Vitamin D Derivative

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William R Cantrell - One of the best experts on this subject based on the ideXlab platform.

Alexander Marsland Bsc Mrcp - One of the best experts on this subject based on the ideXlab platform.

  • interventions for chronic palmoplantar pustulosis
    Cochrane Database of Systematic Reviews, 2015
    Co-Authors: Robert J G Chalmers, Sally Hollis, Jo Leonardibee, Christopher E M Griffiths, Alexander Marsland Bsc Mrcp
    Abstract:

    BackgrounD Palmoplantar pustulosis is a chronic inflammatory Disease in which sterile, relapsing pustules appear on the palms anD soles, possibly in conjunction with other symptoms. The previous Cochrane Review on this topic was publisheD in 2006, before biological treatments were extensively useD. Objectives To assess the effects of interventions for chronic palmoplantar pustulosis to inDuce anD maintain complete remission. Search methoDs We searcheD the following Databases up to March 2019: Cochrane Skin SpecialiseD Register, CENTRAL, MEDLINE, Embase, anD LILACS. We also searcheD five trials registers anD checkeD the reference lists of the incluDeD stuDies for further references to relevant ranDomiseD controlleD trials (RCTs). Selection criteria We consiDereD RCTs incluDing people with palmoplantar pustulosis or chronic palmoplantar pustular psoriasis assessing topical therapy, systemic therapy, combinations of topical or systemic therapies, or non-pharmacological therapies compareD with placebo, no intervention, or each other. Data collection anD analysis We useD stanDarD methoDological proceDures expecteD by Cochrane. Our outcomes incluDeD 'Proportion of participants cleareD or almost cleareD', 'Proportion of participants with aDverse effects serious or severe enough to cause withDrawal', 'Proportion of participants with at least 50% improvement in Disease severity', anD 'Proportion of participants with aDverse effects'. Main results We incluDeD 37 stuDies (1663 participants; mean age 50 years (range 34 to 63); 24% males). These stuDies reporteD conDition severity Differently. ArounD half of the incluDeD trials stateD the setting (hospitals, community clinics, or both). More than half of the stuDies were at high risk of bias in at least one Domain. Our incluDeD stuDies assesseD mainly systemic treatments (retinoiDs, ciclosporin, biologics, etretinate + PUVA (combination of psoralens anD long-wave ultraviolet raDiation) therapy combineD, anD antibiotics), but also topical treatments (DermocorticoiDs, Vitamin D) anD phototherapy (PUVA, ultraviolet A1 (UVA1)). Other interventions were assesseD by single stuDies. The most common comparator was placebo. All results presenteD in this abstract were assesseD in the short term (mean treatment Duration was 11 weeks (range 8 to 24 weeks)) anD are baseD on participants with chronic palmoplantar pustulosis. All outcome time point measurements were taken from baseline anD assesseD at the enD of treatment. Short-term anD long-term outcomes were DefineD as measurement up to 24 weeks after ranDomisation anD between 24 anD 104 weeks after ranDomisation, respectively. One trial (188 participants) assesseD the topical Vitamin D Derivative maxacalcitol versus placebo anD founD that maxacalcitol may be more effective than placebo in achieving clearance (risk ratio (RR) 7.83, 95% confiDence interval (CI) 1.85 to 33.12; low-quality eviDence), anD the risk of aDverse effects (such as milD local irritation, pruritus, anD haematological or urinary test abnormalities) is probably similar in both groups (RR 0.87, 95% CI 0.64 to 1.19; moDerate-quality eviDence). Severity was not reporteD. Two trials (49 participants) assesseD PUVA therapy versus placebo or no treatment, proviDing very low-quality eviDence. ADverse effects were reporteD with oral PUVA (incluDing nausea, ankle swelling, anD non-purulent conjunctivitis) anD with local PUVA (incluDing blistering, erythema, anD pruritus). With regarD to the systemic retinoiD alitretinoin, one trial (33 participants; moDerate-quality eviDence) showeD that alitretinoin probably makes little or no Difference in reDucing severity when compareD to placebo (RR 0.69, 95% CI 0.36 to 1.30). A similar number of aDverse events were reporteD in both treatment groups, incluDing heaDache, cheilitis, nausea, arthralgia, anD nasopharyngitis (RR 0.84, 95% CI 0.61 to 1.17). Clearance was not reporteD. There may be little or no Difference between etanercept anD placebo in achieving clearance (RR 1.64, 95% CI 0.08 to 34.28; 1 stuDy; 15 participants; low-quality eviDence); however, the 95% CI was very wiDe, showing there may be a Difference between groups. Severity was not measureD. More patients treateD with placebo may achieve reDuceD severity than those treateD with ustekinumab, but the wiDe 95% CI inDicates there might be little or no Difference between groups anD there might be greater effect with ustekinumab (RR 0.48, 95% CI 0.11 to 2.13; 1 stuDy; 33 participants; low-quality eviDence). Clearance was not reporteD. It is uncertain whether guselkumab increases clearance when compareD to placebo (2 stuDies; 154 participants) because the quality of eviDence is very low, but guselkumab probably better reDuces Disease severity (RR 2.88, 95% CI 1.24 to 6.69; 1 stuDy; 49 participants; moDerate-quality eviDence). Secukinumab is probably superior to placebo in reDucing severity (RR 1.55, 95% CI 1.02 to 2.35; 1 stuDy; 157 participants; moDerate-quality eviDence), but our clearance outcome was not reporteD. None of these trials reporteD on occurrence of aDverse effects. Only two of the stuDies DiscusseD above reporteD aDverse effects serious or severe enough to cause withDrawal. Guselkumab may cause more serious aDverse events when compareD to placebo, but there is uncertainty Due to the very wiDe 95% CI showing there may be little or no Difference anD showing more events with placebo (RR 2.88, 95% CI 0.32 to 25.80; 1 stuDy; 49 participants; low-quality eviDence). Secukinumab probably causes more serious aDverse events than placebo (RR 3.29, 95% CI 1.40 to 7.75; 1 stuDy; 157 participants; moDerate-quality eviDence). Authors' conclusions EviDence is lacking for major chronic palmoplantar pustulosis treatments such as superpotent corticosteroiDs, phototherapy, acitretin, methotrexate, anD ciclosporin. Risk of bias anD imprecision limit our confiDence. Maxacalcitol may be more effective than placebo in achieving clearance in the short term (low-quality eviDence), anD the risk of aDverse effects is probably similar (moDerate-quality eviDence). Oral alitretinoin is probably no more effective than placebo in reDucing severity, with a similar risk of aDverse effects (moDerate-quality eviDence). RegarDing biological treatments, we are uncertain of the effect of etanercept on clearance anD the effect of ustekinumab on severity (low-quality eviDence). Secukinumab anD guselkumab are probably superior to placebo in reDucing severity (moDerate-quality eviDence). ADverse events not requiring withDrawal were not reporteD for these treatments. Reporting of serious aDverse effects was incomplete: compareD to placebo, secukinumab probably causeD more participant withDrawals (moDerate-quality eviDence), but we are uncertain of the effect of guselkumab (low-quality eviDence). Future trials shoulD assess commonly useD treatments using valiDateD severity anD quality of life scales.

E Sbidian - One of the best experts on this subject based on the ideXlab platform.

  • interventions for chronic palmoplantar pustulosis abriDgeD cochrane systematic review anD graDe assessments
    British Journal of Dermatology, 2020
    Co-Authors: Grace Obeid, Lisa Kirby, Carolyn Hughes, E Sbidian, Le L Cleach
    Abstract:

    BackgrounD Palmoplantar pustulosis (PPP) is a chronic inflammatory Disease in which sterile anD relapsing pustules appear on the palms anD soles. Objectives To assess the effects of interventions for chronic PPP to inDuce anD maintain complete remission. MethoDs We searcheD for ranDomiseD controlleD trials (RCTs), incluDing people with PPP or chronic palmoplantar pustular psoriasis, in Cochrane Skin SpecialiseD Register, CENTRAL, MEDLINE, Embase, LILACS anD eight trials registers up to July 2020. StuDy selection, Data extraction anD risk of bias assessment were carrieD out inDepenDently by two review authors. Certainity of eviDence was assesseD using the GRADE (GraDing of RecommenDations Assessment, Development anD Evaluation) methoD. Results We incluDeD 37 RCTs (1663 participants, 76% women, mean age 50 years).. Mean treatment Duration was 11 weeks. Topical Vitamin D Derivative may be more effective than placebo in achieving clearance [risk ratio (RR) 7.83, 95% confiDence interval (CI) 1.85 to 33.12; low-certainity eviDence from 2 trials].. Concerning biologic therapies, there was little or no Difference between etanercept anD placebo in achieving clearance (low-certainity eviDence from one trial), ustekinumab is less effective than placebo in reDucing severity (low-certainty eviDence from one trial), guselkumab anD secukinumab probably better reDuce Disease severity (RR 2.88, 95% CI 1.24 to 6.69 anD 1.55, 95% CI 1.02 to 2.35 respectively, moDerate-certainty eviDence from 2 anD one trial respectively) but may cause more serious aDverse events when compareD to placebo. Conclusions EviDence is lacking for or against major chronic PPP treatments. Risk of bias anD imprecision limit our confiDence in the results.

  • persistence of treatment with biologics for patients with psoriasis a real worlD analysis of 16 545 biologic naive patients from the french national health insurance Database sniiram
    British Journal of Dermatology, 2019
    Co-Authors: E Sbidian, M Mezzarobba, Alain Weill, Joel Coste, Jeremie Rudant
    Abstract:

    BackgrounD Long-term clinical effectiveness of biologics in psoriasis is neeDeD. Objectives We aimeD to assess the long-term persistence of biologics useD to treat psoriasis in a real-life setting. MethoDs All aDults with psoriasis having been registereD in the French National Health Insurance Database (SNIIRAM) between 2008 anD 2016 were eligible for inclusion. Psoriasis was DefineD as the fulfilment of at least two prescriptions for topical formulations of a Vitamin D Derivative within a 2-year perioD. The stuDy population compriseD biologic-naive patients, i.e. those with a first prescription of etanercept, infliximab, aDalimumab or ustekinumab. Persistence of treatment with a biologic was DefineD as the time interval between initiation anD Discontinuation. Results In this nationwiDe population-baseD cohort, 16 545 out of 874 549 patients with psoriasis were biologic-naive (mean age 48·6 years; males 57·3%, mean follow-up 3·6 years). The mean ± SD length of follow-up for biologic-naive patients was 3·6 ± 2·4 years. There were 9988 treatment Discontinuations. Kaplan-Meier survival analyses revealeD a persistence rate of 61·9% for the first, 33·3% for the thirD anD 22·6% for the fifth year. Ustekinumab haD a higher persistence rate than the other biologics. This finDing shoulD be interpreteD with caution, in view of Differences in aDministration between the biologics. About 85% of patients, having DiscontinueD their first biologic, resumeD systemic treatment of some type in the following year (biologics in 85% of cases). Conclusions Our Data suggest that biologics are less effective than physicians have been leD to believe in a real-life, nonselecteD population. Further, long-term Disease control requires several courses of Different biologics.

Le L Cleach - One of the best experts on this subject based on the ideXlab platform.

  • interventions for chronic palmoplantar pustulosis abriDgeD cochrane systematic review anD graDe assessments
    British Journal of Dermatology, 2020
    Co-Authors: Grace Obeid, Lisa Kirby, Carolyn Hughes, E Sbidian, Le L Cleach
    Abstract:

    BackgrounD Palmoplantar pustulosis (PPP) is a chronic inflammatory Disease in which sterile anD relapsing pustules appear on the palms anD soles. Objectives To assess the effects of interventions for chronic PPP to inDuce anD maintain complete remission. MethoDs We searcheD for ranDomiseD controlleD trials (RCTs), incluDing people with PPP or chronic palmoplantar pustular psoriasis, in Cochrane Skin SpecialiseD Register, CENTRAL, MEDLINE, Embase, LILACS anD eight trials registers up to July 2020. StuDy selection, Data extraction anD risk of bias assessment were carrieD out inDepenDently by two review authors. Certainity of eviDence was assesseD using the GRADE (GraDing of RecommenDations Assessment, Development anD Evaluation) methoD. Results We incluDeD 37 RCTs (1663 participants, 76% women, mean age 50 years).. Mean treatment Duration was 11 weeks. Topical Vitamin D Derivative may be more effective than placebo in achieving clearance [risk ratio (RR) 7.83, 95% confiDence interval (CI) 1.85 to 33.12; low-certainity eviDence from 2 trials].. Concerning biologic therapies, there was little or no Difference between etanercept anD placebo in achieving clearance (low-certainity eviDence from one trial), ustekinumab is less effective than placebo in reDucing severity (low-certainty eviDence from one trial), guselkumab anD secukinumab probably better reDuce Disease severity (RR 2.88, 95% CI 1.24 to 6.69 anD 1.55, 95% CI 1.02 to 2.35 respectively, moDerate-certainty eviDence from 2 anD one trial respectively) but may cause more serious aDverse events when compareD to placebo. Conclusions EviDence is lacking for or against major chronic PPP treatments. Risk of bias anD imprecision limit our confiDence in the results.

Nanjoo Suh - One of the best experts on this subject based on the ideXlab platform.

  • gene expression profiling changes inDuceD by a novel gemini Vitamin D Derivative During the progression of breast cancer
    Biochemical Pharmacology, 2006
    Co-Authors: Hong Jin Lee, Catherine Goodman, Hubert Maehr, Milan Uskokovic, Michael Reiss, Hao Liu, Daniel A Notterman, Nanjoo Suh
    Abstract:

    Abstract We investigateD gene expression changes inDuceD by a novel Gemini Vitamin D 3 analog, RO-438-3582 (1α,25-DihyDroxy-20 S -21(3-hyDroxy-3-methyl-butyl)-23-yne-26,27-hexafluoro-cholecalciferol, Ro3582), in a unique human breast MCF10 moDel. We useD two breast epithelial cell lines from this moDel, namely MCF10AT1 ( Ha-ras oncogene transfecteD MCF10A, early premalignant) anD MCF10CA1a (fully malignant anD metastatic DeriveD from the MCF10AT1 line). We analyzeD gene expression changes inDuceD by Ro3582 using GeneChip technology, quantitative RT-PCR, Western blot analysis, or a gene transcription assay. Interestingly, we founD Distinct gene expression profile Differences between Ro3582-inDuceD response of the early premalignant MCF10AT1 anD the malignant anD metastatic MCF10CA1a cell lines. Moreover, while the Gemini Vitamin D 3 analog Ro3582 moDulateD the expression of several Vitamin D target genes such as the 24-hyDroxylase, CD14, osteocalcin, anD osteopontin in both cell lines, Ro3582 regulateD many genes involveD in cell proliferation anD apoptosis, cell aDhesion, invasion, angiogenesis as well as cell signaling pathways, such as the BMP anD TGF-β systems, Differently in the two cell lines. The Gemini Vitamin D 3 analog Ro3582 inDuceD more significant gene changes in the early premalignant MCF10AT1 cells than in the malignant metastatic MCF10CA1a cells, suggesting that Gemini Vitamin D 3 analogs may be more effective in preventing the progression of an early stage of breast carcinogenesis than in treating late stage breast cancer.

  • a novel Vitamin D Derivative activates bone morphogenetic protein signaling in mcf10 breast epithelial cells
    Molecular Pharmacology, 2006
    Co-Authors: Hong Jin Lee, Andrew Wislocki, Catherine Goodman, Hubert Maehr, Milan Uskokovic, Michael Reiss, Nanjoo Suh
    Abstract:

    We investigateD the action of 1alpha,25-DihyDroxyVitamin D(3) [1alpha,25(OH)(2)D(3)], a novel Gemini Vitamin D(3) analog Ro-438-3582 [1alpha,25-DihyDroxy-20S-21(3-hyDroxy-3-methyl-butyl)-23-yne-26,27-hexafluorocholecalciferol (Ro3582)], anD a classic Vitamin D(3) analog Ro-26-2198 [1alpha,25-DihyDroxy-16,23(Z)-Diene-26,27-hexafluoro-19-nor-cholecalciferol (Ro2198)] in moDulating the transforming growth factor-beta (TGF-beta)/bone morphogenetic protein (BMP) system in MCF10 immortalizeD breast epithelial cells. We founD that 1alpha,25(OH)(2)D(3), Ro3582, anD Ro2198 all enhanceD BMP/SmaD signaling by increasing the phosphorylation of receptor-regulateD SmaDs. Ro3582 was more active than Ro2198, but both were consiDerably more active than 1alpha,25(OH)(2)D(3.) Ro3582 enhanceD BMP/SmaD signaling by 1) inDucing the phosphorylation of receptor-regulateD SmaDs (SmaD1/5), 2) increasing the accumulation of phosphorylateD SmaD1/5 in the nucleus, anD 3) activating BMP-meDiateD transcription in MCF10 breast epithelial cells. Furthermore, Ro3582 inDuceD the synthesis of BMP-2 anD BMP-6 mRNA anD protein, anD the expression of SmaD6 mRNA in MCF10 breast epithelial cells was inhibiteD by Ro3582. The inDuction of phospho-SmaD1/5 by Ro3582 was inhibiteD by treatment with the BMP antagonist Noggin, whereas neutralizing antiboDy to TGF-beta DiD not block the inDuction of phospho-SmaD1/5 by Ro3582. Treatment with Noggin also blockeD the effect of Ro3582 on nuclear accumulation of phospho-SmaD1/5 anD the inDuction of BMP-2 anD BMP-6 mRNA synthesis. These results inDicate that the activation of BMP/SmaD signaling by the Gemini Vitamin D(3) analog Ro3582 may be through the proDuction of BMP liganDs, incluDing BMP-2 anD BMP-6, anD/or Down-regulation of the inhibitory SmaD6. This is the first report to show that 1alpha,25(OH)(2)D(3) anD its Derivatives activate BMP/SmaD-specific signaling in human breast epithelial cells.

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