Home About us Contact
|
Home About us Contact | ||
|
|
||
RA Treatment (ra + treatment)
Selected AbstractsA Novel Gel Formulation of 0.25% Tretinoin and 1.2% Clindamycin Phosphate: Efficacy in Acne Vulgaris Patients Aged 12 to 18 YearsPEDIATRIC DERMATOLOGY, Issue 3 2009Lawrence F. Eichenfield M.D. Recently, the US FDA approved the combination of 1.2% clindamycin (CLIN) and 0.025% tretinoin (RA) in a novel gel formulation for the treatment of mild to moderate acne, based on results from two 12-week, multicenter, double-blind Phase 3 trials in which patients were randomized to four treatment arms: CLIN/RA, CLIN, RA, and vehicle. The trials studied more than 4500 patients 12 years of age or older. In both trials, CLIN/RA gel produced significantly greater clinical improvements than vehicle or either monotherapy. CLIN/RA was safe and well tolerated in both trials and in a 52-week safety follow-up evaluation. The current study is a subgroup analysis that evaluates CLIN/RA's effects on acne lesion prevalence in 12- to 18-year-old patients with mild to severe baseline acne severity. CLIN/RA significantly reduced the number of inflammatory, noninflammatory, and total acne lesions after 12 weeks of treatment (p , 0.004) in 1,710 patients aged 12 to 18 years. Relatively greater improvements were seen following CLIN/RA treatment compared to CLIN or RA monotherapy, or the vehicle gel beginning as early as 2 weeks following treatment initiation. This novel CLIN/RA gel for treating acne is tolerable and safe and offers clinicians and teen aged patients a new and efficacious intervention for acne vulgaris. [Abstract amended after online publication date June 8, 2009] [source] Retinoic acid increases the length and volume density of ducts in the rat embryonic pancreasDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 2 2003Carene Erasmus In this study, the role of all -trans retinoic acid (RA) on the proliferation of rat embryonic pancreas ducts and on the proportion of insulin cells was investigated. All- trans RA (10,6 m) was added to Ham's F12. ITS serum-free medium in which 12.5 day rat dorsal pancreatic buds were cultured on Matrigel. Control explants were cultured on Matrigel in Ham's F12. ITS alone or in Ham's F12. ITS containing ethanol (the diluent for RA). After a 7 day culture period, explants were incubated with bromodeoxyuridine (BrdU) for assessment of cell proliferation. Explants were processed for both morphometry and immunocytochemistry. The length density and volume density of the pancreatic ducts were assessed using an image analysis system. Cells positive for insulin, BrdU and glucagon were localized on adjacent serial sections. RA treatment caused a statistically significant increase in the volume density (P < 0.007) and length density (P < 0.008) of the ducts, as well as a 1.2-fold increase (P < 0.0001) in the proportion of insulin to glucagon cells, compared to both control groups. Few insulin cells were BrdU positive, indicating that cells had a low proliferation rate. The increased proportion of insulin cells may relate to the increased volume density and length density of the ducts in RA-treated explants. It is suggested that RA stimulated the production of additional progenitor cells and not proliferation of existing insulin cells. [source] Effects of retinoic acid upon eye field morphogenesis and differentiationDEVELOPMENTAL DYNAMICS, Issue 3 2001Gerald W. Eagleson Abstract This study describes a whole embryo and embryonic field analysis of retinoic acid's (RA) effects upon Xenopus laevis forebrain development and differentiation. By using in situ and immunohistochemical analysis of pax6, Xbf1, and tyrosine hydroxylase (TH), gene expression during eye field, telencephalon field, and retinal development was followed with and without RA treatment. These studies indicated that RA has strong effects upon embryonic eye and telencephalon field development with greater effects upon the ventral development of these organ fields. The specification and determination of separate eye primordia occurred at stage-16 when the prechordal plate reaches its most anterior aspect in Xenopus laevis. Differentiation of the dopaminergic cells within the retina was also affected in a distinct dorsoventral pattern by RA treatment, and cell type differentiation in the absence of distinct retinal laminae was also observed. It was concluded that early RA treatments affected organ field patterning by suppression of the upstream elements required for organ field development, and RA's effects upon cellular differentiation occur downstream to these organ determinants' expression within a distinct dorsoventral pattern. © 2001 Wiley-Liss, Inc. [source] Retinoic acid regulates the expression of PBX1, PBX2, and PBX3 in P19 cells both transcriptionally and post-translationallyJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2004Pu Qin Abstract Pre-B cell leukemia transcription factors (PBXs) are important co-factors for the transcriptional regulation mediated by a number of Hox proteins during embryonic development. It was previously shown that the expression of several Pbx genes is elevated in mouse embryo limb buds and embryonal carcinoma P19 cells upon retinoic acid (RA) treatment although the mechanism of this induction is not well understood. In this report, we demonstrate that PBX1a, PBX1b, PBX2, and PBX3 mRNAs and PBX1/2/3 proteins are induced during endodermal and neuronal differentiation of P19 cells in a RAR-dependent subtype-unspecific manner following RA treatment. The increases in both PBX1 mRNA and PBX3 mRNA levels are secondary responses to RA treatment requiring new proteins synthesis while the increase in PBX2 mRNA is a primary response. The RA-dependent increases in PBX1 mRNA, PBX2 mRNA, and PBX3 mRNA levels are likely to be transcriptionally regulated since the stability of these mRNAs does not change. In addition, the half-lives of PBX1/2/3 proteins are significantly extended by RA treatment. Two possible mechanisms could contribute to the stabilization of PBX proteins: PBX proteins associate with RA-dependent increased levels of MEIS proteins, and RA may decrease the proteasome dependent degradation of PBX proteins. © 2004 Wiley-Liss, Inc. [source] Retinoic acid induces expression of the interleukin-1, gene in cultured normal human mammary epithelial cells and in human breast carcinoma linesJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2002Limin Liu Retinoic acid (RA) and its derivatives inhibit the proliferation of normal human mammary epithelial cells (HMEC) and some breast carcinoma lines by mechanisms which are not fully understood. To identify genes that mediate RA-induced cell growth arrest, an HMEC cDNA library was synthesized and subtractive screening was performed. We identified the interleukin-1, (IL-1,) gene as an RA induced gene in HMEC. Northern blot analyses showed that the IL-1, gene was up-regulated as early as 2 h after RA treatment. Results from the treatment of HMEC with cycloheximide and actinomycin D indicated that the regulation of the IL-1, gene by RA occurred at the transcriptional level and that the IL-1, gene is a direct, downstream target gene of RA. To evaluate the effects of IL-1, on cell proliferation, the proliferation of HMEC was measured in the presence of RA or IL-1,, or both. Either RA or IL-1, could significantly inhibit the proliferation of HMEC. However, the addition of soluble IL-1 receptor antagonist (sIL-1ra) to the cell culture medium did not block RA-induced HMEC growth inhibition, whereas sIL-1ra did block the growth inhibition of HMEC by IL-1,. IL-1, expression was not observed in the three carcinoma cell lines, MCF-7, MDA-MB-231, and MDA-MB-468, as compared to the HMEC. Growth curves of the breast carcinoma cell lines showed strong inhibitory effects of RA and IL-1, on the growth of the estrogen receptor (ER) positive MCF-7 cell line, but only a small effect on the ER negative MDA-MB-231 cells. The expression of the IL-1, gene was also transcriptionally activated by RA in normal epithelial cells of prostate and oral cavity. Our results suggest that: (a) the IL-1, gene is a primary target of RA receptors in HMEC; (b) the enhanced expression of the IL-1, gene does not mediate the RA-induced growth arrest of HMEC; and (c) the expression of the IL-1, gene is low or absent in all three human breast carcinoma cell lines examined, but the defect in the IL-1, signaling pathway may be different in ER positive versus ER negative carcinoma cells. © 2002 Wiley-Liss, Inc. [source] Implication of the proprotein convertase NARC-1/PCSK9 in the development of the nervous systemJOURNAL OF NEUROCHEMISTRY, Issue 3 2006Steve Poirier Abstract Neural apoptosis-regulated convertase-1/proprotein convertase subtilisin-kexin like-9 (NARC-1/PCSK9) is a proprotein convertase recently described to play a major role in cholesterol homeostasis through enhanced degradation of the low-density lipoprotein receptor (LDLR) and possibly in neural development. Herein, we investigated the potential involvement of this proteinase in the development of the CNS using mouse embryonal pluripotent P19 cells and the zebrafish as models. Time course quantitative RT,PCR analyses were performed following retinoic acid (RA)-induced neuroectodermal differentiation of P19 cells. Accordingly, the mRNA levels of NARC-1/PCSK9 peaked at day 2 of differentiation and fell off thereafter. In contrast, the expression of the proprotein convertases subtilisin kexin isozyme 1/site 1 protease and Furin was unaffected by RA, whereas that of PC5/6 and PC2 increased within and/or after the first 4 days of the differentiation period respectively. This pattern was not affected by the cholesterogenic transcription factor sterol regulatory element-binding protein-2, which normally up-regulates NARC-1/PCSK9 mRNA levels in liver. Furthermore, in P19 cells, RA treatment did not affect the protein level of the endogenous LDLR. This agrees with the unique expression pattern of NARC-1/PCSK9 in the rodent CNS, including the cerebellum, where the LDLR is not significantly expressed. Whole-mount in situ hybridization revealed that the pattern of expression of zebrafish NARC-1/PCSK9 is similar to that of mouse both in the CNS and periphery. Specific knockdown of zebrafish NARC-1/PCSK9 mRNA resulted in a general disorganization of cerebellar neurons and loss of hindbrain,midbrain boundaries, leading to embryonic death at ,,96 h after fertilization. These data support a novel role for NARC-1/PCSK9 in CNS development, distinct from that in cholesterogenic organs such as liver. [source] Improving patient outlook in rheumatoid arthritis: Experience with abataceptJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 10 2008MA (Nurse Manager), Mary Coughlin RN Abstract Purpose: To examine the importance of improving patient outlook in rheumatoid arthritis (RA) and to discuss the role of the nurse practitioner (NP) who, through the assessment of patient-reported outcomes and in acting as an advocate for the patient with the wider healthcare team, has a crucial part to play in managing the overall well-being of the patient. This article will draw on the clinical experience to date with abatacept, a first-in-class therapy that has been approved for the treatment of RA in patients with an inadequate response to either traditional disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, or biological DMARDs, such as tumor necrosis factor-, antagonists. Data sources: A comprehensive literature search was performed using the National Library of Medicine (MEDLINE), EMBASE, and BIOSIS databases (restricted to articles posted between January 2000 and February 2007) with the search terms CTLA-4Ig, abatacept, and primary clinical trial publications in patients with RA. The clinical data are summarized in this review along with safety data presented in the prescribing information. Conclusions: Recent changes in the approach to RA treatment, particularly the advent of biological therapies, have impacted the role of the NP. The role of the NP is integral to the management of RA and in maximizing patient outcomes, through educating patients to make informed choices regarding their treatment, ensuring the safe administration of therapies and monitoring response to therapy, and in acting as an advocate for the patient within the wider healthcare team. Implications for practice: The use of more patient-centered measures of response are gaining increasing importance both in clinical trials and in clinical practice, and as such the NP has an important role in ensuring that both the physical and the psychological needs of patients are met. Clinical trials to date have shown that abatacept provides significant and clinically meaningful improvements in patient-reported outcomes, as well as demonstrating significant clinical benefits and a consistent safety profile, thus representing a valuable treatment option within the RA treatment armamentarium. [source] Skeletal and Pigmentation Defects following Retinoic Acid Exposure in Larval Summer Flounder, Paralichthys dentatusJOURNAL OF THE WORLD AQUACULTURE SOCIETY, Issue 3 2007Gabriela M. Martinez Supplementation of larval diets with vitamin A (VA) is routinely and successfully used to stimulate pigmentation development in hatchery-reared flatfishes. However, excess dietary VA can lead to high levels of its metabolite retinoic acid (RA) and has been associated with the occurrence of skeletal deformities, presumably via RA toxicity. We reared summer flounder larvae, Paralichthys dentatus, in water containing 0- to 20-nM RA to assess its effects on postmetamorphic pigmentation and on skeletal development. RA exposure disrupted pigmentation development: treated tanks had a smaller percentage of normally pigmented fish than did controls, with increased numbers of both hypo- and hyperpigmented individuals. Exposure also affected the development of several skeletal features: RA treatment correlated with a significant increase in the severity of defects in jaws, fins, hypurals, and vertebrae compared with control groups. [source] Activation of synoviolin promoter in rheumatoid synovial cells by a novel transcription complex of interleukin enhancer binding factor 3 and GA binding protein ,ARTHRITIS & RHEUMATISM, Issue 1 2009Toshihiko Izumi Objective Synoviolin is an E3 ubiquitin ligase, and its overexpression is implicated in the pathogenesis of rheumatoid arthritis (RA). We reported previously that Ets binding site 1 (EBS-1) within the synoviolin promoter is crucial for the expression of synoviolin, and GA binding protein (GABP) binds to this site. This study was undertaken to elucidate the precise mechanisms of transcriptional regulation via EBS-1. Methods We performed purification and identification of complex components that bind to EBS-1 and inspected their contributions to the transcriptional regulation of synoviolin in rheumatoid synovial cells. We biochemically purified proteins that had EBS-1 binding activity and identified the proteins using liquid chromatography tandem mass spectrometry analysis. The identified proteins were verified to recruit and form the complex on EBS-1 using electrophoretic mobility shift assay and coimmunoprecipitation assay. Furthermore, their transcription activities were tested by reporter assays and RNA interference experiments. Results We identified interleukin enhancer binding factor 3 (ILF-3) as a novel factor in the complex. ILF-3 was demonstrated to activate the synoviolin promoter via association with GABP, in rheumatoid synovial cells. In addition, further activation was observed with ILF-2 and GABP,, previously reported interactants of ILF-3 and GABP,, respectively. Moreover, ILF-3,knockdown experiments showed reduced expression of the synoviolin gene. Conclusion Our findings indicate that ILF-3, which has been known to regulate IL-2 expression in T cells, up-regulates synoviolin expression with GABP, in rheumatoid synovial cells. ILF-3 might be a target for RA treatment through its effect on IL-2 in T cells and synoviolin in rheumatoid synovial cells. [source] Effects of retinoic acid upon eye field morphogenesis and differentiationDEVELOPMENTAL DYNAMICS, Issue 3 2001Gerald W. Eagleson Abstract This study describes a whole embryo and embryonic field analysis of retinoic acid's (RA) effects upon Xenopus laevis forebrain development and differentiation. By using in situ and immunohistochemical analysis of pax6, Xbf1, and tyrosine hydroxylase (TH), gene expression during eye field, telencephalon field, and retinal development was followed with and without RA treatment. These studies indicated that RA has strong effects upon embryonic eye and telencephalon field development with greater effects upon the ventral development of these organ fields. The specification and determination of separate eye primordia occurred at stage-16 when the prechordal plate reaches its most anterior aspect in Xenopus laevis. Differentiation of the dopaminergic cells within the retina was also affected in a distinct dorsoventral pattern by RA treatment, and cell type differentiation in the absence of distinct retinal laminae was also observed. It was concluded that early RA treatments affected organ field patterning by suppression of the upstream elements required for organ field development, and RA's effects upon cellular differentiation occur downstream to these organ determinants' expression within a distinct dorsoventral pattern. © 2001 Wiley-Liss, Inc. [source] | |||||||||||||