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Clinical and Experimental Dermatology Mar 2017Treatment of severe hand eczema (HE) that is resistant to topical potent corticosteroid treatment is challenging. In 2013, we surveyed 194 UK dermatologists to obtain...
Treatment of severe hand eczema (HE) that is resistant to topical potent corticosteroid treatment is challenging. In 2013, we surveyed 194 UK dermatologists to obtain information about their usual treatment pathways to inform the choice of the comparator in a trial of alitretinoin in severe HE (ALPHA trial); the results indicated that the treatment approaches favoured by UK dermatologists differ. Psoralen combined with ultraviolet A (PUVA) and alitretinoin were identified as the most frequent first-line treatment options for hyperkeratotic HE, whereas oral corticosteroids were identified as the most frequent first-line treatment for vesicular HE, followed by PUVA and alitretinoin. In terms of potential adverse effects of long-term or repeated use, oral steroids and ciclosporin A were reported to cause most concern. There is uncertainty about which treatment gives the best short and long-term outcomes, because of a lack of definitive randomised controlled trials evaluating the effectiveness of different treatment pathways in severe HE.
Topics: Administration, Oral; Adrenal Cortex Hormones; Alitretinoin; Chronic Disease; Dermatologists; Eczema; Hand Dermatoses; Health Care Surveys; Humans; Keratolytic Agents; PUVA Therapy; Practice Patterns, Physicians'; Tretinoin; United Kingdom
PubMed: 27910127
DOI: 10.1111/ced.13015 -
Journal of Medical Virology Jan 2023Multiple treatment modalities for Kaposi sarcoma (KS) have been reported, including chemotherapy, radiation therapy, surgical excision, electrochemotherapy, and...
Multiple treatment modalities for Kaposi sarcoma (KS) have been reported, including chemotherapy, radiation therapy, surgical excision, electrochemotherapy, and cryotherapy. Common topical treatments include timolol, imiquimod, and alitretinoin. We searched our institutional database for patients with ICD-9 or 10 codes for KS seen by a dermatologist with experience in KS management from July 1, 2004 to January 1, 2022. We screened patient charts to include patients who received combination therapy of cryotherapy followed by topical imiquimod three times a week for 2 months (n = 9). Patients were followed in the clinic every 3 months. Time to resolution was assessed by photographic evidence of resolution as determined by a dermatologist and corroborated with clinical documentation in patient charts. Median age (IQR) at KS diagnosis was 58 (27.5) years. All patients were male (n = 9, 100%). Majority were white (n = 7, 78%) and non-Hispanic (n = 8, 89%). Five (56%) had classic KS, one (11%) had HIV-associated KS, and three (33%) were HIV-negative men who have sex with men. Median time to resolution was 30.5 weeks, with a median of two treatments. In our study, 93% (n = 42/45) of lesions and 89% (n = 8/9) of patients experienced complete resolution during a median (range) duration of follow-up of 58 (13-209) weeks. Side effects were limited to pain during cryotherapy, occasional blister formation after cryotherapy, and mild inflammation due to imiquimod. No infections were observed. Combination therapy of cryotherapy and topical imiquimod may be an efficacious and comparatively low-risk treatment for limited, cutaneous KS.
Topics: Humans; Male; Middle Aged; Female; Imiquimod; Sarcoma, Kaposi; Homosexuality, Male; Sexual and Gender Minorities; Cryotherapy; Skin Neoplasms; Immunotherapy; HIV Infections
PubMed: 36504005
DOI: 10.1002/jmv.28396 -
Scientific Reports Jul 2017The purpose of this study was to examine the neurorestorative effect of delayed 9 cis retinoic acid (9cRA) treatment for stroke. Adult male rats received a 90-min right...
The purpose of this study was to examine the neurorestorative effect of delayed 9 cis retinoic acid (9cRA) treatment for stroke. Adult male rats received a 90-min right distal middle cerebral artery occlusion (dMCAo). Animals were separated into two groups with similar infarction sizes, based on magnetic resonance imaging on day 2 after dMCAo. 9cRA or vehicle was given via an intranasal route daily starting from day 3. Stroke rats receiving 9cRA post-treatment showed an increase in brain 9cRA levels and greater recovery in motor function. 9cRA enhanced the proliferation of bromodeoxyuridine (+) cells in the subventricular zone (SVZ) and lesioned cortex in the stroke brain. Using subventricular neurosphere and matrigel cultures, we demonstrated that proliferation and migration of SVZ neuroprogenitor cells were enhanced by 9cRA. Our data support a delayed and non-invasive drug therapy for stroke. Intranasal 9cRA can facilitate the functional recovery and endogenous repair in the ischemic brain.
Topics: Alitretinoin; Animals; Body Weight; Bone Morphogenetic Protein 7; Cell Movement; Cell Proliferation; Cerebral Cortex; Disease Models, Animal; Immunohistochemistry; Lateral Ventricles; Magnetic Resonance Imaging; Male; Motor Activity; Rats; Stroke
PubMed: 28674431
DOI: 10.1038/s41598-017-04048-2 -
Acta Dermatovenerologica Alpina,... Dec 2023Darier disease is a rare autosomal dominant genodermatosis that initially first presents in adolescence with scaly reddish brown keratotic papules and plaques with a...
Darier disease is a rare autosomal dominant genodermatosis that initially first presents in adolescence with scaly reddish brown keratotic papules and plaques with a seborrheic and intertriginous distribution. The absence of specific targeted medications complicates the treatment process, and managing resistant cases can prove challenging due to recurrent exacerbations that may result in serious complications such as secondary bacterial and viral infections. Treatments of choice include antiseptics, topical corticosteroids, and systemic retinoids, mainly acitretin and isotretinoin. We report the case of a female patient with Darier disease that was unsuccessfully treated with acitretin and isotretinoin but showed significant improvement with alitretinoin. Previous reports on the efficacy of alitretinoin in Darier disease are reviewed.
Topics: Adolescent; Humans; Female; Darier Disease; Alitretinoin; Acitretin; Isotretinoin; Dermatologic Agents
PubMed: 38126103
DOI: No ID Found -
Rhode Island Medical Journal (2013) Aug 2023Kaposi sarcoma is a rare vascular malignancy associated with HHV-8 infection. Four variants of Kaposi sarcoma have been described: Classic, African, HIV-associated, and...
Kaposi sarcoma is a rare vascular malignancy associated with HHV-8 infection. Four variants of Kaposi sarcoma have been described: Classic, African, HIV-associated, and iatrogenic. Iatrogenic Kaposi sarcoma is typically associated with immunosuppression and organ transplantation. We present a case of iatrogenic Kaposi sarcoma associated with tofacitinib therapy. A 69-year-old woman with rheumatoid arthritis receiving tofacitinib presented with multiple firm, purple-red nodules and brown plaques on the left lower extremity and a single lesion on the right medial calf. Clinicopathologic correlation confirmed a diagnosis of Kaposi sarcoma. Tofacitinib was discontinued and she was started on Alitretinoin 0.1% gel bid. The purple-red Kaposi sarcoma nodules decreased 50% in size after 4 months and resolved at 1 year off the tofacitinib and initiation of alitretinoin gel. As the use of immunomodulators and biologics continues to expand, awareness of this association is important for prompt diagnosis and management.
Topics: Female; Humans; Aged; Sarcoma, Kaposi; Alitretinoin; Arthritis, Rheumatoid; Iatrogenic Disease
PubMed: 37494621
DOI: No ID Found -
Biochimica Et Biophysica Acta May 2011Cellular retinol binding-protein I (CRBPI) and cellular retinol binding-protein II (CRBPII) serve as intracellular retinoid chaperones that bind retinol and retinal with...
BACKGROUND
Cellular retinol binding-protein I (CRBPI) and cellular retinol binding-protein II (CRBPII) serve as intracellular retinoid chaperones that bind retinol and retinal with high affinity and facilitate substrate delivery to select enzymes that catalyze retinoic acid (RA) and retinyl ester biosynthesis. Recently, 9-cis-RA has been identified in vivo in the pancreas, where it contributes to regulating glucose-stimulated insulin secretion. In vitro, 9-cis-RA activates RXR (retinoid × receptors), which serve as therapeutic targets for treating cancer and metabolic diseases. Binding affinities and structure-function relationships have been well characterized for CRBPI and CRBPII with all-trans-retinoids, but not for 9-cis-retinoids. This study extended current knowledge by establishing binding affinities for CRBPI and CRBPII with 9-cis-retinoids.
METHODS
We have determined apparent dissociation constants, K'(d), through monitoring binding of 9-cis-retinol, 9-cis-retinal, and 9-cis-RA with CRBPI and CRBPII by fluorescence spectroscopy, and analyzing the data with non-linear regression. We compared these data to the data we obtained for all-trans- and 13-cis-retinoids under identical conditions.
RESULTS
CRBPI and CRBPII, respectively, bind 9-cis-retinol (K'(d), 11nM and 68nM) and 9-cis-retinal (K'(d), 8nM and 5nM) with high affinity. No significant 9-cis-RA binding was observed with CRBPI or CRBPII.
CONCLUSIONS
CRBPI and CRBPII bind 9-cis-retinol and 9-cis-retinal with high affinities, albeit with affinities somewhat lower than for all-trans-retinol and all-trans-retinal.
GENERAL SIGNIFICANCE
These data provide further insight into structure-binding relationships of cellular retinol binding-proteins and are consistent with a model of 9-cis-RA biosynthesis that involves chaperoned delivery of 9-cis-retinoids to enzymes that recognize retinoid binding-proteins.
Topics: Algorithms; Alitretinoin; Animals; Binding, Competitive; Diterpenes; Fluorometry; Humans; Kinetics; Protein Binding; Retinaldehyde; Retinoid X Receptors; Retinol-Binding Proteins, Cellular; Tretinoin; Vitamin A
PubMed: 21382444
DOI: 10.1016/j.bbagen.2011.02.009 -
Cancer Letters Mar 2020Radiation therapy is a common treatment for prostate cancer, however recurrence remains a problem. MicroRNA expression is altered in prostate cancer and may promote...
Radiation therapy is a common treatment for prostate cancer, however recurrence remains a problem. MicroRNA expression is altered in prostate cancer and may promote therapy resistance. Through bioinformatic analyses of TCGA and CPC-GENE patient cohorts, we identified higher miR-191 expression in tumor versus normal tissue, and increased expression in higher Gleason scores. In vitro and in vivo experiments demonstrated that miR-191 overexpression promotes radiation survival, and contributes to a more aggressive phenotype. Retinoid X receptor alpha, RXRA, was discovered to be a novel target of miR-191, and knockdown recapitulated radioresistance. Furthermore, treatment of prostate cancer cells with the RXRA agonist 9-cis-retinoic acid restored radiosensitivity. Supporting this relationship, patients with high miR-191 and low RXRA abundance experienced quicker biochemical recurrence. Reduced RXRA translated to a higher risk of distant failure after radiotherapy. Notably, this miR-191/RXRA interaction was conserved in a novel primary cell line derived from radiorecurrent prostate cancer. Together, our findings demonstrate that miR-191 promotes prostate cancer survival after radiotherapy, and highlights retinoids as a potential option to improve radiotherapy response.
Topics: Alitretinoin; Animals; Antineoplastic Agents; Biomarkers, Tumor; Cell Line, Tumor; Chemoradiotherapy, Adjuvant; Disease-Free Survival; Down-Regulation; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; Kallikreins; Kaplan-Meier Estimate; Male; Mice; MicroRNAs; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local; Primary Cell Culture; Prognosis; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiation Tolerance; Retinoid X Receptor alpha; Survival Rate; Time Factors; Xenograft Model Antitumor Assays
PubMed: 31874245
DOI: 10.1016/j.canlet.2019.12.025 -
Dermatology Online Journal Jul 2019Interstitial granulomatous drug reaction is a rare condition presenting as erythematous-to-violaceous plaques on the lateral trunk, axillae, buttocks, and thighs....
Interstitial granulomatous drug reaction is a rare condition presenting as erythematous-to-violaceous plaques on the lateral trunk, axillae, buttocks, and thighs. Calcium-channel blockers, angiotensin converting enzyme inhibitors, beta-blockers, and statins have been described as drugs that can trigger interstitial granulomatous drug reaction. We present a case of interstitial granulomatous drug reaction related to hydrochlorothiazide and our approach to management of this condition. The diagnosis was confirmed with a skin biopsy and a rechallenge of hydrochlorothiazide, which exacerbated the patient's symptoms. The patient improved significantly with rigorous photoprotection, combination dapsone-alitretinoin therapy, and discontinuation of hydrochlorothiazide.
Topics: Aged; Biopsy; Dermatitis, Photoallergic; Diuretics; Drug Eruptions; Granuloma; Humans; Hydrochlorothiazide; Male; Sodium Chloride Symporter Inhibitors
PubMed: 31450282
DOI: No ID Found -
The Journal of Biological Chemistry Apr 2003The ATP-binding cassette transporter A1 (ABCA1) is a major regulator of peripheral cholesterol efflux and plasma high density lipoprotein metabolism. In adult rat brain...
22R-hydroxycholesterol and 9-cis-retinoic acid induce ATP-binding cassette transporter A1 expression and cholesterol efflux in brain cells and decrease amyloid beta secretion.
The ATP-binding cassette transporter A1 (ABCA1) is a major regulator of peripheral cholesterol efflux and plasma high density lipoprotein metabolism. In adult rat brain we found high expression of ABCA1 in neurons in the hypothalamus, thalamus, amygdala, cholinergic basal forebrain, and hippocampus. Large neurons of the cholinergic nucleus basalis together with CA1 and CA3 pyramidal neurons were among the most abundantly immunolabeled neurons. Glia cells were largely negative. Because cholesterol homeostasis may have an essential role in central nervous system function and neurodegeneration, we examined ABCA1 expression and function in different brain cell types using cultures of primary neurons, astrocytes, and microglia isolated from embryonic rat brain. The basal ABCA1 mRNA and protein levels detected in these cell types were increased markedly after exposure to oxysterols and 9-cis-retinoic acid, which are ligands for the nuclear hormone liver X receptors and retinoic X receptors, respectively. Functionally, the increased ABCA1 expression caused by these ligands was followed by elevated apoA-I- and apoE-specific cholesterol efflux in neurons and glia. In non-neuronal and neuronal cells overexpressing a human Swedish variant of amyloid precursor protein, 22R-hydroxycholesterol and 9-cis-retinoic acid induced ABCA1 expression and increased apoA-I-mediated cholesterol efflux consequently decreasing cellular cholesterol content. More importantly, we demonstrated that these ligands alone or in combination with apoA-I caused a substantial reduction in the stability of amyloid precursor protein C-terminal fragments and decreased amyloid beta production. These effects of 22R-hydroxycholesterol may provide a novel strategy to decrease amyloid beta secretion and consequently reduce the amyloid burden in the brain.
Topics: ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters; Alitretinoin; Amyloid beta-Peptides; Animals; Animals, Newborn; Brain; Cells, Cultured; Cerebral Cortex; Cholesterol; Embryo, Mammalian; Gene Expression Regulation; Hippocampus; Hydroxycholesterols; Kinetics; Ligands; Microglia; Neurons; Organ Specificity; Protein Biosynthesis; Pyramidal Cells; RNA, Messenger; Rats; Rats, Sprague-Dawley; Transcription, Genetic; Tretinoin
PubMed: 12547833
DOI: 10.1074/jbc.M300044200 -
Acta Dermato-venereologica Sep 2022This non-interventional, observational, longitudinal study describes treatment patterns of atopic dermatitis (AD) in Sweden. Data from 3 Swedish registries were merged,... (Observational Study)
Observational Study
This non-interventional, observational, longitudinal study describes treatment patterns of atopic dermatitis (AD) in Sweden. Data from 3 Swedish registries were merged, and included patients who received an AD diagnosis (during the period 1997 to 2019) and had AD treatment prescribed (during the period 2006 to 2020). Treatment persistence, treatment sequencing, time-to-event analysis, and 12-month prevalence were analysed. Overall, data for 99,885 patients with AD were included, of whom 4,086 (4.1%) received systemic treatments. Median persistence rates were 12.6 (95% CI 11.9, 13.4) months for methotrexate, 10.8 (9.1, 13.0) months for azathioprine, 5.6 (3.8, 6.2) months for mycophenolate, 5.1 (4.4, 5.7) months for alitretinoin and 3.4 (3.2, 3.7) months for cyclosporine. Median (Q1, Q3) time from first secondary care visit for AD to first systemic treatment was 5.8 (2.2, 11.0) years overall and 4.4 (1.3, 9.1) years in the Stockholm region. Methotrexate was a prominent first- and second-line treatment used during the period 2006 to 2020. Dupilumab was introduced during the study period and was increasingly used as first- or second-line therapy over time. The 12-month prevalence of AD generally remained steady, with a gradual increase observed over time for the overall population. A steep increase was observed in Stockholm from 2011. This study shows that a small proportion of patients with AD are offered systemic treatments in Sweden, with long periods in secondary care prior to systemic treatments and low persistence on systemic treatments. Regional differences highlight a need for national treatment guidelines.
Topics: Dermatitis, Atopic; Humans; Longitudinal Studies; Methotrexate; Retrospective Studies; Secondary Care; Sweden
PubMed: 35818736
DOI: 10.2340/actadv.v102.1986