| 51. |
- Hansson, Magnus, et al.
(författare)
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Bioengineering and Semisynthesis of an Optimized Cyclophilin Inhibitor for Treatment of Chronic Viral Infection.
- 2015
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Ingår i: Chemistry and Biology. - : Elsevier BV. - 1879-1301 .- 1074-5521. ; 22:2, s. 285-292
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Tidskriftsartikel (refereegranskat)abstract
- Inhibition of host-encoded targets, such as the cyclophilins, provides an opportunity to generate potent high barrier to resistance antivirals for the treatment of a broad range of viral diseases. However, many host-targeted agents are natural products, which can be difficult to optimize using synthetic chemistry alone. We describe the orthogonal combination of bioengineering and semisynthetic chemistry to optimize the drug-like properties of sanglifehrin A, a known cyclophilin inhibitor of mixed nonribosomal peptide/polyketide origin, to generate the drug candidate NVP018 (formerly BC556). NVP018 is a potent inhibitor of hepatitis B virus, hepatitis C virus (HCV), and HIV-1 replication, shows minimal inhibition of major drug transporters, and has a high barrier to generation of both HCV and HIV-1 resistance.
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| 52. |
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| 53. |
- Inghammar, Malin, et al.
(författare)
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COPD and the risk of tuberculosis--a population-based cohort study.
- 2010
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Both chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) primarily affect the lungs and are major causes of morbidity and mortality worldwide. COPD and TB have common risk factors such as smoking, low socioeconomic status and dysregulation of host defence functions. COPD is a prevalent co-morbid condition, especially in elderly with TB but in contrast to other diseases known to increase the risk of TB, relatively little is known about the specific relationship and impact from COPD on TB-incidence and mortality. METHODS AND FINDINGS: All individuals > or = 40 years of age, discharged with a diagnosis of COPD from Swedish hospitals 1987-2003 were identified in the Swedish Inpatient Register (n = 115,867). Records were linked to the Swedish Tuberculosis Register 1989-2007 and the relative risk of active TB in patients with COPD compared to control subjects randomly selected from the general population (matched for sex, year of birth and county of residence) was estimated using Cox regression. The analyses were stratified by year of birth, sex and county of residence and adjusted for immigration status, socioeconomic status (SES) and inpatient co-morbidities previously known to increase the risk of TB. COPD patients had a three-fold increased hazard ratio (HR) of developing active TB (HR 3.0 (95% confidence interval 2.4 to 4.0)) that was mainly dependent on an increased risk of pulmonary TB. In addition, logistic regression estimates showed that COPD patients who developed active TB had a two-fold increased risk of death from all causes within first year after the TB diagnosis compared to the general population control subjects with TB (OR 2.2, 95% confidence interval 1.2 to 4.1). CONCLUSIONS: This population-based study comprised of a large number of COPD patients shows that these patients have an increased risk of developing active TB compared to the general population. The results raise concerns that the increasing global burden of COPD will increase the incidence of active TB. The underlying contributory factors need to be disentangled in further studies.
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| 54. |
- Karlsson, Michael, et al.
(författare)
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Brain mitochondrial function in a murine model of cerebral malaria and the therapeutic effects of rhEPO.
- 2013
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Ingår i: International Journal of Biochemistry and Cell Biology. - : Elsevier BV. - 1878-5875 .- 1357-2725. ; 45:1, s. 5-151
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral malaria (CM) is a life-threatening complication of Plasmodium falciparum infection. The pathogenesis of CM is complex. Cerebral metabolic dysfunction is implicated in CM, which may be caused by both an impaired cerebral microcirculation and a dysregulated inflammatory response affecting cellular respiration of mitochondria. Recombinant human erythropoietin (rhEPO) is a promising new therapy that has been shown to reduce mortality in a mouse model of CM. In order to further elucidate the metabolic dysfunction in CM the objective of the present study was to assess brain mitochondrial respiratory function in CM with and without rhEPO treatment. The P. berghei ANKA - C57BL/6 murine model of CM was used. Mitochondrial respiration was analyzed in brain homogenates using high-resolution respirometry and a multiple substrate and inhibitor protocol. The animals were divided into four groups; infected injected with saline or with rhEPO, non-infected injected with saline or with rhEPO. Infected mice developed CM and treatment with rhEPO attenuated clinical signs of disease. There were no differences in respiratory parameters of brain mitochondria between infected and non-infected mice and no connection between disease severity and mitochondrial respiratory function. Treatment with rhEPO similarly had no effect on respiratory function. Thus cerebral metabolic dysfunction in CM does not seem to be directly linked to altered mitochondrial respiratory capacity as analyzed in brain homogenates ex vivo. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.
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| 55. |
- Kisiel, Marta A., 1984-, et al.
(författare)
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Inflammatory bowel disease and asthma. Results from the RHINE study
- 2023
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Ingår i: Respiratory Medicine. - : Elsevier. - 0954-6111 .- 1532-3064. ; 216
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Tidskriftsartikel (refereegranskat)abstract
- Background: Asthma and inflammatory bowel disease (IBD) are common inflammatory diseases. The aim of this study was to investigate the associations of IBD with asthma and respiratory symptoms. Methods: This study is based on 13,499 participants from seven northern European countries that filled in a postal questionnaire on asthma, respiratory symptoms, IBD including ulcerative colitis and Crohn's disease and various lifestyle variables. Results: There were 195 participants with IBD. The prevalence of asthma (14.5 vs 8.1%, p = 0.001), different respiratory symptoms (range 11.9-36.8% vs range 6.0-18.6%, p < 0.005), non-infectious rhinitis (52.1 vs. 41.6%, p = 0.004) and chronic rhinosinusitis (11.6 vs 6.0%, p = 0.001) were higher in subjects with IBD than in those without IBD. In multivariable regression analysis, the association between IBD and asthma was statistically significant (OR 1.95 (95% CI 1.28-2.96)) after adjusting for confounders such as sex, BMI, smoking history, educational level and physical activity. There was a significant association between asthma and ulcerative colitis (adjusted OR 2.02 (95% CI 1.27-2.19)), and asthma but not Crohn's disease (adjusted OR 1.66 (95% CI 0.69-3.95)). A significant gender interaction was found with a significant association between IBD and asthma in women but not in men ((OR 2.72 (95% CI 1.67-4.46) vs OR 0.87 (95% CI 0.35-2.19), p = 0.038). Conclusions: Patients with IBD, particularly those with ulcerative colitis and female, have a higher prevalence of asthma and respiratory symptoms. Our findings indicate that it is important to consider respiratory symptoms and disorders when examining patients with manifest or suspected IBD.
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| 56. |
- Labor, Marina, et al.
(författare)
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Regular Inhaled Corticosteroids Use May Protect Against Severe COVID-19 Outcome in COPD
- 2023
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Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - : DOVE MEDICAL PRESS LTD. - 1176-9106 .- 1178-2005. ; 18, s. 1701-12
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Population-based studies provide conflicting evidence about how inhaled corticosteroids (ICS) impact COVID-19 outcomes among COPD patients. We investigated whether regular ICS exposure affects risk, severity, or survival in SARS-CoV-2 infection, using a nationwide linked Swedish population register database. Patients and Methods: During January–December 2020, we studied two defined Swedish adult populations – Whole population [≥ 40 years] (N = 5243479), and COPD subpopulation [≥ 40 years] (N = 133372), in three study cohorts, respectively: 1. Overall cohort (index date 1 Jan 2020), 2. COVID-19 diagnosed sub-cohort (index date = diagnosis date), and 3. COVID-19 hospitalized sub-cohort (index date = admission date). Regular exposure was defined as ≥ 3 ICS prescriptions in the year before index. Hazard ratios (HRs) for outcomes (COVID-19 onset, hospitalization, ICU admission, or death) related to ICS exposure were estimated using Cox regression. Confounding was controlled by propensity score methods applying Average Treatment effect in the Treated (ATT) weighting. Results: Regular ICS use was associated with only very slightly increased onset of COVID-19, hospitalization, ICU admission, and death in the overall whole population cohort and in the overall COPD subpopulation cohort, except for ICU admission (marginally non-significant HRs, up to 1.13); and no clear increase in the diagnosed sub-cohorts. However, in the COVID-19 hospitalized COPD sub-cohort, ICS therapy showed reduced risks against progression to ICU admission and death, significant for death (HR 0.82 95% CI [0.67– 0.99]). Conclusion: For COPD patients, ICS therapy offers some protection against progression to ICU admission and death among COVID-19 hospitalized patients. Our findings alleviate concerns about increased risks of COVID-19 by ICS treatment and provide evidence supporting the continuation of ICS therapy for COPD patients.
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| 57. |
- Landén, Mikael, 1966, et al.
(författare)
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Respiratory infections during lithium and valproate medication: a within-individual prospective study of 50,000 patients with bipolar disorder
- 2021
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Ingår i: International Journal of Bipolar Disorders. - : Springer Science and Business Media LLC. - 2194-7511. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Background In vitro studies have demonstrated that lithium has antiviral properties, but evidence from human studies is scarce. Lithium is used as a mood stabilizer to treat patients with bipolar disorder. Here, the aim was to investigate the association between lithium use and the risk of respiratory infections in patients with bipolar disorder. To rule out the possibility that a potential association could be due to lithium's effect on psychiatric symptoms, we also studied the effect of valproate, which is an alternative to lithium used to prevent mood episodes in bipolar disorder. Method We followed 51,509 individuals diagnosed with bipolar disorder in the Swedish Patient register 2005-2013. We applied a within-individual design using stratified Cox regression to estimate the hazard ratios (HRs) of respiratory infections during treated periods compared with untreated periods. Results During follow-up, 5,760 respiratory infections were documented in the Swedish Patient Register. The incidence rate was 28% lower during lithium treatment (HR 0.73, 95% CI 0.61-0.86) and 35% higher during valproate treatment (HR 1.35, 95% CI 1.06-1.73) compared with periods off treatment. Conclusions This study provides real-world evidence that lithium is associated with decreased risk for respiratory infections and suggests that the repurposing potential of lithium for potential antiviral or antibacterial effects is worthy of investigation.
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| 58. |
- Leander, Mai, et al.
(författare)
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Impact of anxiety and depression on respiratory symptoms
- 2014
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 108:11, s. 1594-1600
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Tidskriftsartikel (refereegranskat)abstract
- Psychological factors such as anxiety and depression are prevalent in patients with asthma. The purpose of this study was to investigate the relationship between respiratory symptoms and psychological status and to estimate the importance of psychological status in comparison with other factors that are known to be associated with respiratory symptoms. This study included 2270 subjects aged 20-44 (52% female) from Sweden, Iceland, and Norway. Each participant underwent a clinical interview including questions on respiratory symptoms. Spirometry and methacholine challenge were performed. Symptoms of depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS). Eighty-two percent of the subjects reported no anxiety or depression whatsoever, 11% reported anxiety, 2.5% depression and 4% reported both anxiety and depression. All respiratory symptoms, such as wheezing, breathlessness and nightly symptoms, were more common, at a statistically significant level, in participants who had depression and anxiety, even after adjusting for confounders (ORs 1.33-1.94). The HADS score was the most important determinant for nightly symptoms and attacks of breathlessness when at rest whereas bronchial responsiveness was the most important determinant for wheezing, and breathlessness when wheezing. The probability of respiratory symptoms related to HADS score increased with increasing HADS score for all respiratory symptoms. In conclusion, there is a strong association between respiratory symptoms and psychological status. There is therefore a need for interventional studies designed to improve depression and anxiety in patients with respiratory symptoms. (C) 2014 Elsevier Ltd. All rights reserved.
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| 59. |
- Lim, Eric, et al.
(författare)
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Longitudinal study of the profile and predictors of left ventricular mass regression after stentless aortic valve replacement
- 2008
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Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 0003-4975 .- 1552-6259. ; 85:6, s. 2026-2029
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study was to evaluate the long-term profile and determine the factors that would influence the effect and rate of ventricular mass regression with time after aortic valve replacement with a stentless or a homograft valve.METHODS: We studied 300 patients during a 10-year period with at least a year of follow-up with a total of 1,273 serial echocardiographic measurements. Left ventricular mass was calculated from M-mode recordings and indexed to body surface area. Longitudinal data analysis was performed using a linear mixed effects model.RESULTS: The mean age (+/- standard deviation) was 65 (+/-14) years, consisting of 216 (72%) males. A stentless valve was implanted in 156 (52%), and a homograft in 144 (48%). The median time (interquartile range) to follow-up was 4.7 (2.8 to 6.6) years. The greatest rate of left ventricular mass regression occurred in the first year after surgery. On multivariable modeling, independent predictors of left ventricular mass were valve size (p = 0.011), left ventricular function (moderate impairment, p = 0.418; severe impairment, p = 0.011), and baseline left ventricular mass (middle tercile, p < 0.001; highest tercile, p < 0.001). Only baseline ventricular mass influenced the rate of subsequent left ventricular mass regression; the greatest rate of regression occurred in patients with the highest baseline values of ventricular mass (p < 0.001).CONCLUSIONS: The greatest rate of left ventricular mass regression occurs in the first year with baseline left ventricular mass as the strongest predictor and the only identified variable that influenced the rate of left ventricular mass regression.
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| 60. |
- Lindgren, Arne, et al.
(författare)
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Electrocardiographic changes in stroke patients without primary heart disease
- 1994
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Ingår i: Clinical Physiology. - 1365-2281. ; 14:2, s. 223-231
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Tidskriftsartikel (refereegranskat)abstract
- Consecutive electrocardiograms were recorded in 28 stroke patients without signs of primary heart disease. Individuals with subarachnoidal haemorrhage, or electrolyte disturbances were excluded. A computerized tomography of the brain was performed in each case and showed a cerebral haemorrhage (n = 4), cortical infarction (n = 6), subcortical infarction (n = 14) and normal finding (n = 4). One patient developed atrial fibrillation but no other case of serious disturbances in rate of rhythm occurred. None developed AV block, bundle branch blocks or significant changes in QRS complexes. The most common abnormalities in ECG were transient STT changes in lateral leads, which were seen in 13 cases. The typical findings were flat or slightly negative T waves, horizontal or down-sloping ST segments and sometimes a small ST depression. In no case did ECG show typical signs of acute myocardial infarction. A transient prolonged QT interval was seen in three patients and transient U waves in four. ECG did not correlate to the location of the vascular lesion seen on CT or the clinical outcome. It is concluded that STT changes of a small magnitude are seen in about half of the cases of stroke patients without primary heart disease and that they do not resemble the typical pattern of acute myocardial ischaemia.
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