1,908 research outputs found
Effect of tauroursodeoxycholic and ursodeoxycholic acid on ethanol-induced cell injuries in the human Hep G2 cell line
No full textTaurodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA) exert a protective effect in chronic cholestasis. This study reports the effect of TUDCA and UDCA on an in vitro model for ethanol-induced liver damage.
METHODS:
Hep G2 cells were incubated for 24 hours with 80 mmol/L ethanol in the presence or absence of 50 mumol/L TUDCA or UDCA. Cells were also pretreated with 80 mmol/L EtOH and then exposed to 50 mumol/L bile acids. Cytotoxicity was assessed by the metabolism of formazan (3-(4,5-dimethyl-thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide and sodium 3,3'-(phenylamino) carbonyl-3,4-tetrazolium-bis (4-methoxy-6-nitro) benzene sulfonic acid hydrase and by the release into the culture medium of different enzymes (aspartate aminotransferase, glutamate dehydrogenase, gamma-glutamyl transferase, and lactate dehydrogenase).
RESULTS:
The incubation of Hep G2 with EtOH significantly (P < 0.001) increased cytotoxicity. Both TUDCA or UDCA reduced cytoxicity to a similar extent (P < 0.001). Cells pretreated with EtOH and then added with TUDCA or UDCA responded differently because TUDCA was significantly more effective (P < 0.05) than an equimolar dose of UDCA in reversing the damage. Electron microscopic examination revealed that TUDCA and UDCA were both able to prevent mitochondrial damage and to reduce steatosis induced by EtOH.
CONCLUSIONS:
Low doses of TUDCA and UDCA protect Hep G2 cells from EtOH-induced cytotoxicity. However, TUDCA seems to be more effective than UDCA in reversing the damage
Ethanol-induced apoptosis in vitro
No full textOBJECTIVES:
The aim is to study the apoptotic process in a human hepatocyte model for ethanol (EtOH)-induced apoptosis.
DESIGN AND METHODS:
Normal human primary hepatocytes (HPH) and Hep G2 cells were exposed to increasing EtOH. 6000 cells/ sample were analyzed by transmission electron microscopy.
RESULTS:
Apoptotic cells were observed (mmol/L EtOH): 40: 6 +/-0.5%, 60:13 +/- 2% (p < 0.05), 80: 26 +/- 1% (p < 0.001) (vs. control). Two consecutive doses of 80 mmol/L for 24 h each additionally increased apoptosis 55 +/- 3% (p < 0.0001 vs. control and p < 0.001 vs. single dose). In response to this exposure, there is a stronger apoptotic activity in HPH when compared to Hep G2 (p < 0.05).
CONCLUSIONS:
In vitro, EtOH-induced apoptosis is regulated by dose level and the frequency of exposure
Wall shear stress and low density lipoprotein concentration in stented arteries
No full textThis paper was presented at the 3rd Micro and Nano Flows Conference (MNF2011), which was held at the Makedonia Palace Hotel, Thessaloniki in Greece. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, Aristotle University of Thessaloniki, University of Thessaly, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute.Current computational analysis results quantify Wall Shear Stress (WSS) and its impact on Low Density Lipoprotein (LDL) concentration of a fully deployed straight artery stent. Atherosclerosis shows
predilection in arterial regions with hemodynamic particularities, as local disturbances of WSS in space, and locally high concentrations of lipoprotein. The WSS and subsequently the LDL distribution are important indicators of stent performance. A typical 6.0 mm diameter straight stented artery is used to elucidate the WSS and the LDL transport under steady flow conditions treating the blood as a non-Newtonian fluid. Struts are 50.0 % embedded into the arterial wall. Emphasis is placed in the LDL distribution at the upstream and downstream flow regions of each strut intersection. Reduced WSS values are observed towards outlet. At the strut intersections, high WSS values are observed possibly causing platelet activation. Prone to plaque development are flow regions located at specific strut intersections (mostly at the vicinity of the curved struts) where increased LDL concentration is observed. The maximum LDL concentration over the stented artery reaches a value of 3.8 % higher than that at the entrance. The concentration at distal to any strut region was higher than proximal to the strut
Efficacy of Off-Label Topical Treatments for the Management of Androgenetic Alopecia: A Review.
No full textAndrogenetic alopecia (AGA) is characterized by non-scarring follicle miniaturization. Despite the success of approved therapies, commonly reported side effects and the need for continual use has led to the investigation of alternative therapies. The aim of this paper is to critically review the success of off-label, topical monotherapies for treatment of AGA in men. A literature search was conducted to obtain randomized, controlled and blinded studies that investigated off-label, topical, monotherapies in male patients. Hair density, hair diameter and hair growth were used to evaluate treatment success. Fourteen off-label topical therapies were investigated among the 16 studies that met inclusion criteria. Nine off-label therapies were reported to produce a significantly greater improvement in hair restoration parameters (e.g. mean change from hair count and hair diameter) as compared to placebo (p < 0.05 for all treatments). In two studies, procyanidin oligomers exhibited greater efficacy over vehicle with response to mean change in hair density (hairs/cm2) (ps < 0.0001 at Week 24). In conclusion, prostaglandin analogs and polyphenols, such as latanoprost and procyanidin oligomers, can improve hair restoration parameters in male AGA patients, possibly through targeting mechanisms proposed in the etiology of AGA. The current evidence suggests short-term (24 weeks) use may provide benefit for hair loss patients; however, long-term efficacy and safety data are required
A Practical Guide to Curing Onychomycosis: How to Maximize Cure at the Patient, Organism, Treatment, and Environmental Level
No full textOnychomycosis is a fungal nail infection caused by dermatophytes, non-dermatophyte molds, and yeasts. Treatment of this infection can be difficult, with relapse likely to occur within 2.5 years of cure. The objective of this article is to review factors that can impact cure and to suggest practical techniques that physicians can use to maximize cure rates. Co-morbidities, as well as disease severity and duration, are among the many patient factors that could influence the efficacy of antifungal therapies. Furthermore, organism, treatment, and environmental factors that may hinder cure include point mutations, biofilms, affinity for non-target enzymes, and exposure to fungal reservoirs. To address patient-related factors, physicians are encouraged to conduct confirmatory testing and treat co-morbidities such as tinea pedis early and completely. To combat organism-focused factors, it is recommended that disruption of biofilms is considered, and drugs with multiple routes of delivery and unique mechanisms of action are prescribed when traditional agents are not effective. Extending follow-up periods, using combination treatments, and considering pulse regimens may also be of benefit. Through these practical techniques, physicians can maximize cure and limit the risk of relapse and re-infection
Tinea capitis in children: a systematic review of management.
No full textAbstract BACKGROUND: Tinea capitis is the most common cutaneous fungal infection in children. OBJECTIVES: This review aims to evaluate the differences that exist between medications for the treatment of tinea capitis, to determine whether there are any significant adverse effects associated and to define the usefulness of sample collection methods. METHODS: We conducted a systematic literature search of available papers using the databases PubMed, OVID, Cochrane Libraries and ClinicalTrials.gov. Twenty-one RCTs and 17 CTs were found. RESULTS: Among the different antifungal therapies (oral and combination thereof), continuous itraconazole and terbinafine had the highest mycological cure rates (79% and 81%, respectively), griseofulvin and terbinafine had the highest clinical cure rates (46% and 58%, respectively) and griseofulvin and terbinafine had the highest complete cure rate (72% and 92%, respectively). Griseofulvin more effectively treated Microsporum infections; terbinafine and itraconazole more effectively cured Trichophyton infections. Only 1.0% of children had to discontinue medication based on adverse events. T. tonsurans was the most common organism found in North America, and hairbrush collection method is the most efficient method of sample collection. Additionally, using a hairbrush, toothbrush or cotton swab to identify the infecting organism(s) is the least invasive and most efficient method of tinea capitis sample collection in children. CONCLUSIONS: Current dosing regimens of reported drugs are effective and safe for use in tinea capitis in children
Monotherapy for Alopecia Areata: A Systematic Review and Network Meta-Analysis.
No full textBACKGROUND: There are many treatments available for alopecia areata; however, none are approved by the US Food and Drug Administration. Thus, there is clinician benefit in efficacy comparison. METHODS: A network meta-analysis was used to create direct and indirect comparisons of alopecia areata studies in addition to an inconsistency analysis, risk of bias, and quality of evidence assessment. RESULTS: For mild disease, intralesional corticosteroids were ranked the most likely to produce a response at 78.9% according to SUCRA (surface under the cumulative ranking curve) followed by topical corticosteroids (67.9%), prostaglandin analogs (67.1%), diphenylcyclopropenone (DPCP, 63.4%), topical minoxidil (61.2%), and squaric acid dibutylester (SADBE, 35.0%). In contrast, for moderate to severe disease (>50% scalp hair loss), DPCP was the top-ranked treatment (87.9%), followed by laser (77.9%), topical minoxidil (55.5%), topical corticosteroids (50.1%), SADBE (49.7%), and topical tofacitinib (47.6%). There were insufficient eligible trials to include oral tofacitinib in the network. CONCLUSION: Statistically significant evidence is presented for the use of intralesional and topical corticosteroids for treatment of mild disease and DPCP, laser, SADBE, topical minoxidil and topical corticosteroids for moderate to severe disease. Further controlled trials are required to analyze the relative efficacy of oral tofacitinib
Modulation of liver-specific cellular response to ethanol in vitro in Hep G2 cells.
No full textThe aim of this study was to investigate in vitro in a human hepatoblastoma cell line, Hep G2, the effect of ethanol (EtOH) toxicity. The ultrastructural changes were assessed by performing quantitative light and transmission electron microscopy. The second objective of this study was to define further EtOH-induced biochemical changes associated with mitochondrial function. In comparison with controls, after exposure to 80 mm EtOH cells showed: a threefold increase in length of mitochondria; proliferation, vesiculation and dilatation of smooth endoplasmic reticulum, and twofold increases in the size of lipid droplets and in their number/cell. Exposure of cells to two doses of EtOH augmented the ultrastructural alterations observed after a single dose. Cytoviability, assessed by metabolism of methylxanthine dye decreased significantly by (P < 0.0001) to 68% of the control after one dose and was further reduced after the second dose of EtOH (P < 0.001). Succinate dehydrogenase activity in cells treated for 24 hr with 80 mm EtOH was decreased to about 80% of control values after one 24-hr treatment with 80 mM EtOH and to about 55% of control values after two 24-hr exposures. This in vitro model of ethanol-induced cytotoxicity in Hep G2 cells is able to reproduce essential ultrastructural features of alcohol-related hepatitis, in humans, including steatosis and dose-dependent hepatocytotoxicity. The present work represents the first morphometric study to measure changes produced by EtOH exposure in human-derived liver cells
A narrative-based collaborative writing tool for coherent technical documents
No full textOne important feature of an effective document that makes it easy to read and understand is known as coherence. Technical documents produced collaboratively are often incoherent due to a lack of group consensus and misaligned contributions by the individual authors. However, current document planning techniques and writing tools do not provide explicit support for improving coherence. The goal of this research, therefore, is to develop and evaluate a new technique and tool that helps teams of authors to structure coherent technical documents. The coherence of a document can be attributed to the story (or narrative) it conveys to the reader. If this story is consistent and coherent, the same can be said about the document. A discourse theory such as Rhetorical Structure Theory (RST) that has been developed by linguists helps further to analyse and improve a narrative. RST explains the coherence of a text by virtue of relationships (such as “paragraph A justifies paragraph B”) between parts of the text. This research has combined the ideas from these parallel strands of research to develop a new document planning technique called narrative-based writing. The method involves writing down an explicit précis of the story (called a document narrative or DN) and then analysing it using RST. The DN and RST analysis are then used to structure the eventual document. To extend the usability of narrative-based writing to geographically-dispersed authors, I have designed and implemented a collaborative tool that allows co-authors to edit, analyse and review DNs. The thorough design for the tool uses a combination of three models (conceptual, business process and functional) culminating in a set of functions that enable collaborative narrative-based writing. This dissertation discusses how, in the future, these functions could be incorporated in existing collaborative writing tools. Implementing this tool, albeit in its current prototypic state, has been invaluable in understanding the complexities of modelling and manipulating DNs and RST structures. Initial investigations using the new technique and tool have been positive, encouraging me to continue the research and evaluation in this field
Evaluatie suppleties Noord-Holland en Texel
No full textNote: NH-93.ANV002a.pdf bevat het hoofdrapport en NH-93.ANV002b.pdf bevat alle bijlagen. ----- De minister van Verkeer en Waterstaat heeft de kamer een interim-nota kustverdediging in 1993 toegezegd, waarin het kustverdedigingsbeleid wordt geëvalueerd. Een onderdeel van deze evaluatie is de evaluatie van de zandsuppleties. Om deze evaluatie uit te voeren is de werkgroep EVAZAND, onder leiding van de Dienst Getijdewateren, ingesteld. De evaluatie beperkt zich in principe tot de morfologische aspecten en is hoofdzakelijk gericht op het bepalen van de doelmatigheid of de effectiviteit van zandsuppleties. Omdat suppleties van 1990 of later zich vanwege de korte levensduur nauwelijks lenen voor evaluatie is een selectie gemaakt uit de suppleties van vóór 1990. Deze nota dient als de bijdrage van de Directie Noord-Holland aan het project EVAZAND en bevat de evaluatie van alle grote zandsuppleties van Noord-Holland en Texel van vóór 1990.EVAZAN
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