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The Lancet. Rheumatology Feb 2024Sarcoidosis is an inflammatory condition that can affect various organs and tissues, causing the formation of granulomas and subsequent functional impairment. The origin... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Sarcoidosis is an inflammatory condition that can affect various organs and tissues, causing the formation of granulomas and subsequent functional impairment. The origin of sarcoidosis remains unknown and there are few treatment options. Mechanistic target of rapamycin (mTOR) activation is commonly seen in granulomas of patients across different tissues and has been shown to induce sarcoidosis-like granulomas in a mouse model. This study aimed to examine the efficacy and safety of the mTOR inhibitor sirolimus as a treatment for cutaneous sarcoidosis.
METHODS
We did a single-centre, randomised study treating patients with persistent and glucocorticoid-refractory cutaneous sarcoidosis with sirolimus at the Vienna General Hospital, Medical University of Vienna (Vienna, Austria). We recruited participants who had persistent, active, and histologically proven cutaneous sarcoidosis. We used an n-of-1 crossover design in a placebo-controlled, double-blind topical treatment period and a subsequent single-arm systemic treatment phase for 4 months in the same participants. Participants initially received either 0·1% topical sirolimus in Vaseline or placebo (Vaseline alone), twice daily. After a washout period, all participants were subsequently administered a 6 mg loading dose followed by 2 mg sirolimus solution orally once daily, aiming to achieve serum concentrations of 6 ng/mL. The primary endpoint was change in the Cutaneous Sarcoidosis Activity and Morphology Index (CSAMI) after topical or systemic treatment. All participants were included in the safety analyses, and patients having completed the respective treatment period (topical treatment or systemic treatment) were included in the primary analyses. Adverse events were assessed at each study visit by clinicians and were categorised according to their correlation with the study drug, severity, seriousness, and expectedness. This study is registered with EudraCT (2017-004930-27) and is now closed.
FINDINGS
16 participants with persistent cutaneous sarcoidosis were enrolled in the study between Sept 3, 2019, and June 15, 2021. Six (37%) of 16 participants were men, ten (63%) were women, and 15 (94%) were White. The median age of participants was 54 years (IQR 48-58). 14 participants were randomly assigned in the topical phase and 2 entered the systemic treatment phase directly. Daily topical treatment did not improve cutaneous lesions (effect estimate -1·213 [95% CI -2·505 to 0·079], p=0·066). Systemic treatment targeting trough serum concentrations of 6 ng/mL resulted in clinical and histological improvement of skin lesions in seven (70%) of ten participants (median -7·0 [95% CI -16·5 to -3·0], p=0·018). Various morphologies of cutaneous sarcoidosis, including papular, nodular, plaque, scar, and tattoo-associated sarcoidosis, responded to systemic sirolimus therapy with a long-lasting effect for more than 1 year after treatment had been stopped. There were no serious adverse events and no deaths.
INTERPRETATION
Short-term treatment with systemic sirolimus might be an effective and safe treatment option for patients with persistent glucocorticoid-refractory sarcoidosis with a long-lasting disease-modulating effect. The effect of sirolimus in granulomatous inflammation should be investigated further in large, multi-centre, randomised clinical trials.
FUNDING
Vienna Science and Technology Fund, Austrian Science Fund.
Topics: Female; Humans; Male; Middle Aged; Butylamines; Glucocorticoids; Granuloma; Petrolatum; Sarcoidosis; Sirolimus
PubMed: 38267106
DOI: 10.1016/S2665-9913(23)00302-8 -
Pharmaceutical Research Oct 2018Ophthalmic ointments are unique in that they combine features of topical drug delivery, the ophthalmic route and ointment (semisolid) formulations. Accordingly, these... (Review)
Review
Ophthalmic ointments are unique in that they combine features of topical drug delivery, the ophthalmic route and ointment (semisolid) formulations. Accordingly, these complex formulations are challenging to develop and evaluate and therefore it is critically important to understand their physicochemical properties as well as their in vitro drug release characteristics. Previous reports on the characterization of ophthalmic ointments are very limited. Although there are FDA guidance documents and USP monographs covering some aspects of semisolid formulations, there are no FDA guidance documents nor any USP monographs for ophthalmic ointments. This review summarizes the physicochemical and in vitro profiling methods that have been previously reported for ophthalmic ointments. Specifically, insight is provided into physicochemical characterization (rheological parameters, drug content and content uniformity, and particle size of the API in the finished ointments) as well as important considerations (membranes, release media, method comparison, release kinetics and discriminatory ability) in in vitro release testing (IVRT) method development for ophthalmic ointments. Graphical Abstract Summary of the physicochemcial profiling and in vitro drug release testing (IVRT) for ophthalmic ointments.
Topics: Administration, Ophthalmic; Administration, Topical; Animals; Drug Compounding; Drug Delivery Systems; Drug Liberation; Humans; Ointments; Particle Size; Petrolatum; Pharmaceutical Preparations; Rheology
PubMed: 30324424
DOI: 10.1007/s11095-018-2513-3 -
International Journal of Cosmetic... Aug 2018Petrolatum and soybean oil are common ingredients incorporated in topical skin formulations for skin protection and moisturization. However, the stratum corneum (SC)...
OBJECTIVES
Petrolatum and soybean oil are common ingredients incorporated in topical skin formulations for skin protection and moisturization. However, the stratum corneum (SC) penetration kinetics of these two cosmetic ingredients has not been systematically studied. Glyceryl monooleate (GlyMOle) has been shown to enhance skin penetration of various compounds. It was hypothesized that GlyMOle could enhance skin penetration of petrolatum and soybean oil. This study aimed to examine the in vitro skin penetration of petrolatum and soybean oil in the presence or absence of GlyMOle.
METHODS
Skin permeation experiments were conducted using the in vitro Franz diffusion cell model with split-thickness human skin and human epidermal membrane (HEM). The effect of permeant dose and the kinetics of permeant penetration were examined with and without GlyMOle in vitro.
RESULTS
Petrolatum and soybean oil were found to permeate across HEM, and no effect of GlyMOle on skin permeation into the receptor chamber was observed. GlyMOle enhanced the penetration of petrolatum into the split-thickness skin at 50 μg dose (petrolatum:GlyMOle, 49 : 1, w/w). However, no effect of GlyMOle on petrolatum penetration was observed at 200 μg dose (of the same petrolatum:GlyMOle ratio), indicating a dose-dependent effect. GlyMOle at the level used in the study did not enhance the penetration of soybean oil with 50 and 200 μg doses at any timepoints.
CONCLUSION
GlyMOle was a skin penetration enhancer for petrolatum under the in vitro conditions identified in this study.
Topics: Administration, Cutaneous; Glycerides; Humans; In Vitro Techniques; Petrolatum; Skin Absorption; Soybean Oil
PubMed: 29876949
DOI: 10.1111/ics.12469 -
International Journal of Cosmetic... Apr 2021An important trend in the personal care industry involves the development of body wash products that not only clean the skin without damage but deposit conditioning...
BACKGROUND
An important trend in the personal care industry involves the development of body wash products that not only clean the skin without damage but deposit conditioning ingredients to improve skin barrier function.
OBJECTIVE
The objective of this study was to develop skin biomarker measures to quantify the treatment effects of body wash products.
METHODS
We employed analysis of structural proteins (keratin 1,10,11 and involucrin), a natural moisturizing factor (pyrrolidone carboxylic acid) and an inflammatory mediator (IL-1ra/IL-1α) from adhesive discs with dry skin grading, TEWL and capacitance measurements to compare the effects of direct application of petrolatum, a high petrolatum depositing body wash, and a regular body wash on dry leg skin in a standard leg-wash treatment protocol.
RESULTS
High depositing body wash and petrolatum had positive effects on stratum corneum barrier function as judged by biomarker analysis, biophysical measurements and skin grading compared to the regular body wash product.
CONCLUSIONS
The results clearly indicate that a combination of biomarker and biophysical property measurements is effective for determining the skin benefits of moisturizing body wash products.
Topics: Adolescent; Adult; Aged; Biomarkers; Female; Humans; Middle Aged; Petrolatum; Skin; Young Adult
PubMed: 33336384
DOI: 10.1111/ics.12684 -
Clinical Rheumatology Jun 2018Autoimmune/inflammatory syndrome induced by adjuvant (ASIA) includes the following conditions: siliconosis, Gulf War syndrome, macrophagic myofasciitis syndrome, and... (Review)
Review
Autoimmune/inflammatory syndrome induced by adjuvant (ASIA) includes the following conditions: siliconosis, Gulf War syndrome, macrophagic myofasciitis syndrome, and post-vaccination phenomena. Afterward, other syndromes have been recognized, such as in ASIA by mineral oil (ASIA-MO). These conditions are triggered by adjuvants and they are the result of the interplay of genetic and environmental factors. ASIA-MO is defined as the infiltration of oily type modeling substances for cosmetic purposes. It has been reported in many countries and used surreptitiously. Pathogenesis of ASIA-MO is not clear, but is characterized by chronic granulomatous inflammation, like the pristane model in mice, with increase of proinflammatory cytokines: type I interferons (IFNα and IFNß), systemic lupus erythematosus (SLE), and erosive arthritis. In humans, an increase of interleukin 1 (IL-1) has been found. Clinical spectrum of ASIA-MO is heterogeneous, varying from mild to severe and being local and systemic. The systemic manifestations can be non-specific and specific, meeting criteria for any autoimmune disease (AID), i.e., SLE, rheumatoid arthritis, and systemic sclerosis, among others. The areas of the body where the mineral oil is mostly applied include the following: buttocks (38-72%), breasts (12-16%), lower extremities (18-22%), and face (6-10%). The penis augmentation is also common. Treatment is focused on local and systemic manifestations and requires medical and surgical management representing a challenge for the physician.
Topics: Animals; Autoimmune Diseases; Cosmetic Techniques; Humans; Mineral Oil
PubMed: 29619588
DOI: 10.1007/s10067-018-4078-2 -
International Dental Journal Oct 2022The aim of this work was to review the protocol of the use of silver diamine fluoride (SDF) for arresting caries, specifically the application time. (Review)
Review
OBJECTIVE
The aim of this work was to review the protocol of the use of silver diamine fluoride (SDF) for arresting caries, specifically the application time.
METHOD
Two researchers searched manufacturers' instructions, YouTube videos, and 5 databases (Embase, Medline, PubMed, Scopus, and Web of Science). Manufacturers' instructions, videos from national dental organisations, and peer-reviewed journal articles that published the SDF application protocol in English for arresting caries were selected.
RESULTS
The review included 14 protocols from 15 publications from 4 manufacturers, 3 dental associations, and 7 author teams (one team had 2 articles). The American Dental Association and the British Society of Paediatric Dentistry provided their SDF application protocols on YouTube. The American Academy of Paediatric Dentistry and 7 author teams published their protocols in journal articles. Seven publications suggested an SDF application time of 60 seconds. Seven publications suggested a time range of 10 seconds to 240 seconds. Two publications suggested caries excavation, but 4 publications suggested no caries excavation before SDF application. The procedures from at least 5 publications involved protecting the gingiva with petroleum jelly, isolating the carious tooth with cotton rolls, drying the carious lesion with a 3-in-1 syringe, applying SDF solution with a micro brush for 60 seconds, removing excess SDF solution with gauze, and applying fluoride varnish to the SDF-treated lesion.
CONCLUSIONS
Although the SDF application protocol is simple and straightforward, the published protocols could be different. Most publications suggested an SDF application time of 60 seconds, which can be long, particularly for young children and older adults.
Topics: Aged; Cariostatic Agents; Child; Child, Preschool; Dental Caries; Fluorides, Topical; Humans; Petrolatum; Quaternary Ammonium Compounds; Silver Compounds
PubMed: 35843730
DOI: 10.1016/j.identj.2022.06.006 -
Archives of Razi Institute Aug 2022Mineral oil as a barrier can minimize temperature, osmolality, and pH fluctuation of the media in the embryo production system (IVP). Regardless of these advantages,... (Review)
Review
Mineral oil as a barrier can minimize temperature, osmolality, and pH fluctuation of the media in the embryo production system (IVP). Regardless of these advantages, mineral oil quality is varied and may deteriorate during storage or transport conditions. So, it can affect the IVP outcome by absorbing the essentials factors or realizing the toxic components into the media. Although, some methods have already been developed to reduce these side effects, still there is a big concern about the safety and use of mineral oil in the IVP system. In this review, we provided an overview of the advantages and disadvantages of using mineral oil in the IVP system. We also reviewed available methods for its quality control and finally, we introduced some methods for reducing the side effects of mineral oil.
Topics: Animals; Mineral Oil; Temperature
PubMed: 36883153
DOI: 10.22092/ARI.2022.358955.2343 -
Photodermatology, Photoimmunology &... May 2023PUVA phototherapy is indicated for various dermatological conditions. Adverse events due to PUVA phototherapy are seen in a sizable number of patients and can result in... (Review)
Review
PURPOSE
PUVA phototherapy is indicated for various dermatological conditions. Adverse events due to PUVA phototherapy are seen in a sizable number of patients and can result in therapy cessation. This review will focus on PUVA pricks, an adverse event first reported by Tegner in 1979.
METHODS
Articles were retrieved from PubMed starting from January 1979 until February 2021 yielding 1228 unique articles. Articles were included when they described individual patient characteristics, and patients were treated with PUVA therapy.
RESULTS
After screening, 33 patients were extracted from 9 articles, published between 1979 and 2005.
CONCLUSION
PUVA pricks are paroxysmal episodes of burning or prickling pain, akin to peripheral neuropathy of the unmyelinated C-fibers. Increased excitability of TRPV1 and TRPA1 channels while under PUVA therapy might be a contributing factor. Effective topical treatment options for PUVA pricks are capsaicin 8% cream, urea 4%, or petrolatum emollients. Antiepileptics such as phenytoin, clonazepam, and gabapentin are acceptable oral treatment options. A possible role of N-acetylcysteine in the prevention of PUVA pricks is discussed, though further research is required.
Topics: Humans; PUVA Therapy; Emollients; Petrolatum
PubMed: 35906863
DOI: 10.1111/phpp.12824 -
Circulation Aug 2022REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial) reported a 25% relative risk reduction in major adverse cardiovascular events with... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of Randomized Treatment With Icosapent Ethyl and a Mineral Oil Comparator on Interleukin-1β, Interleukin-6, C-Reactive Protein, Oxidized Low-Density Lipoprotein Cholesterol, Homocysteine, Lipoprotein(a), and Lipoprotein-Associated Phospholipase A2: A REDUCE-IT Biomarker Substudy.
BACKGROUND
REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial) reported a 25% relative risk reduction in major adverse cardiovascular events with use of icosapent ethyl compared with pharmaceutical grade mineral oil. The mechanisms underlying this benefit remain uncertain. We explored whether treatment allocation in REDUCE-IT might affect a series of biomarkers in pathways known to associate with atherosclerosis risk.
METHODS
Serum levels of interleukin-1β, interleukin-6, high-sensitivity C-reactive protein, oxidized low-density lipoprotein cholesterol, homocysteine, lipoprotein(a), and lipoprotein-associated phospholipase A2 (Lp-PLA2) were measured at baseline, at 12 months, at 24 months, and at the end-of-study visit among REDUCE-IT participants with triglyceride levels 135 mg/dL and <500 mg/dL who were randomly allocated to treatment with either 4 grams daily of icosapent ethyl or mineral oil used as a comparator.
RESULTS
At baseline, median levels of each biomarker were similar in the 2 treatment groups. The levels of biomarkers associated with atherosclerosis increased over time among those allocated to mineral oil treatment; in this group at 12 months, the median percent increases from baseline were 1.5% for homocysteine, 2.2% for lipoprotein(a), 10.9% for oxidized low-density lipoprotein cholesterol, 16.2% for interleukin-6, 18.5% for lipoprotein-associated phospholipase A2, 21.9% for high-sensitivity C-reactive protein, and 28.9% for interleukin-1β (all values <0.001), with similar changes at 24 months. In the icosapent ethyl group, there were minimal changes in these biomarkers at 12 and 24 months. As such, at study conclusion, between-group treatment differences largely reflected increases in the mineral oil group with median percent differences of 2.4% for lipoprotein(a), 3.0% for homocysteine, 4.2% for oxidized low-density lipoprotein cholesterol, 19.8% for interleukin-6, 26.2% for Lp-PLA2, 38.5% for high-sensitivity C-reactive protein, and 48.7% for interleukin-1β (all values ≤0.007). These data are consistent with previous REDUCE-IT results in which the median percent change for low-density lipoprotein cholesterol at 12 months was -1.2% among those allocated to icosapent ethyl and 10.9% among those allocated to the mineral oil comparator.
CONCLUSIONS
Among participants in REDUCE-IT, allocation to icosapent ethyl had minimal effects on a series of biomarkers associated with atherosclerotic disease, whereas levels increased among those allocated to mineral oil. The effect of these findings on interpretation of the overall risk reductions in clinical events observed within REDUCE-IT is uncertain.
REGISTRATION
URL: https://www.
CLINICALTRIALS
gov; Unique identifier: NCT01492361.
Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Atherosclerosis; Biomarkers; C-Reactive Protein; Cholesterol; Cholesterol, LDL; Double-Blind Method; Eicosapentaenoic Acid; Homocysteine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertriglyceridemia; Interleukin-1beta; Interleukin-6; Lipoprotein(a); Mineral Oil
PubMed: 35762321
DOI: 10.1161/CIRCULATIONAHA.122.059410 -
Turkiye Parazitolojii Dergisi Mar 2021Phthiriasis palpebrarum is a rare eyelid infestation caused by (pubic lice) that is often confused with other causes of blepharoconjunctivitis. In this study, we report...
Phthiriasis palpebrarum is a rare eyelid infestation caused by (pubic lice) that is often confused with other causes of blepharoconjunctivitis. In this study, we report the case of a 49-year-old male patient with phthiriasis palpebrarum who presented with itching and eye irritation in the left eye and had undergone treatment for conjunctivitis in the past month. Biomicroscopic examination revealed a dense population of motile and translucent lice and eggs, more intensely on the upper lid. For treatment, the lice were first cleaned mechanically, eyelashes were cut from the bottom, and eggs and lice were removed from the eye, after which petrolatum jelly (vsaseline) was applied to the lids for 10 days. In the control examination, no lice and eggs were observed.
Topics: Animals; Blepharitis; Eyelashes; Humans; Lice Infestations; Male; Middle Aged; Petrolatum; Phthirus; Treatment Outcome
PubMed: 33685072
DOI: 10.4274/tpd.galenos.2020.6937