| 1. |
- Albayaty, Muna, et al.
(författare)
-
Pharmacokinetic Evaluation of Once-Weekly and Once-Monthly Buprenorphine Subcutaneous Injection Depots (CAM2038) Versus Intravenous and Sublingual Buprenorphine in Healthy Volunteers Under Naltrexone Blockade : An Open-Label Phase 1 Study
- 2017
-
Ingår i: Advances in Therapy. - : Springer Science and Business Media LLC. - 0741-238X .- 1865-8652. ; 34:2, s. 560-575
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: CAM2038 q1w (once weekly) and q4w (once monthly) are investigational buprenorphine subcutaneous (SC) formulations based on FluidCrystal® injection depot technology. These two drug products are being developed for opioid dependence treatment, with a target for once-weekly and once-monthly SC dosing. The rationale for developing two products with different dosing frequencies is that treatment strategies/routines, and hence different treatment preferences, can vary between patients, different stages of opioid maintenance treatment, and countries. This study evaluated the pharmacokinetics and safety of buprenorphine and norbuprenorphine following administration of CAM2038 q1w or q4w versus active controls. Methods: Healthy volunteers were randomized to five treatment groups. All received a single intravenous dose of buprenorphine 600 µg, followed post-washout by a single dose of CAM2038 q4w 96 mg, a single dose of CAM2038 q4w 192 mg, or sublingual buprenorphine 8, 16, or 24 mg daily for 7 days, followed post-washout by a single dose of CAM2038 q4w 64 or 128 mg or four repeated weekly doses of CAM2038 q1w 16 mg. All subjects received daily naltrexone. Results: Eighty-seven subjects were randomized. Median buprenorphine tmax after CAM2038 q4w was 4–10 h (24 h for CAM2038 q1w); mean terminal half-life was 19–25 days (5 days for CAM2038 q1w). CAM2038 q4w showed dose-proportional buprenorphine release, with similar exposure to repeat-dose CAM2038 q1w at comparable monthly dose level. Both CAM2038 formulations showed complete absolute bioavailability of buprenorphine and 5.7- to 7.7-fold greater buprenorphine bioavailability versus sublingual buprenorphine. CAM2038 q1w and q4w were well tolerated; subjects’ acceptance was higher for CAM2038 than for sublingual buprenorphine 1 h post-dose. Conclusions: The pharmacokinetic profiles of CAM2038 q1w and q4w versus sublingual buprenorphine support expected treatment efficacy with once-weekly and once-monthly dosing, respectively. CAM2038 formulations were safe and showed good local tolerability. Trial registration: ISRCTN24987553. Funding: Camurus AB.
|
|
| 2. |
- Andersson, Anders, et al.
(författare)
-
Effects of Tobacco Smoke on IL-16 in CD8+ Cells from Human Airways and Blood: a Key Role for Oxygen Free Radicals?
- 2011
-
Ingår i: AJP - Lung cellular and molecular physiology. - : American Physiological Society. - 1522-1504. ; 300:1
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic exposure to tobacco smoke leads to an increase in the frequency of infections and in CD8(+) and CD4(+)cells as well as the CD4(+) chemo-attractant cytokine IL-16 in the airways. Here, we investigated whether tobacco smoke depletes intracellular IL-16 protein and inhibits de novo production of IL-16 in CD8(+) cells from human airways and blood, while at the same time increasing extracellular IL-16 and whether oxygen free radicals (OFR) are involved. Intracellular IL-16 protein in CD8(+) cells and mRNA in all cells was decreased in bronchoalveolar lavage (BAL) samples from chronic smokers. This was also the case in human blood CD8(+) cells exposed to water-soluble tobacco smoke components in vitro; in which oxidized proteins were markedly increased. Extracellular IL-16 protein was increased in cell-free BAL fluid from chronic smokers and in human blood CD8(+) cells exposed to water-soluble tobacco smoke components in vitro. This was not observed in occasional smokers after short-term exposure to tobacco smoke. A marker of activation (CD69) was slightly increased whereas other markers of key cellular functions (membrane integrity, apoptosis and proliferation) in human blood CD8(+) cells in vitro were negatively affected by water-soluble tobacco smoke components. An OFR scavenger prevented these effects whereas a protein synthesis inhibitor, a beta-adrenoceptor, a glucocorticoid receptor agonist, a phosphodiesterase, a calcineurin phosphatase and a caspase-3 inhibitor did not. In conclusion, tobacco smoke depletes preformed intracellular IL-16 protein, inhibits its de novo synthesis and distorts key cellular functions in human CD8(+) cells. OFR may play a key role in this context.
|
|
| 3. |
- Andersson, Anders, et al.
(författare)
-
Impact of tobacco smoke on interleukin-16 protein in human airways, lymphoid tissue and T lymphocytes
- 2004
-
Ingår i: Clinical and experimental immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 138:1, s. 75-82
-
Tidskriftsartikel (refereegranskat)abstract
- CD4(+) and CD8(+) lymphocytes are mobilized in severe chronic obstructive pulmonary disease (COPD) and the CD8(+) cytokine interleukin (IL)-16 is believed to be important in regulating the recruitment and activity of CD4(+) lymphocytes. In the current study, we examined whether tobacco smoke exerts an impact not only on IL-16 in the lower airways but also in CD4(+) or CD8(+) lymphocytes or in lymphoid tissue. The concentration of IL-16 protein was measured by enzyme-linked immunosorbent assay (ELISA) in concentrated bronchoalveolar lavage fluid (BALF) collected from 33 smokers with chronic bronchitis (CB), eight asymptomatic smokers (AS) and seven healthy never-smokers (NS). The concentrations of IL-16 and soluble IL-2 receptor alpha (sIL-2Ralpha) protein were also measured in conditioned medium from human blood CD4(+) and CD8(+) lymphocytes stimulated with tobacco smoke extract (TSE) in vitro. IL-16 mRNA was assessed in vitro as well, using reverse transcription-polymerase chain reaction (RT-PCR). Finally, the intracellular immunoreactivity for IL-16 protein (IL-16IR) was assessed in six matched pairs of palatine tonsils from smokers and non-smokers. BALF IL-16 was higher in CB and AS than in NS. TSE substantially increased the concentration of IL-16 but not sIL-2Ralpha in conditioned medium from CD4(+) and CD8(+) lymphocytes. There was no corresponding effect on IL-16 mRNA. IL-16IR in tonsils was lower in smokers than in non-smokers. The current findings demonstrate that tobacco smoke exerts a wide impact on the CD8(+) cytokine IL-16, in the airway lumen, in blood CD4(+) and CD8(+) lymphocytes and in lymphoid tissue. The effect on IL-16 release may be selective for preformed IL-16 in CD4(+) lymphocytes. New clinical studies are required to evaluate whether tobacco smoke mobilizes T lymphocytes via IL-16 in the lower airways and whether this mechanism can be targeted in COPD.
|
|
| 4. |
- Andersson, Anders, et al.
(författare)
-
Interleukin-16-producing NK cells and T-cells in the blood of tobacco smokers with and without COPD
- 2016
-
Ingår i: International Journal of Chronic Obstructive Pulmonary Disease. - : Informa UK Limited. - 1178-2005. ; 11, s. 2245-2258
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Long-term exposure to tobacco smoke causes local inflammation in the airways that involves not only innate immune cells, including NK cells, but also adaptive immune cells such as cytotoxic (CD8(+)) and helper (CD4(+)) T-cells. We have previously demonstrated that long-term tobacco smoking increases extracellular concentration of the CD4(+)-recruiting cytokine interleukin (IL)-16 locally in the airways. Here, we hypothesized that tobacco smoking alters IL-16 biology at the systemic level and that this effect involves oxygen free radicals (OFR). Methods: We quantified extracellular IL-16 protein (ELISA) and intracellular IL-16 in NK cells, T-cells, B-cells, and monocytes (flow cytometry) in blood samples from long-term tobacco smokers with and without chronic obstructive pulmonary disease (COPD) and in never-smokers. NK cells from healthy blood donors were stimulated with water-soluble tobacco smoke components (cigarette smoke extract) with or without an OFR scavenger (glutathione) in vitro and followed by quantification of IL-16 protein. Results: The extracellular concentrations of IL-16 protein in blood did not display any substantial differences between groups. Notably, intracellular IL-16 protein was detected in all types of blood leukocytes. All long-term smokers displayed a decrease in this IL-16 among NK cells, irrespective of COPD status. Further, both NK and CD4(+) T-cell concentrations displayed a negative correlation with pack-years. Moreover, cigarette smoke extract caused release of IL-16 protein from NK cells in vitro, and this was not affected by glutathione, in contrast to the decrease in intracellular IL-16, which was prevented by this drug. Conclusion: Long-term exposure to tobacco smoke does not markedly alter extracellular concentrations of IL-16 protein in blood. However, it does decrease the intracellular IL-16 concentrations in blood NK cells, the latter effect involving OFR. Thus, long-term tobacco smoking exerts an impact at the systemic level that involves NK cells; innate immune cells that are critical for host defense against viruses and tumors-conditions that are over-represented among smokers.
|
|
| 5. |
- Bergstrand, Sara, et al.
(författare)
-
Blood flow measurements at different depths using photoplethysmography and laser Doppler techniques
- 2009
-
Ingår i: Skin research and technology. - : Wiley-Blackwell. - 0909-752X .- 1600-0846. ; 15:2, s. 139-147
-
Tidskriftsartikel (refereegranskat)abstract
- Background/purpose: This study has evaluated a multi-parametric system combining laser Doppler flowmetry and photoplethysmography in a single probe for the simultaneous measurement of blood flow at different depths in the tissue. This system will be used to facilitate the understanding of pressure ulcer formation and in the evaluation of pressure ulcer mattresses.Methods: The blood flow in the tissue over the sacrum was measured before, during and after loading with 37.5 mmHg, respectively, 50.0 mmHg. The evaluation of the system consisted of one clinical part, and the other part focusing on the technicalities of the probe prototype.Results: An increase in blood flow while loading was the most common response, but when the blood flow decreased during loading it was most affected at the skin surface and the blood flow responses may be different due to depths of measurement. Reactive hyperaemia may occur more frequently in the superficial layers of the tissue.Conclusion: The study showed that the new system is satisfactory for measuring tissue blood flow at different depths. The laser Doppler complements the photoplethysmography, and further development of the system into a thin flexible probe with the ability to measure a larger area is required.
|
|
| 6. |
- Bergstrand, Sara, et al.
(författare)
-
Existence of Tissue Blood Flow in Response to External Pressure in the Sacral Region of Elderly Individuals - Using an Optical Probe Prototype
- 2010
-
Ingår i: MICROCIRCULATION. - : Taylor and Francis. - 1073-9688 .- 1549-8719. ; 17:4, s. 311-319
-
Tidskriftsartikel (refereegranskat)abstract
- Pandgt;Objective: The aim was to investigate the existence of sacral tissue blood flow at different depths in response to external pressure and compression in elderly individuals using a newly developed optical probe prototype. Methods: The tissue blood flow and tissue thickness in the sacral area were measured during load in 17 individuals using laser Doppler flowmetry and photoplethysmography in a combined probe, and digital ultrasound. Results: The mean age was 68.6 +/- 7.0 years. While loading, the mean compression was 60.3 +/- 11.9%. The number of participants with existing blood flow while loading increased with increased measurement depth. None had enclosed blood flow deep in the tissue and at the same time an existing more superficial blood flow. Correlation between tissue thickness and BMI in unloaded and loaded sacral tissue was shown: r = 0.68 (P = 0.003) and r = 0.68 (P = 0.003). Conclusions: Sacral tissue is highly compressed by external load. There seems to be a difference in responses to load in the different tissue layers, as occluded blood flow in deeper tissue layers do not occur unless the blood flow in the superficial tissue layers is occluded.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Brunnberg, Elinor, 1948-, et al.
(författare)
-
Att höra eller nästan inte höra : Liv & hälsa ung 2005 och 2007 i Örebro län
- 2009
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I linje med FN:s barnkonvention och Konventionen om rättigheter förpersoner med funktionshinder ska ungdomars röst göras hörd. Den härrapporten bygger helt på ungdomars uppgifter om sin verklighet.Studierna Liv & hälsa ung 2005 och 2007 visar att i den reguljära skolanupplever drygt fem procent av eleverna att de har ett funktionshinder närdet gäller hörseln och de rapporterar ofta en utsatt situation. Det finns även hörselskadade ungdomar på specialskolan/riksgymnasiet för döva och hörselskadade. De hörselskadade ungdomarna är en grupp som rapporterar en mängd hälsorelaterade problem, många känner sig mobbade av kamrater eller kränkta av vuxna i skolan. Det är också en grupp som förhållandevis ofta rapporterar bruk av alkohol, tobak och narkotika. De kan även ha andra funktionsnedsättningar eller tinnitus. De hörselskadade ungdomarna är en högriskgrupp som behöver uppmärksammas och få ett bättre anpassat stöd. Det behövs fördjupade studier hur stödet kan utformas på ett relevant sätt, speciellt gäller det dem med flera funktionshinder. För att göra detta är det viktigt att ungdomarna själva involveras i arbetet. Fördjupade studier behövs också om hur hörselskadade ungdomars delaktighet i den reguljära skolan kan förbättras samt om vad som skapar exempelvis stress, trötthet och olyckor. Det behövs åtgärder för att minska den mobbning som sker och inte minst minska det ungdomar rapporterar om kränkning från vuxna. Det behövs riktade insatser för att öka de hörselskadade ungdomarnas simkunnighet och fysiska aktivitet. Det är också av stor betydelse för de hörselskadade och döva ungdomarna att det finns kompetent tvåspråkig (svenska och teckenspråk) personal på ungdomsmottagningar och barnahus.
|
|
| 10. |
- Brunnberg, Elinor, 1948-, et al.
(författare)
-
Hard-of-hearing adolescents reporting some other disability or tinnitus : a replication study including an age-related analysis
- 2009
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In two previous studies based on the survey, Life & Health Young 2005 in Örebro county 15-16 years old Hard-of-hearing (HH) students with some other disability (HHDIS) and HH with tinnitus (HHTINN) reported considerably higher scores for mental symptoms and substance use than adolescents ‘just‘ HH or hearing adolescents. In order to replicate these findings we analysed the 2007 survey and included adolescents in grade 7, 9 and 2 in secondary school concerning substance use and depression. We also used reference data from the corresponding adult survey Life & Health 2008. In grade 9 HHDIS (2.0%) and HHTINN (2.0 %) both reported strongly increased rates of risky alcohol consumption (55/51% versus 13%), daily tobacco use (57/54% versus 10%) and depression (43/43% versus 14%) than hearing or ´just´ HH adolescents. Similar but less pronounced changes were present in grade 7 and grade 2. In HHDIS increased risk drinking was found until age 35, increased daily tobacco use until age 50 and increased depression until age 65. In HHTINN only rate of depression was increased in adult life. HHDIS and HHTINN thus are important targets for preventive measures. In addition tinnitus in young people can be a marker like disability of vulnerability.
|
|
