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- Hedenstierna, Göran, 1941-, et al.
(author)
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Nitric oxide dosed in short bursts at high concentrations may protect against Covid 19.
- 2020
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In: Nitric oxide. - : Elsevier. - 1089-8603 .- 1089-8611. ; 103, s. 1-3
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Journal article (peer-reviewed)abstract
- It has long been suggested that NO may inhibit an early stage in viral replication. Furthermore, in vitro tests have shown that NO inhibits the replication cycle of severe acute respiratory syndrome coronavirus. Despite smoking being listed as a risk factor to contract Covid-19, only a low proportion of the smokers suffered from SARS-corona infection in China 2003, and from Covid-19 in China, Europe and the US. We hypothesize, that the intermittent bursts of high NO concentration in cigarette smoke may be a mechanism in protecting against the virus. Mainstream smoke from cigarettes contains NO at peak concentrations of between about 250 ppm and 1350 ppm in each puff as compared to medicinal use of no more than 80 to a maximum of 160 ppm. The diffusion of NO through the cell wall to reach the virus should be significantly more effective at the very high NO concentration in the smoke, according to classic laws of physics. The only oxide of nitrogen in the mainstream smoke is NO, and the NO2 concentration that is inhaled is very low or undetectable, and methemoglobin levels are lower in smokers than non-smokers, reasonably explained by the breaths of air in between the puffs that wash out the NO. Specialized iNO machines can now be developed to provide the drug intermittently in short bursts at high concentration dose, which would then provide both a preventative drug for those at high risk, as well as an effective treatment, without the health hazards associated with smoking.
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- Jeddi, Sajad, et al.
(author)
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Hydrogen sulfide potentiates the protective effects of nitrite against myocardial ischemia-reperfusion injury in type 2 diabetic rats
- 2022
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In: Nitric Oxide - Biology and Chemistry. - : Elsevier BV. - 1089-8603 .- 1089-8611. ; 124, s. 15-23
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Journal article (peer-reviewed)abstract
- Decreased heart levels of nitric oxide (NO) and hydrogen sulfide (H2S) in type 2 diabetes (T2D) are associated with a higher risk of mortality following ischemia-reperfusion (IR) injury. This study aimed to determine the effects of co-administration of sodium nitrite and sodium hydrosulfide (NaSH) on IR injury in the isolated heart from rats with T2D. Two-month-old male rats were divided into 5 groups (n = 7/group): Control, T2D, T2D + nitrite, T2D + NaSH, and T2D + nitrite + NaSH. T2D was induced using a high-fat diet and a single low dose streptozotocin (30 mg/kg) in intraperitoneal injection. Nitrite (50 mg/L in drinking water) and NaSH (0.28 mg/kg, daily intraperitoneal injection) were administrated for 9 weeks. At the end of the study, hemodynamic parameters were recorded, and infarct size and mRNA expression of H2S- and NO-producing enzymes were measured in the isolated hearts. Nitrite administration to rats with T2D improved recovery of left ventricular developed pressure (LVDP) and the peak rates of positive and negative changes in LV pressure (±dp/dt) by 30%, 17%, and 7.9%, respectively, and decreased infarct size by 18.4%. Co-administration of nitrite and NaSH resulted in further improve in recovery of LVDP, +dp/dt, and –dp/dt by 8.3% (P = 0.0478), 8.4% (P = 0.0085), and 9.0% (P = 0.0004), respectively, and also further decrease in infarct size by 24% (P = 0.0473). Nitrite treatment decreased inducible and neuronal NO synthases (iNOS, 0.4-fold; nNOS, 0.4-fold) and cystathionine β-synthase (CBS, 0.1-fold) expression in the isolated heart from rats with T2D. Co-administration of nitrite and NaSH further increased cystathionine γ-lyase (CSE, 2.8-fold) and endothelial NOS (eNOS, 2.0-fold) expression and further decreased iNOS (0.4-fold) expression. In conclusion, NaSH at a low dose potentiates the favorable effects of inorganic nitrite against myocardial IR injury in a rat model of T2D. These anti-ischemic effects, following co-administration of nitrite and NaSH, were associated with higher CSE-derived H2S and eNOS-derived NO as well as lower iNOS-derived NO in the diabetic hearts.
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- Krantz, Christina, et al.
(author)
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Nasal nitric oxide in relation to asthma characteristics in a longitudinal asthma cohort study
- 2021
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In: Nitric oxide. - : Elsevier. - 1089-8603 .- 1089-8611. ; 106, s. 1-8
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Cross-sectional studies report relations between low nasal nitric oxide (nNO) and poor asthma control and between low nNO and chronic rhinosinusitis (CRS). In our cohort study, we studied if changes in nNO related to changes in asthma control, symptoms of CRS, or asthma or rhinitis medication.METHODS: A total of 196 subjects with predominantly mild to moderate asthma, aged 10-35 years, performed nNO measurements at both baseline and follow-up after a median of 43 (range 23-65) months. Asthma control, CRS symptoms, and medication, were questionnaire-assessed at both timepoints. IgE sensitisation against aeroallergens was quantified at baseline.RESULTS: There was an increase in nNO between baseline and follow-up (764 ± 269 ppb vs. 855 ± 288 ppb, p < 0.001). When adjusted for covariates, a larger increase in nNO was found in subjects sensitised to perennial aeroallergens than those not sensitised (92 (16-167) ppb), as well as in subjects with daily use of inhaled corticosteroids (ICS) at baseline but not at follow-up than those on ICS daily at both timepoints (146 (51-242) ppb). In the same model, subjects using nasal steroids daily at both timepoints had decreased nNO compared with those without such treatment at both timepoints (-185 (-321-(-48)) ppb). No relations between changes in nNO levels and changes in asthma control or symptoms of CRS were found.CONCLUSION: Longitudinal changes in nNO were not related to changes in asthma control, but were related to changes in asthma or rhinitis medication.
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- Timby, Niklas, et al.
(author)
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Effects of age, sex and diet on salivary nitrate and nitrite in infants
- 2020
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In: Nitric oxide. - : Elsevier. - 1089-8603 .- 1089-8611. ; 94, s. 73-78
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Journal article (peer-reviewed)abstract
- The inorganic anions nitrate and nitrite are oxidation products from endogenous nitric oxide (NO) generation and constituents in our diet. A nitrate-nitrite-NO pathway exists in which nitrate can be serially reduced to bioactive NO. The first step of this pathway occurs in the oral cavity where oral bacteria convert salivary nitrate to nitrite, whereafter nitrite is reduced to NO systemically by several enzymatic and non-enzymatic pathways. Data are scarce regarding salivary levels and oral conversion capacity of these anions in infants. We measured salivary nitrate and nitrate in infants at 4 and 12 months of age and related values to age, sex, dietary pattern and oral microbiome. Saliva was collected from a total of 188 infants at 4 and 12 months of age. Salivary nitrate, nitrite and nitrite/nitrate ratio as a measure of oral nitrate-reducing capacity were analyzed by HPLC and related to age, sex, type of diet (breast milk or formula) and oral microbiome. There was no difference in salivary nitrate, nitrite or nitrite/nitrate ratio between boys and girls at any age. At 4 months levels of these parameters were lower than what has been described in adults but they had all increased significantly at 12 months of age. At 4 months of age salivary nitrite/nitrate ratio was lower in breast-fed compared to formula-fed infants, but these differences disappeared at 12 months. Several bacterial species were associated with oral nitrate reducing capacity including Prevotella, Veillonella, Alloprevotella and Leptotrichia. We conclude that in infants there is an increase in salivary nitrate and nitrite as well as in oral nitrate-reductase capacity during the first year of life. Differences observed at 4 months of age between breast-fed and formula-fed infants disappear at one year of age.
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- Zaigham, Suneela, et al.
(author)
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An observational analysis on the influence of parental allergic rhinitis, asthma and smoking on exhaled nitric oxide in offspring
- 2024
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In: Nitric oxide. - : Elsevier. - 1089-8603 .- 1089-8611. ; 149, s. 60-66
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Journal article (peer-reviewed)abstract
- BACKGROUND: Parental allergic diseases and smoking influence respiratory disease in the offspring but it is not known whether they influence fractional exhaled nitric oxide (FeNO) in the offspring. We investigated whether parental allergic diseases, parental smoking and FeNO levels in parents were associated with FeNO levels in their offspring.METHODS: We studied 609 offspring aged 16-47 years from the Respiratory Health in Northern Europe, Spain and Australia generation (RHINESSA) study with parental information from the Respiratory Health in Northern Europe (RHINE) III study and the European Community Respiratory Health Survey (ECRHS) III. Linear regression models were used to assess the association between offspring FeNO and parental FeNO, allergic rhinitis, asthma and smoking, while adjusting for potential confounding factors.RESULTS: Parental allergic rhinitis was significantly associated with higher FeNO in the offspring, both on the paternal and maternal side (percent change: 20.3 % [95%CI 5.0-37.7], p = 0.008, and 13.8 % [0.4-28.9], p = 0.043, respectively). Parental allergic rhinitis with asthma in any parent was also significantly associated with higher offspring FeNO (16.2 % [0.9-33.9], p = 0.037). However, parental asthma alone and smoking were not associated with offspring FeNO. Parental FeNO was not associated with offspring FeNO after full adjustments for offspring and parental factors.CONCLUSIONS: Parental allergic rhinitis but not parental asthma was associated with higher levels of FeNO in offspring. These findings suggest that parental allergic rhinitis status should be considered when interpreting FeNO levels in offspring beyond childhood.
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- Engel, Jörgen, 1942, et al.
(author)
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Ghrelin activates the mesolimbic dopamine system via nitric oxide associated mechanisms in the ventral tegmental area
- 2023
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In: Nitric Oxide-Biology and Chemistry. - : Elsevier BV. - 1089-8603. ; 131, s. 1-7
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Journal article (peer-reviewed)abstract
- Besides enhanced feeding, the orexigenic peptide ghrelin activates the mesolimbic dopamine system to cause reward as measured by locomotor stimulation, dopamine release in nucleus accumbens shell (NAcS), and conditioned place preference.Although the ventral tegmental area (VTA) appears to be a central brain region for this ghrelin-reward, the underlying mechanisms within this area are unknown. The findings that the gaseous neurotransmitter nitric oxide (NO) modulate the ghrelin enhanced feeding, led us to hypothesize that ghrelin increases NO levels in the VTA, and thereby stimulates reward-related behaviors. We initially demonstrated that inhibition of NO synthesis blocked the ghrelin-induced activation of the mesolimbic dopamine system. We then established that antagonism of downstream signaling of NO in the VTA, namely sGC, prevents the ability of ghrelin to stimulate the meso-limbic dopamine system. The association of ghrelin to NO was further strengthened by in vivo electrochemical recordings showing that ghrelin enhances the NO release in the VTA. Besides a GABAB-receptor agonist, known to reduce NO and cGMP, blocks the stimulatory properties of ghrelin. The present series of experiments reveal that ablated NO signaling, through pharmacologically inhibiting the production of NO and/or cGMP, prevents the ability of ghrelin to induced reward-related behaviors.
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