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1.
J Drugs Dermatol ; 23(8): 607-611, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39093652

ABSTRACT

BACKGROUND: The combined use of topical calcipotriol/betamethasone dipropionate (Cal/BDP) is commonly used and demonstrated to be effective for the management of psoriasis and is shown to confer local anti-inflammatory and immunoregulatory effects. The use of the two agents in combination is synergistic. Despite the demonstrated efficacy of topically applied combination Cal/BDP, successful management of a chronic, relapsing inflammatory skin disease such as psoriasis in the real-world setting may be hindered if patients do not adhere to the dosing or frequency of application recommendations from their prescriber. Patient preference for and satisfaction with the topical treatment vehicle have been shown to influence adherence. A recent analysis has determined that patients perceived Cal/BDP cream vehicle with PAD technology as having favorable characteristics. This randomized, split-body study was undertaken to further assess patient satisfaction with Cal/BDP cream and Cal/BDP foam formulations. TRIAL DESIGN: This was a split-body, subject-blind study. Study cream was administered in a single application to one side of the scalp and/or body; study foam was applied to the contralateral side. Patient self-administered questionnaires were completed before and after product application after a single site visit. RESULTS: Mean overall Vehicle Preference Measure (VPM) scores were higher for Cal/BDP cream than Cal/BDP foam (P=0.0043). Cal/BDP cream also achieved higher individual scores for ease of application, feeling to the touch, smell, and feeling on the skin (P<0.03). With regards to scalp application, subject assessments show that the cream was significantly more preferred in terms of limiting daily disruption (P=0.0008) Conclusion: Results of this study suggest that patients may prefer Cal/BDP cream over Cal/BDP foam for the management of psoriasis on the body and the scalp. Cal/BDP cream outperformed Cal/BDP foam on several specific measures of satisfaction and overall satisfaction measures. J Drugs Dermatol. 2024;23(8):607-611.  doi:10.36849/JDD.7993.


Subject(s)
Betamethasone , Calcitriol , Dermatologic Agents , Drug Combinations , Patient Preference , Psoriasis , Skin Cream , Humans , Psoriasis/drug therapy , Psoriasis/psychology , Calcitriol/analogs & derivatives , Calcitriol/administration & dosage , Betamethasone/administration & dosage , Betamethasone/analogs & derivatives , Female , Male , Middle Aged , Adult , Dermatologic Agents/administration & dosage , Skin Cream/administration & dosage , Administration, Cutaneous , Single-Blind Method , Severity of Illness Index , Aged , Treatment Outcome , Patient Satisfaction , Surveys and Questionnaires
2.
Neurosci Lett ; 838: 137922, 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39127125

ABSTRACT

OBJECTIVE: Vitamin D deficiency (VDD) is emerging as a predictor of poor prognosis in various neurological conditions, where clinical outcomes are often worse in stroke patients with VDD. This study aimed to provide experimental evidence on whether and how pre-existing VDD would affect survival and neurofunctional outcomes in intracerebral haemorrhage (ICH), and to evaluate whether acute vitamin D (VD) supplementation would improve post-stroke outcomes. METHODS: Experimental ICH models were induced in mice with and without VDD. Haematoma size was measured using T2*-weighted MRI and haemoglobin concentration. Post-ICH mortality, neurofunctional outcomes and the extent of blood-brain barrier (BBB) leakage were assessed to identify their correlations with VD status. Therapeutic benefits of acute VD administration were also evaluated. RESULTS: Mice with VDD exhibited significantly higher acute mortality rates and more severe motor deficits than mice without VDD post-ICH. Marked haematoma expansion and increased Evans blue extravasation were observed in VDD mice, suggesting that VDD was associated outcomes with increased BBB disruption. Acute treatment with a loading dose of VD (calcitriol) significantly improved outcomes in VDD mice. CONCLUSION: This study provides novel insights into the pathophysiological mechanisms at play in ICH concomitant with VDD and a scientific rationale for acute treatment with VD.


Subject(s)
Blood-Brain Barrier , Calcitriol , Cerebral Hemorrhage , Vitamin D Deficiency , Animals , Cerebral Hemorrhage/drug therapy , Vitamin D Deficiency/drug therapy , Vitamin D Deficiency/complications , Calcitriol/pharmacology , Calcitriol/therapeutic use , Calcitriol/administration & dosage , Male , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Mice , Mice, Inbred C57BL
4.
J Dent Res ; 103(9): 908-915, 2024 08.
Article in English | MEDLINE | ID: mdl-39104028

ABSTRACT

There is a strong association between vitamin D levels and periodontal disease based on numerous epidemiological studies. We have previously shown that experimental deficiency of serum vitamin D in mice leads to gingival inflammation and alveolar bone loss. Treatment of cultured oral epithelial cells with the active form of vitamin D, 1,25(OH)2 vitamin D3 (1,25(OH)2D3), inhibits the extracellular growth and intracellular invasion of bacteria associated with periodontal disease. Maintenance of periodontal health may be due in part to the anti-inflammatory activities of vitamin D. Furthermore, this hormone can induce the expression of an antimicrobial peptide in cultured oral epithelial cells. We have shown that oral epithelial cells are capable of converting inactive vitamin D to the active form, suggesting that topical treatment of the oral epithelium with inactive vitamin D could prevent the development of periodontitis. We subjected mice to ligature-induced periodontitis (LIP), followed by daily treatment with inactive vitamin D or 1,25(OH)2D3. Treatment with both forms led to a reduction in ligature-induced bone loss and inflammation. Gingival tissues obtained from vitamin D-treated LIP showed production of specialized proresolving mediators (SPM) of inflammation. To examine the mechanism, we demonstrated that apical treatment of 3-dimensional cultures of primary gingival epithelial cells with vitamin D prevented lipopolysaccharide-induced secretion of proinflammatory cytokines and led to a similar production of SPM. Analysis of the oral microbiome of the mice treated with vitamin D showed significant changes in resident bacteria, which reflects a shift toward health-associated species. Together, our results show that topical treatment of oral tissues with inactive vitamin D can lead to the maintenance of periodontal health through the regulation of a healthy microbiome and the stimulation of resolution of inflammation. This strongly supports the development of a safe and effective vitamin D-based topical treatment or preventive agent for periodontal inflammation and disease.


Subject(s)
Administration, Topical , Alveolar Bone Loss , Disease Models, Animal , Periodontitis , Vitamin D , Animals , Mice , Alveolar Bone Loss/prevention & control , Vitamin D/pharmacology , Vitamin D/administration & dosage , Vitamin D/therapeutic use , Periodontitis/prevention & control , Gingiva/drug effects , Calcitriol/pharmacology , Calcitriol/administration & dosage , Calcitriol/therapeutic use , Mice, Inbred C57BL , Gingivitis/prevention & control
5.
Med J Malaysia ; 79(Suppl 4): 72-76, 2024 08.
Article in English | MEDLINE | ID: mdl-39215419

ABSTRACT

INTRODUCTION: Inflammation caused by diabetes can damage multiple organs, including the lungs. Vitamin D (VD) has been shown to potentially reduce inflammation and boost the immune system. VD might play a role in diabetes' inflammatory response. This study aims to elucidate the evidence regarding the lung as the target organ for DM and the possible role of VD in preventing pulmonary damage progression in the diabetes rat model. MATERIAL AND METHODS: Thirty Sprague Dawley rats (3-monthold, 200 to 300 gm) were randomly divided into six groups, namely control (C), 4 weeks diabetes mellitus (DM1), 8 weeks DM (DM2) and three DM1 groups (VD1, VD2, and VD3) who received Vitamin D doses of 0.125, 0.25 and 0.50 µg/kg BW, respectively. After 4 weeks, daily VD was administered intraperitoneally for 30 days. Lung tissues were taken for IL- 6, MCP-1, NFKB and CD68 mRNA expression analysis and paraffin embedding. Immunohistochemical staining against CD68 and MCP-1 was conducted. Data were analysed using one-way ANOVA. p < 0.05 was considered statistically significant. RESULTS: DM2 group represented significantly higher IL6, MCP1, NFKB and CD68 mRNA expression than Control group (p < 0.05). Meanwhile, VD2 and VD3 groups revealed significantly lower mRNA expression of IL-6, MCP1, NFKB and CD68 than DM2 (p < 0.05). Immunostaining revealed the spreading of MCP1 protein expression in lung tissue along with macrophage infiltration in the DM2 group, which was reduced in the VD2 and the VD3 groups. CONCLUSION: VD shows a protective effect on diabetesinduced lung damage by regulating inflammation factors.


Subject(s)
Calcitriol , Diabetes Mellitus, Experimental , Rats, Sprague-Dawley , Animals , Calcitriol/pharmacology , Calcitriol/administration & dosage , Rats , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/complications , Lung/drug effects , Lung/metabolism , Lung/pathology , Male , Inflammation/drug therapy , Chemokine CCL2/metabolism , Disease Models, Animal , Interleukin-6/metabolism
6.
Drug Des Devel Ther ; 18: 2593-2608, 2024.
Article in English | MEDLINE | ID: mdl-38947224

ABSTRACT

Objective: To quantitatively assess all dosage forms of three active vitamin D and its analogs, namely, calcitriol, alfacalcidol, and eldecalcitol, to provide a basis for the selection of active vitamin D and its analogs in hospitals. Methods: In this study, three active vitamin D and its analogs were evaluated by quantitative scoring in five dimensions, including pharmaceutical properties (28 points), efficacy (27 points), safety (25 points), economy (10 points), and other attributes (10 points). Results: The final scores of quantitative assessment for the selection of alfacalcidol soft capsules, calcitriol soft capsules I, calcitriol soft capsules II, alfacalcidol tablets, alfacalcidol capsules, alfacalcidol oral drops, calcitriol injection, and eldecalcitol soft capsules were 73.17, 72.06, 71.52, 71.29, 69.62, 68.86, 65.60, 64.05 points. Conclusion: Based on the scoring results, alfacalcidol soft capsules, calcitriol soft capsules I, calcitriol soft capsules II, alfacalcidol tablets can be entered into the medication list of medical institutions as strongly recommended drugs. This study offers guidance on selecting and using active vitamin D and its analogs in hospitals, with consideration for the patient's needs.


Subject(s)
Hydroxycholecalciferols , Osteoporosis , Vitamin D , Humans , Osteoporosis/drug therapy , Vitamin D/administration & dosage , Vitamin D/analogs & derivatives , Hydroxycholecalciferols/administration & dosage , Hydroxycholecalciferols/therapeutic use , Technology Assessment, Biomedical , Bone Density Conservation Agents/administration & dosage , China , Calcitriol/analogs & derivatives , Calcitriol/administration & dosage , Capsules
7.
Biomed Pharmacother ; 177: 116926, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38906016

ABSTRACT

Obesity aggravates ferroptosis, and vitamin D (VD) may inhibit ferroptosis. We hypothesized that weight reduction and/or calcitriol administration have benefits against the sepsis-induced liver redox imbalance and ferroptosis in obese mice. Mice were fed a high-fat diet for 11 weeks, then half of the mice continued to consume the diet, while the other half were transferred to a low-energy diet for 5 weeks. After feeding the respective diets for 16 weeks, sepsis was induced by cecal ligation and puncture (CLP). Septic mice were divided into four experimental groups: OS group, obese mice injected with saline; OD group, obese mice with calcitriol; WS group, weight-reduction mice with saline; and WD group, weight-reduction mice with calcitriol. Mice in the respective groups were euthanized at 12 or 24 h after CLP. Results showed that the OS group had the highest inflammatory mediators and lipid peroxide levels in the liver. Calcitriol treatment reduced iron content, enhanced the reduced glutathione/oxidized glutathione ratio, upregulated nuclear factor erythroid 2-related factor 2, ferroptosis-suppressing protein 1, and solute carrier family 7 member 11 expression levels. Also, mitochondrion-associated nicotinamide adenine dinucleotide phosphate oxidase 1, peroxisome proliferator-activated receptor-γ coactivator 1, hypoxia-inducible factor-1α, and heme oxidase-1 expression levels increased in the late phase of sepsis. These results were not noted in the WS group. These findings suggest that calcitriol treatment elicits a more-balanced glutathione redox status, alleviates liver ferroptosis, and enhances mitochondrial biogenesis-associated gene expressions. Weight reduction alone had minimal influences on liver ferroptosis and mitochondrial biogenesis in obese mice with sepsis.


Subject(s)
Calcitriol , Diet, High-Fat , Ferroptosis , Liver , Mice, Inbred C57BL , Obesity , Oxidation-Reduction , Sepsis , Animals , Sepsis/complications , Sepsis/drug therapy , Sepsis/metabolism , Diet, High-Fat/adverse effects , Obesity/metabolism , Obesity/complications , Obesity/drug therapy , Liver/metabolism , Liver/drug effects , Liver/pathology , Oxidation-Reduction/drug effects , Ferroptosis/drug effects , Male , Mice , Calcitriol/pharmacology , Calcitriol/administration & dosage , Mice, Obese
8.
Mov Disord ; 39(7): 1099-1108, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38696306

ABSTRACT

BACKGROUND: Calcitriol, the active form of vitamin D (also known as 1,25-dihydroxycholecalciferol), improves the phenotype and increases frataxin levels in cell models of Friedreich ataxia (FRDA). OBJECTIVES: Based on these results, we aimed measuring the effects of a calcitriol dose of 0.25 mcg/24h in the neurological function and frataxin levels when administered to FRDA patients for a year. METHODS: 20 FRDA patients where recluted and 15 patients completed the treatment for a year. Evaluations of neurological function changes (SARA scale, 9-HPT, 8-MWT, PATA test) and quality of life (Barthel Scale and Short Form (36) Health Survey [SF-36] quality of life questionnaire) were performed. Frataxin amounts were measured in isolated platelets obtained from these FRDA patients, from heterozygous FRDA carriers (relatives of the FA patients) and from non-heterozygous sex and age matched controls. RESULTS: Although the patients did not experience any observable neurological improvement, there was a statistically significant increase in frataxin levels from initial values, 5.5 to 7.0 pg/µg after 12 months. Differences in frataxin levels referred to total protein levels were observed among sex- and age-matched controls (18.1 pg/µg), relative controls (10.1 pg/µg), and FRDA patients (5.7 pg/µg). The treatment was well tolerated by most patients, and only some of them experienced minor adverse effects at the beginning of the trial. CONCLUSIONS: Calcitriol dosage used (0.25 mcg/24 h) is safe for FRDA patients, and it increases frataxin levels. We cannot rule out that higher doses administered longer could yield neurological benefits. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Subject(s)
Calcitriol , Frataxin , Friedreich Ataxia , Iron-Binding Proteins , Humans , Friedreich Ataxia/drug therapy , Male , Female , Calcitriol/pharmacology , Calcitriol/administration & dosage , Adult , Middle Aged , Young Adult , Quality of Life , Adolescent , Treatment Outcome
9.
J Dermatolog Treat ; 35(1): 2357618, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38797809

ABSTRACT

BACKGROUND: Psoriasis significantly impacts patients' quality of life (QoL). Dissatisfaction and non-adherence are major barriers associated with topical treatments. A cream based on the polyaphron dispersion (PAD) Technology containing a fixed-dose of calcipotriol (CAL) and betamethasone dipropionate (BDP) was designed for a patient-friendly psoriasis management. The CAL/BDP PAD-cream demonstrated efficacy, convenience, and safety/tolerability in clinical trials. OBJECTIVES: This research assesses the real-world use, perception, satisfaction, and adherence of CAL/BDP PAD-cream among plaque psoriasis patients. METHODS: Between September-November 2023, psoriasis patients from Spain and Germany using or having used CAL/BDP PAD-cream for >2 weeks were recruited via Wefight network to complete a 30-questions online survey. Anonymized results were pooled for descriptive statistical analysis. RESULTS: The survey was completed by 129 patients (mean age: 43 years; 66% females; mean psoriasis duration: 12 years). Most patients (93%) were satisfied with CAL/BDP PAD-cream. The 66% reported high adherence (visual analogue scale 80-100) and 91% preferred CAL/BDP PAD-cream to their previous topical(s). Patients highlighted its ease/convenience of application, tolerability, and lack of itching/burning. CONCLUSIONS: Psoriasis patients treated with CAL/BDP PAD-cream in a real-world setting show high satisfaction, good adherence, and a positive perception of the product, suggesting that favorable outcomes observed in clinical trials translate to real clinical practice.


Subject(s)
Betamethasone , Calcitriol , Dermatologic Agents , Medication Adherence , Patient Satisfaction , Psoriasis , Humans , Psoriasis/drug therapy , Calcitriol/analogs & derivatives , Calcitriol/administration & dosage , Female , Betamethasone/analogs & derivatives , Betamethasone/administration & dosage , Betamethasone/therapeutic use , Male , Adult , Medication Adherence/statistics & numerical data , Germany , Cross-Sectional Studies , Spain , Middle Aged , Dermatologic Agents/administration & dosage , Dermatologic Agents/therapeutic use , Quality of Life , Skin Cream/administration & dosage , Surveys and Questionnaires , Drug Combinations , Administration, Cutaneous
10.
Mol Pharm ; 21(6): 2813-2827, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38752564

ABSTRACT

Psoriasis, affecting 2-3% of the global population, is a chronic inflammatory skin condition without a definitive cure. Current treatments focus on managing symptoms. Recognizing the need for innovative drug delivery methods to enhance patient adherence, this study explores a new approach using calcipotriol monohydrate (CPM), a primary topical treatment for psoriasis. Despite its effectiveness, CPM's therapeutic potential is often limited by factors like the greasiness of topical applications, poor skin permeability, low skin retention, and lack of controlled delivery. To overcome these challenges, the study introduces CPM in the form of nanosuspensions (NSs), characterized by an average particle size of 211 ± 2 nm. These CPM NSs are then incorporated into a trilayer dissolving microneedle patch (MAP) made from poly(vinylpyrrolidone) and w poly(vinyl alcohol) as needle arrays and prefrom 3D printed polylactic acid backing layer. This MAP features rapidly dissolving tips and exhibits good mechanical properties and insertion capability with delivery efficiency compared to the conventional Daivonex ointment. The effectiveness of this novel MAP was tested on Sprague-Dawley rats with imiquimod-induced psoriasis, demonstrating efficacy comparable to the marketed ointment. This innovative trilayer dissolving MAP represents a promising new local delivery system for calcipotriol, potentially revolutionizing psoriasis treatment by enhancing drug delivery and patient compliance.


Subject(s)
Administration, Cutaneous , Calcitriol , Drug Delivery Systems , Needles , Psoriasis , Rats, Sprague-Dawley , Psoriasis/drug therapy , Animals , Calcitriol/analogs & derivatives , Calcitriol/administration & dosage , Rats , Drug Delivery Systems/methods , Skin Absorption/drug effects , Skin/metabolism , Skin/drug effects , Skin/pathology , Particle Size , Male , Nanoparticles/chemistry , Imiquimod/administration & dosage , Suspensions , Dermatologic Agents/administration & dosage , Dermatologic Agents/pharmacokinetics , Transdermal Patch
11.
Int J Pharm ; 659: 124237, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38762167

ABSTRACT

Intranasal administration is an efficient strategy for bypassing the BBB, favoring drug accumulation in the brain, and improving its efficiency. Lipid nanocapsules (LNC) are suitable nanocarriers for the delivery of lipophilic drugs via this route and can be used to encapsulate lipophilic molecules such as retinoic acid (RA) and calcitriol (Cal). As the hallmarks of multiple sclerosis (MS) are neuroinflammation and oligodendrocyte loss, our hypothesis was that by combining two molecules known for their pro-differentiating properties, encapsulated in LNC, and delivered by intranasal administration, we would stimulate oligodendrocyte progenitor cells (OPC) differentiation into oligodendrocytes and provide a new pro-remyelinating therapy. LNC loaded with RA (LNC-RA) and Cal (LNC-Cal) were stable for at least 8 weeks. The combination of RA and Cal was more efficient than the molecules alone, encapsulated or not, on OPC differentiation in vitro and decreased microglia cell activation in a dose-dependent manner. After the combined intranasal administration of LNC-RA and LNC-Cal in a mouse cuprizone model of demyelination, increased MBP staining was observed in the corpus callosum. In conclusion, intranasal delivery of lipophilic drugs encapsulated in LNC is a promising strategy for myelinating therapies.


Subject(s)
Administration, Intranasal , Calcitriol , Cell Differentiation , Nanocapsules , Oligodendrocyte Precursor Cells , Tretinoin , Animals , Tretinoin/administration & dosage , Tretinoin/pharmacology , Cell Differentiation/drug effects , Calcitriol/administration & dosage , Calcitriol/pharmacology , Oligodendrocyte Precursor Cells/drug effects , Mice , Mice, Inbred C57BL , Lipids/chemistry , Cells, Cultured , Male
12.
Int J Pharm ; 659: 124278, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38806095

ABSTRACT

The aim of this work was the development of a film-forming formulation (FFF) for the topical treatment of psoriasis that shows an increased substantivity compared to conventional semi-solid dosage forms. The developed formulation is an oleogel. It is based on a combination of castor oil and medium chain triglycerides, and the oil-soluble film former MP-30 (Croda GmbH, Nettetal, Germany), a polyamide that upon mixing with a polar oil entraps the oil und thus substantially increases the viscosity of the formulation up to a semisolid state. Betamethasone dipropionate (BDP) and calcipotriole (CA) were used as active pharmaceutical ingredients (APIs). Oleogels of different compositions were evaluated regarding substantivity, rheological properties, ex-vivo penetration into the skin and ex-vivo permeation through the skin. Marketed products were used as controls. It was found that the amount of betamethasone dipropionate penetrating and permeating into and through the skin from the film-forming formulation is at an intermediate value compared to the marketed products. The substantivity of the developed formulation is described by an amount of 57.7 % formulation that remains on the skin surface and is thus significantly higher compared to the marketed products. In the film forming formulation, the proportion of API penetrating the skin remains the same when the skin repetitively brought in contact with a piece of textile during the penetration experiment. In contrast with the in-market formulations tested, this proportion was reduced by up to 97 %. As a result, the developed formulations can lead to an increased patient compliance.


Subject(s)
Betamethasone , Organic Chemicals , Psoriasis , Skin Absorption , Skin , Psoriasis/drug therapy , Betamethasone/administration & dosage , Betamethasone/analogs & derivatives , Betamethasone/chemistry , Betamethasone/pharmacokinetics , Animals , Organic Chemicals/chemistry , Organic Chemicals/administration & dosage , Skin Absorption/drug effects , Skin/metabolism , Dermatologic Agents/administration & dosage , Dermatologic Agents/chemistry , Dermatologic Agents/pharmacokinetics , Calcitriol/analogs & derivatives , Calcitriol/administration & dosage , Calcitriol/chemistry , Triglycerides/chemistry , Administration, Cutaneous , Castor Oil/chemistry , Swine , Viscosity , Chemistry, Pharmaceutical/methods , Rheology
13.
J Cutan Med Surg ; 28(4): 375-380, 2024.
Article in English | MEDLINE | ID: mdl-38783539

ABSTRACT

BACKGROUND/OBJECTIVES: Actinic keratoses (AK) are premalignant skin lesions caused by chronic sun exposure, topically managed by 5-fluorouracil (5-FU), diclofenac 3% gel, and imiquimod. Despite their effectiveness, long treatment duration and severe adverse local skin reactions have limited patient concordance. Calcipotriol has recently been used as a combination agent for existing topical AK treatments. A systematic review was performed to determine the clinical efficacy of 5-FU and calcipotriol for the treatment of AK, Bowen's disease, and squamous cell carcinoma (SCC). METHODS: A systematic literature search was conducted on Medline, Embase, and Cochrane Library. Among the 84 records screened, 12 were retrieved for full-text review and 8 were included in the final analysis. RESULTS: Among the 8 studies, there were 214 control patients and 288 patients who received the intervention. The combination 5% 5-FU with calcipotriol resulted in a significant reduction in the number of AKs on the face, scalp, right upper extremity, and left upper extremity for all sites at 8 weeks (P < .0001). No significant difference in SCC incidence was observed at 1 or 2 years, but there was a significant reduction observed at 3 years for SCC on face and scalp. No study assessed the combination for Bowen's disease. CONCLUSIONS: Combination 5% 5-FU with calcipotriol is an effective treatment for Aks; however, future trials may consider longer treatment and follow-up periods for the treatment and prevention of AK, SCC in situ, and SCC.


Subject(s)
Bowen's Disease , Calcitriol , Carcinoma, Squamous Cell , Fluorouracil , Keratosis, Actinic , Skin Neoplasms , Humans , Fluorouracil/administration & dosage , Fluorouracil/therapeutic use , Calcitriol/analogs & derivatives , Calcitriol/administration & dosage , Calcitriol/therapeutic use , Bowen's Disease/drug therapy , Keratosis, Actinic/drug therapy , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Dermatologic Agents/administration & dosage , Dermatologic Agents/therapeutic use , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/therapeutic use , Drug Therapy, Combination , Administration, Cutaneous
14.
J Dermatol ; 51(7): 1010-1016, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38716641

ABSTRACT

Small plaque psoriasis is the typical form of chronic plaque psoriasis affecting adults in South Korea. The effectiveness of calcipotriol/betamethasone dipropionate (Cal/BD) aerosol foam for large and small psoriasis plaques has not previously been examined. We performed a post hoc analysis of a recent, 4-week observational study of Cal/BD aerosol foam use in routine clinical practice in South Korea. Investigator Global Assessment response ([IGA] 0/1 at week 4), Patient Global Assessment response ([PaGA] 0/1 at week 4), change in Psoriasis Area and Severity Index (PASI), changes in psoriasis symptom scores, change in the Dermatology Life Quality Index (DLQI), and the proportion of patients achieving DLQI ≤5 were analyzed for patients with small (≤5 cm; n = 131) or large (>5 cm; n = 35) baseline plaque size. IGA response rates were similar for patients with small and large plaques (59.5% and 51.4% respectively). Similarly, there was no significant difference between the small and large groups in mean change in PASI (-2.20 vs -3.34), the proportions of patients with DLQI ≤5 (62.3% vs 54.3%) or PaGA 0/1 (29.2% vs 40.0%). Mean improvements in DLQI (-4.04 vs -6.20) and in psoriasis symptoms including itching (-1.50 vs -2.83), sleep loss (-0.67 vs -1.89), dryness (-1.57 vs -2.97), scaling (-1.21 vs -3.57), and redness (-1.17 vs -3.11) were greater in patients with large plaques than those with small plaques. Itching and DLQI differences were not statistically significant after adjustment for baseline characteristics. Stratification by body surface area affected eliminated statistically significant differences between the groups for most outcomes. In conclusion, this analysis suggests that Cal/BD aerosol foam is an effective, well-accepted treatment for adult patients with the small plaques typical of chronic plaque psoriasis in South Korea, as well as for those with large plaques.


Subject(s)
Aerosols , Betamethasone , Calcitriol , Dermatologic Agents , Psoriasis , Quality of Life , Severity of Illness Index , Humans , Psoriasis/drug therapy , Psoriasis/diagnosis , Psoriasis/pathology , Calcitriol/analogs & derivatives , Calcitriol/administration & dosage , Male , Betamethasone/administration & dosage , Betamethasone/analogs & derivatives , Female , Republic of Korea , Middle Aged , Adult , Treatment Outcome , Dermatologic Agents/administration & dosage , Drug Combinations , Aged
15.
Article in English | MEDLINE | ID: mdl-38566376

ABSTRACT

OBJECTIVES: Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease affecting the central nervous system. Immune cell subsets, notably T helper (Th) 17 and Th1, exert important roles in MS pathogenesis. Whereas, Treg cells modulate the disease process. Calcitriol, the active form of vitamin D, and curcumin, a bioactive compound derived from turmeric, play immunomodulatory effects relevant to autoimmune disorders, including MS. The objective of this study is to investigate the effects of calcitriol and Curcumin on Peripheral blood mononuclear cells (PBMCs) of individuals with MS. METHODS: PBMCs from twenty MS patients were isolated, cultured, and exposed to 0.004 µg/mL of calcitriol and 10 µg/mL of curcumin. The cells underwent treatment with singular or combined doses of these components to assess potential cumulative or synergistic immunomodulatory effects. Following treatment, the expression levels of genes and the cellular population of Treg, Th1 and Th17 were evaluated using Real-time PCR and flow cytometry. RESULTS: Treatment with curcumin and calcitriol led to a significant reduction in the expression levels of inflammatory cytokines and transcription factors related to Th1 and Th17 cells, including IFN-γ, T-bet, IL-17, and RORC. Furthermore, the frequency of these cells decreased following treatment. Additionally, curcumin and calcitriol treatment resulted in a significant upregulation of the FOXP3 gene expression and an increase in the frequency of Treg cells. CONCLUSION: This study demonstrates that curcumin and calcitriol can effectively modulate the inflammatory processes intrinsic to MS by mitigating the expression of inflammatory cytokines by Th1 and Th17 cells while concurrently enhancing the regulatory role of Treg cells. Moreover, the combined treatment of curcumin and calcitriol did not yield superior outcomes compared to single-dosing strategies.


Subject(s)
Calcitriol , Curcumin , Leukocytes, Mononuclear , Multiple Sclerosis , Humans , Curcumin/pharmacology , Curcumin/administration & dosage , Calcitriol/pharmacology , Calcitriol/administration & dosage , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/immunology , Multiple Sclerosis/drug therapy , Multiple Sclerosis/immunology , Female , Adult , Male , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology , Cells, Cultured , Cytokines/metabolism , Immunomodulating Agents/pharmacology , Immunomodulating Agents/therapeutic use , Th1 Cells/drug effects , Th1 Cells/immunology , Th17 Cells/drug effects , Th17 Cells/immunology , Middle Aged , Immunologic Factors/pharmacology , Immunologic Factors/therapeutic use , Forkhead Transcription Factors
16.
J Ethnopharmacol ; 330: 118166, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-38621466

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is a chronic inflammatory skin disease. Vitamin D analogues are the first-line topical agents for the long-term management of psoriasis. Chinese herbal medicine (CHM) bath therapy is commonly employed for psoriasis. However, the effects and safety of CHM bath therapy for psoriasis vulgaris, using topical calcipotriol as the comparator, remain inconclusive. Furthermore, the combination of herbs, a distinctive feature of CHM, is essential for its therapeutic effects due to the individual and synergistic properties of the herbs involved. AIM OF THE STUDY: The review was conducted to evaluate the effectiveness and safety of CHM bath therapy for psoriasis vulgaris, using calcipotriol as the comparator. Potential herbs and herb combinations of CHM bath therapy were also explored for further drug discovery. MATERIALS AND METHODS: Nine databases were searched from inception until March 05, 2024. Randomised controlled trials (RCTs) investigating CHM bath therapy, using calcipotriol as the comparator, were included. Statistical analyses were performed using RevMan 5.4, Stata 12.0 and SPSS Clementine 12.0 software. The evidence certainty for outcomes was assessed using the approach proposed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group. Moreover, association rule analysis on herbs identified in the systematic review was conducted to explore the potential herbs and herb combinations. RESULTS: A total of 17 RCTs involving 1,379 participants were included in this systematic review. The findings of this review revealed that: 1) CHM bath therapy produced comparable effects to calcipotriol in reducing Psoriasis Area and Severity Index (PASI), Psoriasis Scalp Severity Index (PSSI), and itch visual analogue scale (VAS) at the end of the treatment phase; as well as exhibited a superior long-term effect than calcipotriol through decreasing relapse rates at the end of the follow-up phase; 2) CHM bath therapy showed an additional benefit when combined with calcipotriol in managing psoriasis vulgaris at the end of the treatment phase, in terms of PASI, PSSI, itch VAS, IL-17, IL-23, CD3+ and CD4+ T cells. The certainty of the evidence was rated as 'very low', 'low' or 'moderate' based on the GRADE assessment, considering some concerns or high risk of bias of included studies, substantial heterogeneity, and existing publication bias of some outcomes. Additionally, the proportions of participants reporting adverse events were similar in both groups. Association rule analysis of all included herbs identified 23 herb combinations including Prunus persica (L.) Batsch and Carthamus tinctorius L., as well as 11 frequently used herbs, such as Kochia scoparia (L.) Schrad., Dictamnus dasycarpus Turcz. And Sophora flavescens Ait. CONCLUSIONS: The effects of CHM bath therapy were comparable with those of topical calcipotriol but demonstrated a longer-lasting effect. Combining CHM bath therapy with calcipotriol also provided an additional benefit for adult psoriasis vulgaris. However, the certainty of the evidence was downgraded due to the methodological limitations of included studies. To confirm the findings of this review, future investigations should involve double-blinded, placebo-controlled RCTs. Importantly, it appears worthwhile to consider further research for drug development utilising the identified herbs or herb combinations.


Subject(s)
Calcitriol , Dermatologic Agents , Drugs, Chinese Herbal , Psoriasis , Humans , Baths , Calcitriol/analogs & derivatives , Calcitriol/administration & dosage , Calcitriol/therapeutic use , Dermatologic Agents/administration & dosage , Dermatologic Agents/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/administration & dosage , Medicine, Chinese Traditional/methods , Psoriasis/drug therapy , Randomized Controlled Trials as Topic , Treatment Outcome
17.
Immunol Cell Biol ; 102(5): 353-357, 2024.
Article in English | MEDLINE | ID: mdl-38216149

ABSTRACT

Immunology research holds significant potential for enhanced inclusivity at the beginning of the science literacy journey, but persistent challenges stem from limited awareness that improvement is needed in this field. At the 2023 Monash Sensory Science Exhibition, we had the opportunity to present several tactile posters, using simple materials, for visually impaired participants to showcase our research on the pathogenesis of rheumatoid arthritis as a result of immune tolerance breakdown and liposome-based tolerogenic immunotherapy. The posters stimulated lively discussions about autoimmune arthritic diseases and our research. With consideration of the diversity of the participants, the efforts of scientists in promoting science literacy for the community can promote a more inclusive environment and engage and inspire a broader audience.


Subject(s)
Arthritis, Rheumatoid , Calcitriol , Immune Tolerance , Immunotherapy , Liposomes , Animals , Humans , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/therapy , Autoantigens/immunology , Calcitriol/administration & dosage , Immunotherapy/methods , Peptides/administration & dosage , Peptides/immunology
18.
J Bras Nefrol ; 45(1): 95-101, 2023.
Article in English, Portuguese | MEDLINE | ID: mdl-35980102

ABSTRACT

INTRODUCTION: Hyperparathyroidism (SHPT) secondary to chronic kidney disease (CKD) is characterized by high levels of parathyroid hormone (PTH), hyperplasia of the parathyroid glands and cardiovascular disease. Selective and non-selective and selective vitamin D-receptor activators, calcimimetics, are available in the Brazilian market to reduce PTH levels. OBJECTIVES: To develop a cost-effectiveness (C/E) and budgetary impact (BI) analysis of intravenous paricalcitol vs. oral calcitriol for patients on dialysis with SHPT, from the perspective of the Brazilian Public Health Care System (SUS). METHODOLOGY: We built a decision-tree model to analyze C/E, which considered the outcome of avoided death and a time horizon of 1 year. As for the BI analysis, two scenarios were considered, one of demand and one of epidemiological approach, based on data from the Brazilian Society of Nephrology. RESULTS: The analysis showed that the C/E ratio was R$ 1,213.68 per year, and an incremental effectiveness of 0.032, referring to avoided death. The incremental C/E ratio was R$37,927.50 per death averted by paricalcitol. It was estimated that the incremental BI with the expansion of paricalcitol use will be between R$1,600,202.28 and R$4,128,565.65 in the first year, considering the main and epidemiological scenarios. At the end of 5 years after the expansion of its use, an incremental BI was estimated between R$ 48,596,855.50 and R$ 62,90,555.73. CONCLUSION: Intravenous paricalcitol has superior efficacy and similar safety to oral calcitriol, reducing the overall mortality of dialysis patients, although it implies a higher cost.


Subject(s)
Calcitriol , Ergocalciferols , Hyperparathyroidism, Secondary , Renal Insufficiency, Chronic , Humans , Calcitriol/administration & dosage , Calcitriol/therapeutic use , Cost-Benefit Analysis , Cost-Effectiveness Analysis , Hyperparathyroidism, Secondary/drug therapy , Hyperparathyroidism, Secondary/etiology , Parathyroid Hormone , Renal Dialysis , Renal Insufficiency, Chronic/complications , Ergocalciferols/administration & dosage , Ergocalciferols/therapeutic use
19.
Brain Res Bull ; 181: 21-29, 2022 04.
Article in English | MEDLINE | ID: mdl-35065185

ABSTRACT

Chemotherapy-induced cognitive impairment such as memory impairment and concentration problems are now extensively recognized as side effects of chemotherapy. These problems reduce the quality of life in patients. Therefore, the present study aims to examine the effects of calcitriol supplementation (100 ng/kg /day for five weeks) on cognitive impairment, behavioral deficits, and hippocampal brain-derived neurotrophic factor (BDNF) changes following cisplatin treatment (5 mg/kg/ once a week for five weeks). We also determined the impact of cisplatin and calcitriol administration on reaction time against the thermal stimulus and muscle strength. Our findings showed that cisplatin administration resulted in a significant increase in anxiety-like behaviors. Treatment of rats with cisplatin also impaired performance in the passive avoidance and novel object recognition tasks which are indicating cognitive deficits. Co-administration of calcitriol prevented the cisplatin-induced behavioral and cognitive impairments. Cisplatin exposure also resulted in enhanced reaction time to the thermal stimulus and decreased muscle ability. Besides, hippocampal BDNF levels were reduced in cisplatin-treated rats; however, calcitriol alleviated these effects of cisplatin and up-regulated BDNF mRNA in the hippocampus. In addition, calcitriol alone indicated a significant change in BDNF level compared to the control group. We conclude that increased hippocampal BDNF mediates the beneficial effects of calcitriol against neurotoxicity in cisplatin-exposed rats. However, further studies are required to explore the other mechanisms that mediate the beneficial effect of calcitriol.


Subject(s)
Antineoplastic Agents/adverse effects , Behavioral Symptoms/drug therapy , Brain-Derived Neurotrophic Factor/drug effects , Calcitriol/pharmacology , Cisplatin/adverse effects , Cognitive Dysfunction/drug therapy , Neurotoxicity Syndromes/drug therapy , Animals , Behavior, Animal/drug effects , Behavioral Symptoms/chemically induced , Behavioral Symptoms/metabolism , Calcitriol/administration & dosage , Calcium-Regulating Hormones and Agents , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/metabolism , Dietary Supplements , Disease Models, Animal , Male , Neurotoxicity Syndromes/metabolism , Rats , Up-Regulation
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