9. |
- Forslund, Tony, 1956-
(författare)
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Nitric oxide modulates neutrophil function
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An important role of the neutrophils is to attack and destroy microbial intruders. In order to do so, these leukocytes must adhere to the blood vessel wall, pass through the endothelial cell layer, move through the tissues to the point of infection, ingest the intruder and destroy it.The aim of this thesis was to study the effects of nitric oxide (NO) on the different steps in the inflammatory response of the neutrophil.Adhesion to a collagen surface was decreased by pretreatment with a NO-releasing substance, and this was mimicked by pretreatment with a functional cGMP-analogue, indicating a role of the NO/cGMP pathway. Homotypic adhesion, aggregation, was not affected by external NO, but when the precursor of endogenous NO-production CLarginine) was added, the aggregation increased. Measurements of total F-actin content in cells showed that a NO-releasing substance decreased the total amount of F-actin, while cGMP increased it. Treatment with L-arginine had no effect.Phagocytosis was neither affected by endogenous NO, nor by a NO-releasing substance. However, if the prey itself released NO, both the adhesion to and phagocytosis of the target was decreased. This NO-particle also inhibited the production of oxygen metabolites, as measured using Luminal-dependent chemiluminescence. The inhibition was almost exclusively affecting the intracellular production of oxygen metabolites, as could be seen when neutrophils were stimulated with FMLP or PMA after an incubation with the NO-releasing particles.Treatment of neutrophils with the NO-releasing substance nitroprusside resulted in a decrease of the respiratory burst. It was primarily the extracellular release that was diminished. This effect can be explained by an inhibition of the enzyme producing oxygen metabolites. Endogenous NO-production increased the chemiluminescence whereas an inhibitor of the NO-synthase decreased it. A possible explanation for these effects is an NO-inhibition of the protection against hydrogen peroxide, i.e. catalase activity, resulting in an increased amount of oxygen metabolites.In conclusion, these results shows that NO has different effects depending on where it is produced and in what quantities. It modulates the different steps of the inflammatory response of neutrophils. Control of NO-formation could therefore be a way to control inflammation.
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| 10. |
- Forslund, Tony, 1956-, et al.
(författare)
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Nitric Oxide Regulates the Aggregation of Stimulated Human Neutrophils
- 2000
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 274:2, s. 482-487
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophil aggregation is mediated by both CD18 integrin and L-selectin. Nitric oxide attenuates the integrin-mediated adhesion of neutrophils to collagen and to endothelium and may therefore affect aggregation as well. FMLP-stimulated neutrophils exposed to -arginine showed increased and prolonged aggregation, whereas cells pretreated with L-NAME did not differ from FMLP-stimulated controls. Nitric oxide is known to induce ADP ribosylation of G-actin, which inhibits polymerization. We detected equivalent levels of total F-actin in cells pretreated with -arginine or L-NAME and non-pretreated controls. However, neutrophils pretreated with -arginine and stimulated by CD18 integrin cross-linking exhibited a more limited increase in total F-actin, compared to control and L-NAME-pretreated cells. Thus at least two signaling pathways may be involved FMLP-stimulated aggregation, mediated by CD18 integrins. More specifically, it is plausible that FMLP-receptor signaling upregulates CD18 integrins and endogenous NO subsequently modulates CD18-mediated signaling to prolong aggregation, possibly through ADP-ribosylation of actin.
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| 11. |
- Hollén, Elisabet, et al.
(författare)
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Urinary nitric oxide during one year of gluten-free diet with or without oats in children with coeliac disease
- 2006
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 41:11, s. 1272-1278
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Although in both adults and children with coeliac disease (CD) it is now recommended that oats be added to their gluten-free diet, there is still some controversy concerning the possible harmful effects of oats in some individuals. In this study concentrations of nitric oxide metabolites were repeatedly measured in the urine of children under investigation for CD, when on a gluten-free diet with or without oats. Material and methods. The study included 116 children, randomized to a standard gluten-free diet (GFD-std) or a gluten-free diet supplemented with wheat-free oat products (GFD-oats), over a one-year period. Small-bowel biopsy was performed at the beginning and end of the study. Morning urine samples were collected from 87 children and urinary nitrite/nitrate concentrations were monitored at 0, 3, 6, 9 and 12 months. Results. All patients were in clinical remission after the study period. There was a rapid decline in urinary nitrite/nitrate concentrations in both groups as early as after 3 months. No differences were seen between the study groups at any of the checkpoints. However, at the end of the study, the nitrite/nitrate values of 9 children in the GFD-oats group and 8 children in the GFD-std group had not normalized. Conclusions. Children with CD on a gluten-free diet with oats display a similar reduction in urinary nitrite/nitrate as those on a traditional gluten-free diet. Some children, however, still demonstrate high nitrite/nitrate excretion after one year on either diet, indicating that long-term follow-up studies of children on an oats-containing diet are needed.
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| 12. |
- Högberg, Lotta, et al.
(författare)
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Children with screening-detected coeliac disease show increased levels of nitric oxide products in urine
- 2011
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Ingår i: ACTA PAEDIATRICA. - : Blackwell Publishing Ltd. - 0803-5253 .- 1651-2227. ; 100:7, s. 1023-1027
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Increased concentration of nitric oxide (NO) metabolites, nitrite and nitrate, in the urine is a strong indication of ongoing small intestinal inflammation, which is a hallmark of the enteropathy of coeliac disease (CD). It has previously been shown that children with symptomatic, untreated CD have increased levels of NO oxidation products in their urine. The aim of this study was to investigate whether screening-detected, asymptomatic coeliac children display the same urinary nitrite/nitrate pattern. Methods: In a multicenter screening study, serum samples were collected from 7208 12-year-old children without previously diagnosed CD. Sera were analysed for anti-human tissue transglutaminase (tTG) of isotype IgA. Small bowel biopsy was performed in antibody-positive children, yielding 153 new cases of CD. In the screening-detected individuals, the sum of nitrite and nitrate concentrations in the urine was analysed and used as an indicator of NO production. For comparison, 73 children with untreated, symptomatic CD were studied. Results: The nitrite/nitrate levels in children with screening-detected CD and those with untreated symptomatic CD did not differ significantly. Both groups had significantly increased urinary nitrite/nitrate concentrations compared to the children with normal small bowel biopsy (p andlt; 0.001). Conclusion: Children with screening-detected CD have increased production of NO just as children with untreated symptomatic CD. High NO metabolite levels in the urine may indicate a pathogenetic feature of CD and be a marker of major clinical importance.
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| 13. |
- Idh, Jonna, et al.
(författare)
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Nitric oxide production in the exhaled air of patients with pulmonary tuberculosis in relation to HIV co-infection
- 2008
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Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 8:146
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Tidskriftsartikel (refereegranskat)abstract
- Background: Nitric oxide (NO) is essential for host defense in rodents, but the role of NO during tuberculosis (TB) in man remains controversial. However, earlier observations that arginine supplementation facilitates anti-TB treatment, supports the hypothesis that NO is important in the host defense against TB. Local production of NO measured in fractional exhaled air (FeNO) in TB patients with and without HIV co-infection has not been reported previously. Thus, our aim was to investigate levels of FeNO in relation to clinical symptoms and urinary NO metabolites (uNO). Methods: In a cross sectional study, FeNO and uNO were measured and clinical symptoms, chest x-ray, together with serum levels of arginine, tumor necrosis factor alpha (TNF-alpha) and interleukin 12 (IL-12) were evaluated in sputum smear positive TB patients (HIV+/TB, n = 36, HIV-/TB, n = 59), their household contacts (n = 17) and blood donors (n = 46) from Gondar University Hospital, Ethiopia. Results: The proportion of HIV-/TB patients with an increased FeNO level (> 25 ppb) was significantly higher as compared to HIV+/TB patients, but HIV+/TB patients had significantly higher uNO than HIV-/TB patients. HIV+ and HIV-/TB patients both had lower levels of FeNO compared to blood donors and household contacts. The highest levels of both uNO and FeNO were found in household contacts. Less advanced findings on chest x-ray, as well as higher sedimentation rate were observed in HIV+/TB patients as compared to HIV-/TB patients. However, no significant correlation was found between FeNO and uNO, chest x-ray grading, clinical symptoms, TNF-alpha, IL-12, arginine levels or sedimentation rate. Conclusion: In both HIV negative and HIV co infected TB patients, low levels of exhaled NO compared to blood donors and household were observed. Future studies are needed to confirm whether low levels of exhaled NO could be a risk factor in acquiring TB and the relative importance of NO in human TB.
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| 14. |
- Idh, Jonna, et al.
(författare)
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Susceptibility of Clinical Strains of Mycobacterium tuberculosis to Reactive Nitrogen Species in Activated Macrophages
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Nitric oxide (NO) is produced in macrophages by the inducible NO synthase (iNOS) upon activation by pro-inflammatory cytokines. NO has been shown to be essential for the control of Mycobacterium tuberculosis infection in murine models whereas its importance in man is not as clear. There is a lack of studies regarding the susceptibility to reactive nitrogen species (RNS) in clinical strains of M. tuberculosis and the relation to first-line drug resistance, such as to isoniazid (INH). The aim of this study was to explore susceptibility to RNS and intracellular survival of clinical strains of M. tuberculosis, with or without INH resistance. Method: Seven clinical strains of M. tuberculosis were transformed with the pSMT1-plasmid encoding Vibrio harveyi luciferase. Survival was analysed by luminometry following exposure to the NO donor DETA/NO or peroxynitrite (SIN-1). Intracellular killing was studied in murine macrophages (RAW 264.7) activated with interferon gamma (IFN-γ) and lipopolysaccharide (LPS). Results: There was a significant effect on growth control of M. tuberculosis strains upon macrophage activation, which showed variability among clinical isolates. In the cell-free system, all strains showed a dose-dependent susceptibility to DETA/NO and SIN-1, and clinical strains were in general more resistant than H37Rv to DETA/NO. INH-resistant strains with an inhA mutation were significantly more tolerant to DETA/NO than inhA wild type. Conclusion: Reactive nitrogen species inhibited growth of clinical M. tuberculosis isolates both in an intra- and extracellular model with significant difference between strains. Increased tolerance to NO was associated with isoniazid resistance mediated by inhA.
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| 15. |
- Loitto, Vesa-Matti, et al.
(författare)
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Neutrophil leukocyte motility requires directed water influx
- 2002
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Ingår i: Journal of Leukocyte Biology. - 0741-5400 .- 1938-3673. ; 71:2, s. 212-222
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Tidskriftsartikel (refereegranskat)abstract
- The ability of neutrophils to sense and move to sites of infection is essential for our defense against pathogens. For motility, lamellipodium extension and stabilization are prerequisites, but how cells form such membrane protrusions is still obscure. Using contrast-enhanced video microscopy and Transwell® assays, we show that water-selective aquaporin channels regulate lamellipodium formation and neutrophil motility. Addition of anti-aquaporin-9 antibodies, HgCl2, or tetraethyl ammonium inhibited the function(s) of the channels and blocked motility-related shape changes. On human neutrophils, aquaporin-9 preferentially localized to the cell edges, where N-formyl peptide receptors also accumulated, as assessed with fluorescence microscopy. To directly visualize water fluxes at cell edges, cells were loaded with high dilution-sensitive, self-quenching concentrations of fluorophore. In these cells, motile regions always displayed increased fluorescence compared with perinuclear regions. Our observations provide the first experimental support for motility models where water fluxes play a pivotal role in cell-volume increases accompanying membrane extensions.
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| 16. |
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| 17. |
- Petersson, Christoffer, 1973-, et al.
(författare)
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Helicobacter pylori sabA adhesin evokes a strong inflammatory response in human neutrophils which is down-regulated by the neutrophil-activating protein
- 2006
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Ingår i: Medical Microbiology and Immmunology. - : Springer Science and Business Media LLC. - 0300-8584 .- 1432-1831. ; 195:4, s. 195-206
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Tidskriftsartikel (refereegranskat)abstract
- The human pathogen Helicobacter pylori expresses two dominant adhesins; the Lewis b blood group antigen binding adhesin, BabA, and the sialic acid-binding adhesin, SabA. These adhesins recognize specific carbohydrate moieties of the gastric epithelium, i.e. the Lewis b antigen, Leb, and the sialyl-Lewis x antigen, sLex, respectively, which promote infection and inflammatory processes in the gastroduodenal tract. To assess the contribution of each of BabA, SabA and the neutrophil activating protein (HP-NAP) in a local inflammation, we investigated the traits of H. pylori mutants in their capacity to interact with and stimulate human neutrophils. We thence found that the SabA adhesin was not only the key inducer of oxidative metabolism (Unemo et al. J Biol Chem 280:15390–15397, 2005), but also essential in phagocytosis induction, as evaluated by flow cytometry, fluorescence microscopy and luminol-enhanced chemiluminescence. The napA deletion resulted in enhanced generation of reactive oxygen species and impaired adherence to the host cells. In conclusion, the SabA adhesin stimulates human neutrophils through selectin-mimicry. Interestingly, HP-NAP modulates the oxidative burst, which could tune the impact of the H. pylori infection for establishment of balanced and chronic inflammation of the gastric mucosa.
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| 18. |
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| 19. |
- Schön, Thomas, et al.
(författare)
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Effects of a food supplement rich in arginine in patients with smear positive pulmonary tuberculosis - A randomised trial
- 2011
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Ingår i: Tuberculosis. - : Elsevier. - 1472-9792 .- 1873-281X. ; 91:5, s. 370-377
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Tidskriftsartikel (refereegranskat)abstract
- In tuberculosis (TB), the production of nitric oxide (NO) is confirmed but its importance in host defense is debated. Our aim was to investigate whether a food supplement rich in arginine could enhance clinical improvement in TB patients by increased NO production. Smear positive TB patients from Gondar, Ethiopia (n = 180) were randomized to a food supplementation rich in arginine (peanuts, equivalent to 1 g of arginine/day) or with a low arginine content (wheat crackers, locally called daboqolo) during four weeks. The primary outcome was cure rate according to the WHO classification and secondary outcomes were sputum smear conversion, weight gain, sedimentation rate, reduction of cough and chest X-ray improvement as well as levels of NO in urine (uNO) or exhaled air (eNO) at two months. There was no effect of the intervention on the primary outcome (OR 1.44, 95% CI: 0.69-3.0, p = 0.39) or secondary outcomes. In the subgroup analysis according to HIV status, peanut supplemented HIV+/TB patients showed increased cure rate (83.8% (31/37) vs 53.1% (17/32), p andlt; 0.01). A low baseline eNO (andlt; 10 ppb) in HIV+/TB patients was associated with a decreased cure rate. We conclude that nutritional supplementation with a food supplement rich in arginine did not have any overall clinical effect. In the subgroup of HIV positive TB patients, it significantly increased the cure rate and as an additional finding in this subgroup, low initial levels of NO in exhaled air were associated with a poor clinical outcome but this needs to be confirmed in further studies.
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| 20. |
- Sundqvist, Tommy, et al.
(författare)
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Oral immunoglobulin treatment improved intestinal permeability in children with active Crohns disease
- 2017
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Ingår i: Acta Paediatrica. - : WILEY. - 0803-5253 .- 1651-2227. ; 106:4, s. 647-653
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Crohns disease (CD) is a chronic mucosal inflammation that affects the intestinal barrier function, for example, by altering the intestinal permeability. This pilot clinical study investigated the impact of oral human immunoglobulin (OHIG) treatment on permeability characteristics in children with active luminal Crohns disease. Methods: The study was performed at the Department of Paediatrics, Norrkoping Hospital, Sweden. Intestinal permeability was studied in three boys aged 13, 15 and 18 years with active CD, before and after a six-week treatment programme with OHIG, using different-sized polyethylene glycols as the test molecules. Three age-and sex-matched children with active CD treated with exclusive enteral nutrition (EEN) were also studied. Results: OHIG and EEN resulted in virtually similar reductions in the signs and symptoms of mucosal inflammation. However, OHIG, unlike EEN, appeared to normalise mucosal transfer leading to a normalisation of the maximum permeation of the small PEG molecules, as well as less restrictions of the larger PEG molecules. Conclusion: Our study found that OHIG appeared to normalise the mucosal barrier. This suggests that it could offer a new additional and versatile treatment for paediatric CD patients, with a minimal risk of adverse effects.
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| 21. |
- Särndahl, Eva, et al.
(författare)
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Enhanced Neutrophil Expression of Annexin-1 in Coronary Artery Disease
- 2010
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Ingår i: Metabolism. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 59:3, s. 443-440
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Tidskriftsartikel (refereegranskat)abstract
- Background: A dysregulated cortisol response in patients with stable coronary artery disease (CAD) is related to systemic inflammatory activity. Moreover, a dysfunctional activation status of neutrophils in CAD has been discussed. The anti-inflammatory actions of glucocorticoids are mediated by annexin-1 (ANXA1), a protein mainly expressed by innate immune cells. An altered expression of glucocorticoid receptors (GR) and ANXA1 has been associated with glucocorticoid resistance. Methods and Results: Salivary cortisol levels were measured in the morning and evening during 3 consecutive days in 30 CAD patients and 30 healthy individuals. The neutrophil expression of GR and ANXA1 was determined by flow cytometry. The effect of exogenous ANXA1 was determined in neutrophil stimulation assays. The patients showed a flattened diurnal cortisol pattern compared to healthy subjects, involving higher levels in the evening. The neutrophil expression of GRtotal and GRα, as well as the ratio of GRα:GRβ expression was significantly decreased in patients, whereas the GRβ expression did not differ compared to controls. The neutrophil expression of ANXA1 was significantly increased in patients. Ex vivo, ANXA1 suppressed LTB4-induced ROS production in neutrophils from patients, but not from controls. On the other hand, ANXA1 impaired the LTB4-induced up-regulation of β2-integrins in both patients and controls. Conclusion: CAD patients displayed a more flattened diurnal cortisol rhythm caused by higher cortisol levels in the evening compared to healthy subjects. Our findings indicate a chronic overactivation of the hypothalamic-pituitary-adrenal (HPA) axis but give no conclusive evidence for glucocorticoid resistance, as assessed by the neutrophil expression of GR and ANXA1. The data rather point towards an increased anti-inflammatory potential in neutrophils from patients with stable CAD.
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| 22. |
- Tapsas, Dimitrios, et al.
(författare)
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Urinary nitric oxide metabolites in children with celiac disease after long-term consumption of oats-containing gluten-free diet
- 2014
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa Healthcare. - 0036-5521 .- 1502-7708. ; 49:11, s. 1311-1317
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Oats are accepted in the gluten-free diet (GFD) for children with celiac disease (CD). Some reports have indicated, however, that not all celiac patients tolerate oats. We have previously shown that some children still have high levels of urinary nitric oxide (NO) metabolites as markers of intestinal inflammation after 1 year on GFD with oats. In this study, we measured urinary NO metabolites in CD children who had been consuming oats-containing GFD for an extended, 2-6-year period, also taking into consideration ordinary consumption of nitrite/nitrate-rich foods close to the urine sampling. Materials and Methods. Morning urinary nitrite/nitrate concentrations were measured in 188 pediatric CD patients. A questionnaire was used to elucidate factors possibly affecting the urinary levels, for example, dietary factors, asthma, or urinary tract infection. Results. Oats were consumed by 89.4% of the patients for a median time of 3 years. The median nitrite/nitrate level was 980 mu M. The majority (70.2%) who consumed oats had low levels of urinary nitrite/nitrate, that is, less than 1400 mu M, while 29.8% demonstrated high levels, that is, greater than 1400 mu M. Nitrite/nitrate-rich foods did not significantly influence the urinary concentrations. Conclusion. The urinary levels of NO metabolites revealed two subpopulations, one with high and one with low levels. The high levels could be possibly due to poor adherence to the GFD, sensitivity to oats, or some unknown factor(s). Nitrate-rich foods, asthma, or urinary tract infection did not affect the result. The elevated levels of NO metabolites could indicate mucosal inflammation and pinpoint the need of careful follow-up of children on oats-containing GFD.
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