| 1. |
- Narangifard, A., et al.
(författare)
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Human skin barrier formation takes place via a cubic to lamellar lipid phase transition as analyzed by cryo-electron microscopy and EM-simulation
- 2018
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 366:2, s. 139-151
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Tidskriftsartikel (refereegranskat)abstract
- The skin's permeability barrier consists of stacked lipid sheets of splayed ceramides, cholesterol and free fatty acids, positioned intercellularly in the stratum corneum. We report here on the early stage of skin barrier formation taking place inside the tubuloreticular system in the secretory cells of the topmost viable epidermis and in the intercellular space between viable epidermis and stratum corneum. The barrier formation process was analysed in situ in its near-native state, using cryo-EM combined with molecular dynamics modeling and EM simulation. Stacks of lamellae appear towards the periphery of the tubuloreticular system and they are closely associated with granular regions. Only models based on a bicontinuous cubic phase organization proved compatible with the granular cryo-EM patterns. Only models based on a dehydrated lamellar phase organization agreed with the lamellar cryo-EM patterns. The data support that human skin barrier formation takes place via a cubic to lamellar lipid phase transition.
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| 10. |
- Abd-el-Gawa, G, et al.
(författare)
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Vitamin B12 and folate after 5-12 years of continent ileal urostomy (Kock reservoir) in children and adolescents.
- 2002
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Ingår i: European urology. - : Elsevier BV. - 0302-2838. ; 41:2, s. 199-205
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Tidskriftsartikel (refereegranskat)abstract
- To assess B12 and folate deficiency after continent urinary diversion via a Kock continent urinary reservoir in children and adolescents.Ten boys and 10 girls (10.8-18 years old at surgery) were operated with a Kock reservoir and followed for 5-12 years (mean 8.5). The follow-up period was divided into early (3 months-5 years, EFU) and late (5-12 years, LFU) follow-up. Patients were investigated for haemoglobin, serum iron, total iron binding capacity (TIBC), serum Vitamin B12, serum and blood folate, methylmalonic acid (MMA), homocystine and glomerular filtration rate.Two patients developed subnormal B12 values (median 107.5 pmol/l), one at the EFU, and the other at LFW. The B12 value decreased during the LFU compared to the EFU in nine patients, but it was still within the normal range. Two patients with renal impairment had elevated MMA with normal B12 values. Five patients had high values of homocystine with folate deficiency and/or B12 deficiency and renal impairment. Plasma folate mean value was normal during the whole follow-up. Blood folate was below normal in five patients at the EFU. Two of these five patients, in addition to three patients, had low values at the LFU. Three of four patients with remaining short terminal ileum (20-45 cm) had normal B12 values at both the EFU & LFU and one had low values at the LFU. Six patients had subnormal GFR at the LFU.To a similar degree as in adults, Vitamin B12, folate and iron deficiency can occur in children and adolescents after continent urinary diversion using an ileal segment. Therefore, Vitamin B12 and folate should be monitored regularly in these patients. Serum MMA and homocystine may offer increased detection of Vitamin B12 deficiency, especially in the patients with normal renal function. Vitamin B12 deficiency is neither correlated with the time elapsed since surgery, nor with the ileum length. Patients are usually asymptomatic, so patients with true B12 deficiency should be identified and placed on life-long Vitamin B12 therapy. An adequate synthetic folic acid as supplements or fortified food is recommended for patients with folate deficiency.
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| 11. |
- Abd-El-Gawad, G, et al.
(författare)
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Early and late metabolic alterations in children and adolescents with a kock urinary reservoir.
- 1999
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Ingår i: BJU international. - : Wiley. - 1464-4096 .- 1464-410X. ; 83:3, s. 285-9
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Tidskriftsartikel (refereegranskat)abstract
- To assess the early and late metabolic effects of urinary diversion in children and adolescents with a Kock urinary reservoir.Thirteen children (aged 10.8- 16 years) and seven adolescents (aged 16-18 years; 10 girls and 10 boys), underwent surgery for congenital urinary incontinence. They were followed for 3-10 years (mean 6.5), divided into an early (3 months to 2 years) and a late (2-10 years) period, and assessed for renal function and any metabolic effects.At the early and late follow-up, one of 19 and three of 16 patients, respectively, had metabolic acidosis. Hyperchloraemia was present in four of 20 patients at the early and in eight of 18 at the late follow-up. Serum creatinine was increased in four of 20 patients at the early and eight of 18 at the late follow-up. In patients with infrequent reservoir emptying (
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| 12. |
- Abd-el-Gawad, G, et al.
(författare)
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Evaluation of Kock urinary reservoir function in children and adolescents at 3-10 years' follow-up.
- 1999
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Ingår i: Scandinavian journal of urology and nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 33:3, s. 149-55
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate Kock reservoir function in children and adolescents operated for congenital urinary incontinence and to determine the complication rate. Reservoir function was investigated in 13 children (age range 10.8-16 years) and 7 adolescents (age range 16-18 years) through enterocystometry, enterocystoscopy and patient history. Patients were followed up for 3-10 years. The follow-up was reported as early (3 months-2 years) and late (2-10 years) postoperative periods. At early follow-up reservoir capacity was high in four patients and normal in the remaining patients. A low reservoir pressure was accompanied by high capacity and compliance. On enterocystometry first sensation for emptying was experienced in 82% of patients at early follow-up and 92% at late follow-up. Reservoir contractions were recorded in 60% of patients at early follow-up and 65% at late follow-up. The contractions were recorded at an average reservoir capacity of 270 ml at early follow-up and 340 ml at late follow-up. The complication rate was high in the child group compared with that in adolescents. Of 13 patients with at least one reservoir complication 10 were from the child group. Nipple dysfunction (angled nipple, prolapsed or stenosed stoma) occurred in 35% of patients, stones in 40% and bleeding during catheterization in 15%. Revision was performed in 38% of the child group and 15% of the adolescents. Reservoir perforation was observed in two patients at 6 and 9 years postoperatively. At late follow-up continence was excellent in 17 of 19 patients and good in 2. We conclude that the Kock reservoir is a good modality for urinary diversion, but the complication incidence is high in the child group (<16 years). Stability of the reservoir in terms of volume and low internal pressures was achieved one year after operation, except in the patients with infrequent reservoir emptying. A time-related increase in the reservoir sensitivity and contractility was reported on enterocystometry. Nipple dysfunction is common during the first two years after surgery, particularly in the child group. Stones may form 3-4 years after surgery. Satisfactory continence was achieved in all patients, although a revisional operation was necessary in some patients in order to obtain permanent continence.
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| 13. |
- Abd-el-Gawad, G, et al.
(författare)
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Kock urinary reservoir maturation in children and adolescents: consequences for kidney and upper urinary tract.
- 1999
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Ingår i: European urology. - : Elsevier BV. - 0302-2838 .- 1421-993X. ; 36:5, s. 443-9
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Tidskriftsartikel (refereegranskat)abstract
- To study Kock reservoir maturation in children and adolescents and its effects on the kidneys and upper urinary tract.Ten boys and 10 girls, aged 10.8-18 years, had Kock reservoir surgery for congenital urinary incontinence. They were followed for 3-10 years, divided into 3 different periods, and assessed with urography and enterocystography, the findings of which were correlated to renal function as measured by (51)Cr EDTA clearance, reservoir endoscopy and patient's history.The reservoir was located in the pelvis and remained in this position throughout the whole follow-up in 75% of patients and in the lower or midabdomen in 25%. Angled efferent nipple seen on enterocystoscopy or enterocystography coincided with nipple dysfunction, reservoir malposition or infrequent reservoir emptying. Upper urinary tract dilatation was detected in 84% of patients 3 months after surgery, 25% at 1 year and 30% at 2-10 years. The dilatation was improved in 56% of patients and unchanged in 25% after 1 year. The situation continued to improve at late follow-up. New focal renal scars were radiologically detected in 1 of 19 at early and in another 1 of 17 patients at late follow-up. Progression of old scars was detected in 1 of 19 at early and in 4 of 17 at late follow-up. Eight of 19 cases had deterioration of renal function with a change in the split renal function. Of these 8 patients, 7 reported infrequent reservoir evacuation.Kock reservoir is a useful form of urinary diversion in children and adolescents with congenital urinary incontinence. Radiological examinations are good methods of follow-up of the maturation of the pouch and its effects on the urinary tract and for detection of complications. Urinary tract dilatation is a frequent finding early after surgery but it subsides in most cases 3-12 months after surgery. Long-term efferent nipple dysfunction may be the result of angulation, reservoir stones, malposition and/or overdistension. Permanent renal damage may be due to pyelonephritis, stones, infrequent reservoir emptying or urinary obstruction. A strict regime of reservoir evacuation to avoid overdistension and nipple dysfunction and to decrease the possibility of renal function deterioration is strongly advisable in these patients. It is imperative that their own management of the reservoir is continuously supervised.
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| 14. |
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| 15. |
- Bill-Axelson, Anna, et al.
(författare)
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Radical prostatectomy versus watchful waiting in localized prostate cancer : the Scandinavian prostate cancer group-4 randomized trial
- 2008
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 100:16, s. 1144-1154
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one randomized trial. In 2005, we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up. We now report results after 3 more years of follow-up.METHODS: From October 1, 1989, through February 28, 1999, 695 men with clinically localized prostate cancer were randomly assigned to radical prostatectomy (n = 347) or watchful waiting (n = 348). Follow-up was complete through December 31, 2006, with histopathologic review and blinded evaluation of causes of death. Relative risks (RRs) were estimated using the Cox proportional hazards model. Statistical tests were two-sided.RESULTS: During a median of 10.8 years of follow-up (range = 3 weeks to 17.2 years), 137 men in the surgery group and 156 in the watchful waiting group died (P = .09). For 47 of the 347 men (13.5%) who were randomly assigned to surgery and 68 of the 348 men (19.5%) who were not, death was due to prostate cancer. The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up. At 12 years, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer (difference = 5.4%, 95% confidence interval [CI] = 0.2 to 11.1%), for a relative risk of 0.65 (95% CI = 0.45 to 0.94; P = .03). The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up. At 12 years, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases (difference = 6.7%, 95% CI = 0.2 to 13.2%), for a relative risk of 0.65 (95% CI = 0.47 to 0.88; P = .006). Among men who underwent radical prostatectomy, those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it (RR = 14.2, 95% CI = 3.3 to 61.8; P < .001).CONCLUSION: Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery.
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| 18. |
- Colldén, Hannah, et al.
(författare)
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Comprehensive Sex Steroid Profiling in Multiple Tissues Reveals Novel Insights in Sex Steroid Distribution in Male Mice
- 2022
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 163:3
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Tidskriftsartikel (refereegranskat)abstract
- A comprehensive atlas of sex steroid distribution in multiple tissues is currently lacking, and how circulating and tissue sex steroid levels correlate remains unknown. Here, we adapted and validated a gas chromatography tandem mass spectrometry method for simultaneous measurement of testosterone (T), dihydrotestosterone (DHT), androstenedione, progesterone (Prog), estradiol, and estrone in mouse tissues. We then mapped the sex steroid pattern in 10 different endocrine, reproductive, and major body compartment tissues and serum of gonadal intact and orchiectomized (ORX) male mice. In gonadal intact males, high levels of DHT were observed in reproductive tissues, but also in white adipose tissue (WAT). A major part of the total body reservoir of androgens (T and DHT) and Prog was found in WAT. Serum levels of androgens and Prog were strongly correlated with corresponding levels in the brain while only modestly correlated with corresponding levels in WAT. After orchiectomy, the levels of the active androgens T and DHT decreased markedly while Prog levels in male reproductive tissues increased slightly. In ORX mice, Prog was by far the most abundant sex steroid, and, again, WAT constituted the major reservoir of Prog in the body. In conclusion, we present a comprehensive atlas of tissue and serum concentrations of sex hormones in male mice, revealing novel insights in sex steroid distribution. Brain sex steroid levels are well reflected by serum levels and WAT constitutes a large reservoir of sex steroids in male mice. In addition, Prog is the most abundant sex hormone in ORX mice.
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| 19. |
- Colldén, Hannah, et al.
(författare)
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Dehydroepiandrosterone Supplementation Results in Varying Tissue-specific Levels of Dihydrotestosterone in Male Mice
- 2022
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 163:12
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Tidskriftsartikel (refereegranskat)abstract
- Dehydroepiandrosterone (DHEA), an adrenal androgen precursor, can be metabolized in target tissues into active sex steroids. It has been proposed that DHEA supplementation might result in restoration of physiological local sex steroid levels, but knowledge on the effect of DHEA treatment on local sex steroid levels in multiple tissues is lacking. To determine the effects of DHEA on tissue-specific levels of sex steroids, we treated orchiectomized (ORX) male mice with DHEA for 3 weeks and compared them with vehicle-treated ORX mice and gonadal intact mice. Intra-tissue levels of sex steroids were analyzed in reproductive organs (seminal vesicles, prostate, m. levator ani), major body compartments (white adipose tissue, skeletal muscle, and brain), adrenals, liver, and serum using a sensitive and validated gas chromatography-mass spectrometry method. DHEA treatment restored levels of both testosterone (T) and dihydrotestosterone (DHT) to approximately physiological levels in male reproductive organs. In contrast, this treatment did not increase DHT levels in skeletal muscle or brain. In the liver, DHEA treatment substantially increased levels of T (at least 4-fold) and DHT (+536%, P < 0.01) compared with vehicle-treated ORX mice. In conclusion, we provide a comprehensive map of the effect of DHEA treatment on intra-tissue sex steroid levels in ORX mice with a restoration of physiological levels of androgens in male reproductive organs while DHT levels were not restored in the skeletal muscle or brain. This, and the unexpected supraphysiological androgen levels in the liver, may be a cause for concern considering the uncontrolled use of DHEA.
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| 20. |
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| 21. |
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| 23. |
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| 24. |
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| 25. |
- Haglund, U, et al.
(författare)
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Complications related to pneumoperitoneum
- 1995
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Ingår i: Complications of Laparoscopic Surgery. - : Quality Medical Publishing Inc., St. Louis, Missouri. ; , s. 26-
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
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| 26. |
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| 27. |
- Johnsen, GK, et al.
(författare)
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Sorption properties of the human stratum corneum
- 2011
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Ingår i: Skin pharmacology and physiology. - : S. Karger AG. - 1660-5535 .- 1660-5527. ; 24:4, s. 190-198
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Tidskriftsartikel (refereegranskat)abstract
- Water sorption is important for the overall structure and function of keratinized tissues such as the human epidermal stratum corneum (SC). In this study we report on a gravimetric method for studying sorption properties of human SC, both from heel and female breast skin. Changes in mass were measured as the relative humidity was altered in steps under controlled environmental conditions. The possibility of hysteresis is also discussed. Furthermore, we have found that the sorption time constants show triphasic behaviour during absorption, but not during desorption. This behaviour is connected to the 3 different types of water present in the SC. Water also enters the SC much more rapidly compared to its exit at relative humidities <50%. Finally, the amount of time between sample preparation and onset of measurement seems to have an effect on the absorption rate, but less on the total amount of water absorbed.
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| 28. |
- Lundborg, Magnus, et al.
(författare)
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Human skin barrier structure and function analyzed by cryo-EM and molecular dynamics simulation
- 2018
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Ingår i: Journal of Structural Biology. - : Academic Press. - 1047-8477 .- 1095-8657. ; 203:2, s. 149-161
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Tidskriftsartikel (refereegranskat)abstract
- In the present study we have analyzed the molecular structure and function of the human skin's permeability barrier using molecular dynamics simulation validated against cryo-electron microscopy data from near native skin. The skin's barrier capacity is located to an intercellular lipid structure embedding the cells of the superficial most layer of skin - the stratum corneum. According to the splayed bilayer model (Iwai et al., 2012) the lipid structure is organized as stacked bilayers of ceramides in a splayed chain conformation with cholesterol associated with the ceramide sphingoid moiety and free fatty acids associated with the ceramide fatty acid moiety. However, knowledge about the lipid structure's detailed molecular organization, and the roles of its different lipid constituents, remains circumstantial. Starting from a molecular dynamics model based on the splayed bilayer model, we have, by stepwise structural and compositional modifications, arrived at a thermodynamically stable molecular dynamics model expressing simulated electron microscopy patterns matching original cryo-electron microscopy patterns from skin extremely closely. Strikingly, the closer the individual molecular dynamics models' lipid composition was to that reported in human stratum corneum, the better was the match between the models' simulated electron microscopy patterns and the original cryo-electron microscopy patterns. Moreover, the closest-matching model's calculated water permeability and thermotropic behaviour were found compatible with that of human skin. The new model may facilitate more advanced physics-based skin permeability predictions of drugs and toxicants. The proposed procedure for molecular dynamics based analysis of cellular cryo-electron microscopy data might be applied to other biomolecular systems.
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| 29. |
- Lundborg, Magnus, et al.
(författare)
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Predicting drug permeability through skin using molecular dynamics simulation
- 2018
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Ingår i: Journal of Controlled Release. - : Elsevier. - 0168-3659 .- 1873-4995. ; 283, s. 269-279
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Tidskriftsartikel (refereegranskat)abstract
- Understanding and predicting permeability of compounds through skin is of interest for transdermal delivery of drugs and for toxicity predictions of chemicals. We show, using a new atomistic molecular dynamics model of the skin's barrier structure, itself validated against near-native cryo-electron microscopy data from human skin, that skin permeability to the reference compounds benzene, DMSO (dimethyl sulfoxide), ethanol, codeine, naproxen, nicotine, testosterone and water can be predicted. The permeability results were validated against skin permeability data in the literature. We have investigated the relation between skin barrier molecular organization and permeability using atomistic molecular dynamics simulation. Furthermore, it is shown that the calculated mechanism of action differs between the five skin penetration enhancers Azone, DMSO, oleic acid, stearic acid and water. The permeability enhancing effect of a given penetration enhancer depends on the permeating compound and on the concentration of penetration enhancer inside the skin's barrier structure. The presented method may open the door for computer based screening of the permeation of drugs and toxic compounds through skin.
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| 30. |
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| 31. |
- Meuller, Bengt, et al.
(författare)
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Review of Spark Discharge Generators for Production of Nanoparticle Aerosols
- 2012
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Ingår i: Aerosol Science and Technology. - : Informa UK Limited. - 1521-7388 .- 0278-6826. ; 46:11, s. 1256-1270
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Forskningsöversikt (refereegranskat)abstract
- In the growing field of nanotechnology there is an increasing need to develop production methods for nanoparticles, especially methods that provide control and reproducibility. The spark discharge generator (SDG) is a versatile device for the production of nanoparticle aerosols. It can produce aerosol nanoparticles in the entire nanometer range (1-100 nm), and beyond. Depending on requirements, and the system used, these nanoparticles can be completely contamination free and composed of one or more materials. This provides a unique opportunity to create new materials on the nanoscale. Already in use in semiconductor, materials, health and environmental research, the SDG shows promise for yet more applications. If needed, particle production by the SDG could be scaled up using parallel generators facilitating continuous high-volume production of aerosol nanoparticles. Still, there is a surprisingly low knowledge of fundamental processes in the SDG. In this article we present a thorough review of the most common and relevant SDGs and the theory of their operation. Some possible improvements are also discussed.
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| 32. |
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| 33. |
- Narangifard, Ali, et al.
(författare)
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Molecular Reorganization during the Formation of the Human Skin Barrier Studied In Situ
- 2021
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 141:5, s. 1243-1253
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Tidskriftsartikel (refereegranskat)abstract
- In vertebrates, skin upholds homeostasis by preventing body water loss. The skin's permeability barrier is located intercellularly in the stratum corneum and consists of stacked lipid lamellae composed of ceramides, cholesterol, and free fatty acids. We have combined cryo-electron microscopy with molecular dynamics modeling and electron microscopy simulation in our analysis of the lamellae's formation, a maturation process beginning in stratum granulosum and ending in stratum corneum. Previously, we have revealed the lipid lamellae's initial- and end-stage molecular organizations. In this study, we reveal two cryo-electron microscopy patterns representing intermediate stages in the lamellae's maturation process: a single-band pattern with 2.0-2.5 nm periodicity and a two-band pattern with 5.5-6.0 nm periodicity, which may be derived from lamellar lipid structures with 4.0-5.0 nm and 5.5-6.0 nm periodicity, respectively. On the basis of the analysis of the data now available on the four maturation stages identified, we can present a tentative molecular model for the complete skin barrier formation process.
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| 34. |
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| 35. |
- Nicander, I, et al.
(författare)
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Lipid content and electrical impedance
- 1998
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Ingår i: Current problems in dermatology. - Basel : KARGER. - 1421-5721. ; 26, s. 165-176
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Tidskriftsartikel (refereegranskat)
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| 36. |
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| 37. |
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| 38. |
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| 39. |
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| 40. |
- Norlen, L
(författare)
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Current understanding of skin barrier morphology
- 2013
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Ingår i: Skin pharmacology and physiology. - : S. Karger AG. - 1660-5535 .- 1660-5527. ; 26:4-6, s. 213-216
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Tidskriftsartikel (refereegranskat)abstract
- It was recently shown that the stratum corneum fat layer, i.e. the skin permeability barrier, has a unique molecular arrangement - stacked bilayers of fully extended ceramides with cholesterol molecules associated with the ceramide sphingoid moiety. We here give a brief historical perspective to the field of skin permeability barrier research and specifically address some selected contributions to the current understanding of skin barrier morphology.
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| 41. |
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| 42. |
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| 43. |
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| 44. |
- Norlen, L
(författare)
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Is Oil a Balsam for Baby Skin?
- 2016
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Ingår i: Acta dermato-venereologica. - : Medical Journals Sweden AB. - 1651-2057 .- 0001-5555. ; 96:3, s. 291-291
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Tidskriftsartikel (refereegranskat)
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| 45. |
- Norlén, L., et al.
(författare)
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Molecular cryo-electron tomography of vitreous tissue sections : current challenges
- 2009
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Ingår i: Journal of Microscopy. - : Wiley. - 0022-2720 .- 1365-2818. ; 235:3, s. 293-307
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Tidskriftsartikel (refereegranskat)abstract
- Electron tomography of vitreous tissue sections (tissue TOVIS) allows the study of the three-dimensional structure of molecular complexes in a near-native cellular context. Its usage is, however, limited by an unfortunate combination of noisy and incomplete data, by a technically demanding sample preparation procedure, and by a disposition for specimen degradation during data collection. Here we outline some major challenges as experienced from the application of TOVIS to human skin. We further consider a number of practical measures as well as theoretical approaches for its future development.
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| 46. |
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| 47. |
- Norlen, L
(författare)
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Molecular skin barrier models and some central problems for the understanding of skin barrier structure and function
- 2003
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Ingår i: Skin pharmacology and applied skin physiology. - : S. Karger AG. - 1422-2868. ; 16:4, s. 203-211
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Tidskriftsartikel (refereegranskat)abstract
- A better understanding of the structure and function of the human skin barrier is a prerequisite for a more rational design of transdermal drug administration systems. The study of biological structural organisation is, however, confronted with many difficulties, and interpretations of skin barrier-related data should therefore be done with caution. The recently developed ‘single gel-phase model’ constitutes an attempt to interpret structural and functional skin barrier data from a biophysical standpoint.
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| 48. |
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| 49. |
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| 50. |
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