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1.
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
2.
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
3.
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
4.
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 , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/therapy , Humans , Immunotherapy/methods , Calcitriol/administration & dosage , Peptides/administration & dosage , Peptides/immunology , Animals , Autoantigens/immunology
5.
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
6.
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
8.
Eur J Dermatol ; 31(5): 638-644, 2021 Oct 01.
Article in English | MEDLINE | ID: mdl-34789450

ABSTRACT

To enhance the efficacy of photodynamic therapy (PDT) for actinic keratosis (AKs), physical and chemical pre-treatments, such as calcipotriol (CAL) have been suggested. To compare the long-term 12-month efficacy and safety between methylaminolevulinate (MAL)-PDT and prior application of topical CAL versus conventional MAL-PDT for AKs of the scalp. Twenty patients with multiple AKs on the scalp were randomized to receive conventional PDT on one side of the scalp and CAL-assisted PDT, in which CAL was applied daily for 15 days beforehand, on the other side. Patients were evaluated for AK clearance at three, six and 12 months thereafter. All 20 patients completed the study. At three months, overall AK clearance was 92.07% and 82.04% for CAL-PDT and conventional PDT, respectively (p < 0.001). Similar results were found at six and 12 months: 92.07% and 81.69% (p < 0.001), and 90.69% and 77.46% (p < 0.001) for CAL-PDT and conventional PDT, respectively. Grade I AKs showed a similar response rate for both sides (p = 0.055) at three months and significant differences were obtained at six (p = 0.001) and 12 months (p < 0.001) for CAL-PDT and conventional PDT. Grade II AKs showed greater improvement on the CAL-PDT side (89.55% vs 62.90%) (p < 0.001) at three months. No difference was found at six and 12 months. CAL-PDT proved to be safe and more effective than conventional PDT for the treatment of AKs on the scalp after 12 months. CAL pre-treatment may have enhanced the efficacy of PDT for AK treatment, however, larger trials are needed to corroborate our findings.


Subject(s)
Aminolevulinic Acid/analogs & derivatives , Calcitriol/analogs & derivatives , Dermatologic Agents/administration & dosage , Keratosis, Actinic/drug therapy , Photochemotherapy/methods , Photosensitizing Agents/administration & dosage , Scalp Dermatoses/drug therapy , Aged , Aged, 80 and over , Aminolevulinic Acid/administration & dosage , Aminolevulinic Acid/adverse effects , Calcitriol/administration & dosage , Calcitriol/adverse effects , Dermatologic Agents/adverse effects , Follow-Up Studies , Humans , Male , Middle Aged , Photosensitizing Agents/adverse effects , Prospective Studies
9.
Iran Biomed J ; 25(6): 417-25, 2021 11 01.
Article in English | MEDLINE | ID: mdl-34641645

ABSTRACT

Background: Hyperuricemia induces nephropathy through the mediation of oxidative stress, tubular injury, inflammation, and fibrosis. The high uric acid level is associated with the reduction of vitamin D levels. However, the reno-protective effects of this vitamin in hyperuricemia condition remain unknown. This study aimed to elucidate calcitriol treatment in a uric acid-induced hyperuricemia mice model. Methods: : Uric acid (125 mg/kg body weight [BW]) was administered intraperitoneally for 7 (UA7) and 14 (UA14) days. Calcitriol (0.5 g/kg BW) was intraperitoneally injected for the following seven days, after 14 days of uric acid induction (UA14VD7 group). The control group received NaCl 0.9%, by the same route. Serum creatinine was measured using calorimetric method, and uric acid levels were assessed using enzymatic calorimetric assay. Tubular injury and fibrosis were assessed using PAS and Sirius red staining. RT-PCR and real-time reverse transcription PCR were carried out for the analyses of SOD-1, Collagen-1, and TGF-1 mRNA expression in the kidney. Immunostaining of super oxide dismutase type 1 (SOD-1) was performed to detect its expression in the kidney. Results: Uric acid and creatinine levels markedly increased in UA14 groups, followed by an exacerbation of tubular injury. RT-PCR revealed the upregulation of Collagen-1 and TGF-1, along with the downregulation of SOD-1. Calcitriol treatment attenuated the injury with reducing uric acid and creatinine levels, as well as tubular injury. This was associated with lower Collagen-1 and TGF-1 mRNA expression compared to the UA7 and UA14 groups. SOD-1 was upregulated in epithelial cells in the UA14VD7 group. Conclusion: Calcitriol treatment after uric acid induction may attenuate kidney injury through upregulation of SOD-1 and downregulation of Collagen-1 and TGF-1 gene expression.


Subject(s)
Calcitriol/pharmacology , Fibrosis/prevention & control , Hyperuricemia/prevention & control , Superoxide Dismutase-1/metabolism , Up-Regulation , Uric Acid/adverse effects , Vitamins/pharmacology , Animals , Calcitriol/administration & dosage , Hyperuricemia/chemically induced , Mice , Vitamins/administration & dosage
10.
J Bone Miner Res ; 36(12): 2361-2370, 2021 12.
Article in English | MEDLINE | ID: mdl-34622481

ABSTRACT

Fractures and vascular calcifications (VCs) are common in patients with chronic kidney disease (CKD). They are related to abnormalities in vitamin D metabolism, calcium, phosphorus, parathyroid hormone, and fibroblast growth factor 23 (FGF23)/Klotho that occur with CKD. Impaired vitamin D metabolism and abnormal levels of calcium, phosphate, parathyroid hormone (PTH), and FGF23/Klotho drive bone and vascular changes in CKD. It is unclear if oral calcitriol safely mitigates fracture risk without increasing the burden of calcifications. Therefore, we investigated whether treatment with calcitriol affected the prevalence of fractures and VC progression in hemodialysis (HD) patients. This report is a secondary analysis of the Vitamin K Italian (VIKI) study, a cross-sectional study involving 387 HD patients. We assessed vitamin 25(OH)D, alkaline phosphatase, PTH, calcium, phosphate, osteocalcin or bone Gla protein, matrix Gla protein, and vitamin K levels. Vertebral fractures (VFs) and VCs were determined by spine radiograph. A reduction of >20% of vertebral body height was considered a VF. VCs were quantified by the length of calcific lesions along the arteries. The patients treated with oral calcitriol were 177 of 387 patients (45.7%). The prevalence of VF was lower in patients receiving oral calcitriol than in those untreated (48.6% versus 61.0%, p = 0.015), whereas the presence of aortic and iliac calcifications was similar (aortic: 81.9% versus 79.5%, respectively, p = 0.552; iliac: 52.0% and 59.5%, respectively, p = 0.167). In multivariable logistic regression analysis, oral calcitriol was associated with a 40.2% reduced odds of fracture (OR 0.598; 95% confidence interval [CI], 0.363-0.985; p = 0.043). In conclusion, we found a significant association between oral calcitriol and lower VF in HD patients without an increase in the burden of VC. Further prospective and interventional studies are needed to confirm these findings. © 2021 American Society for Bone and Mineral Research (ASBMR).


Subject(s)
Calcitriol , Renal Dialysis , Spinal Fractures/epidemiology , Vitamin K , Calcitriol/administration & dosage , Calcium , Cross-Sectional Studies , Fibroblast Growth Factor-23 , Humans , Parathyroid Hormone , Vitamin D
11.
J Neuroinflammation ; 18(1): 206, 2021 Sep 16.
Article in English | MEDLINE | ID: mdl-34530842

ABSTRACT

BACKGROUND: Glaucoma is an optic neuropathy characterized by loss of function and death of retinal ganglion cells (RGCs), leading to irreversible vision loss. Neuroinflammation is recognized as one of the causes of glaucoma, and currently no treatment is addressing this mechanism. We aimed to investigate the anti-inflammatory and neuroprotective effects of 1,25(OH)2D3 (1α,25-dihydroxyvitamin D3, calcitriol), in a genetic model of age-related glaucomatous neurodegeneration (DBA/2J mice). METHODS: DBA/2J mice were randomized to 1,25(OH)2D3 or vehicle treatment groups. Pattern electroretinogram, flash electroretinogram, and intraocular pressure were recorded weekly. Immunostaining for RBPMS, Iba-1, and GFAP was carried out on retinal flat mounts to assess retinal ganglion cell density and quantify microglial and astrocyte activation, respectively. Molecular biology analyses were carried out to evaluate retinal expression of pro-inflammatory cytokines, pNFκB-p65, and neuroprotective factors. Investigators that analysed the data were blind to experimental groups, which were unveiled after graph design and statistical analysis, that were carried out with GraphPad Prism. Several statistical tests and approaches were used: the generalized estimated equations (GEE) analysis, t-test, and one-way ANOVA. RESULTS: DBA/2J mice treated with 1,25(OH)2D3 for 5 weeks showed improved PERG and FERG amplitudes and reduced RGCs death, compared to vehicle-treated age-matched controls. 1,25(OH)2D3 treatment decreased microglial and astrocyte activation, as well as expression of inflammatory cytokines and pNF-κB-p65 (p < 0.05). Moreover, 1,25(OH)2D3-treated DBA/2J mice displayed increased mRNA levels of neuroprotective factors (p < 0.05), such as BDNF. CONCLUSIONS: 1,25(OH)2D3 protected RGCs preserving retinal function, reducing inflammatory cytokines, and increasing expression of neuroprotective factors. Therefore, 1,25(OH)2D3 could attenuate the retinal damage in glaucomatous patients and warrants further clinical evaluation for the treatment of optic neuropathies.


Subject(s)
Calcitriol/administration & dosage , Glaucoma/metabolism , Glaucoma/prevention & control , Neuroprotective Agents/administration & dosage , Retinal Ganglion Cells/drug effects , Retinal Ganglion Cells/metabolism , Animals , Calcium-Regulating Hormones and Agents/administration & dosage , Female , Gene Regulatory Networks/drug effects , Gene Regulatory Networks/physiology , Glaucoma/genetics , Mice , Mice, Inbred DBA , Mice, Transgenic
13.
J Steroid Biochem Mol Biol ; 214: 105979, 2021 11.
Article in English | MEDLINE | ID: mdl-34438041

ABSTRACT

Chemotherapy is a standard therapeutic option for triple-negative breast cancer (TNBC); however, its effectiveness is often compromised by drug-related toxicity and resistance development. Herein, we aimed to evaluate whether an improved antineoplastic effect could be achieved in vitro and in vivo in TNBC by combining dovitinib, a multi-kinase inhibitor, with calcitriol, a natural anticancer hormone. In vitro, cell proliferation and cell-cycle distribution were studied by sulforhodamine B-assays and flow cytometry. In vivo, dovitinib/calcitriol effects on tumor growth, angiogenesis, and endothelium activation were evaluated in xenografted mice by caliper measures, Itgb3/VEGFR2-immunohistochemistry and 99mTc-Ethylenediamine-N,N-diacetic acid/hydrazinonicotinamyl-Glu[cyclo(Arg-Gly-Asp-D-Phe-Lys)]2 (99mTc-RGD2)-tumor uptake. The drug combination elicited a synergistically improved antiproliferative effect in TNBC-derived cells, which allowed a 7-fold and a 3.3-fold dovitinib dose-reduction in MBCDF-Tum and HCC-1806 cells, respectively. Mechanistically, the co-treatment induced a cell cycle profile suggestive of cell death and DNA damage (accumulation of cells in SubG1, S, and G2/M phases), increased the number of multinucleated cells and inhibited tumor growth to a greater extent than each compound alone. Tumor uptake of 99mTc-RGD2 was reduced by dovitinib, suggesting angiogenesis inhibition, which was corroborated by decreased endothelial cell growth, tumor-vessel density and VEGFR2 expression. In summary, calcitriol synergized dovitinib anticancer effects in vitro and in vivo, allowing for a significant dose-reduction of dovitinib while maintaining its antiproliferative potency. Our results suggest the beneficial convergence of independent antitumor mechanisms of dovitinib and calcitriol to inhibit TNBC-tumor growth.


Subject(s)
Antineoplastic Agents/pharmacology , Benzimidazoles/pharmacology , Calcitriol/pharmacology , Oligopeptides/chemistry , Quinolones/pharmacology , Technetium/chemistry , Triple Negative Breast Neoplasms/drug therapy , Animals , Benzimidazoles/administration & dosage , Calcitriol/administration & dosage , Cell Cycle , Cell Line, Tumor , Cell Proliferation/drug effects , DNA Damage , Dose-Response Relationship, Drug , Female , Humans , Inhibitory Concentration 50 , Integrin beta3/metabolism , Mice , Mice, Nude , Neoplasm Transplantation , Neovascularization, Pathologic , Quinolones/administration & dosage , Single Photon Emission Computed Tomography Computed Tomography , Vascular Endothelial Growth Factor Receptor-2/metabolism
14.
Nutrients ; 13(8)2021 Jul 26.
Article in English | MEDLINE | ID: mdl-34444716

ABSTRACT

BACKGROUND: In COVID-19 patients, low serum vitamin D (VD) levels have been associated with severe acute respiratory failure and poor prognosis. In regular hemodialysis (HD) patients, there is VD deficiency and markedly reduced calcitriol levels, which may predispose them to worse outcomes of COVID-19 infection. Some hemodialysis patients receive treatment with drugs for secondary hyperparathyroidism, which have well known pleiotropic effects beyond mineral metabolism. The aim of this study was to evaluate the impact of VD status and the administration of active vitamin D medications, used to treat secondary hyperparathyroidism, on survival in a cohort of COVID-19 positive HD patients. METHODS: A cross-sectional retrospective observational study was conducted from 12 March to 21 May 2020 in 288 HD patients with positive PCR for SARS-CoV2. Patients were from 52 different centers in Spain. RESULTS: The percent of HD patients with COVID-19 was 6.1% (288 out of 4743). Mortality rate was 28.4% (81/285). Three patients were lost to follow-up. Serum 25(OH)D (calcidiol) level was 17.1 [10.6-27.5] ng/mL and was not significantly associated to mortality (OR 0.99 (0.97-1.01), p = 0.4). Patients receiving active vitamin D medications (16/94 (17%) vs. 65/191(34%), p = 0.003), including calcimimetics (4/49 (8.2%) vs. 77/236 (32.6%), p = 0.001), paricalcitol or calcimimetics (19/117 (16.2%) vs. 62/168 (36.9%); p < 0.001), and also those on both paricalcitol and calcimimetics, to treat secondary hyperparathyroidism (SHPTH) (1/26 (3.8%) vs. 80/259 (30.9%), p < 0.001) showed a lower mortality rate than patients receiving no treatment with either drug. Multivariate Cox regression analysis confirmed this increased survival. CONCLUSIONS: Our findings suggest that the use of paricalcitol, calcimimetics or the combination of both, seem to be associated with the improvement of survival in HD patients with COVID-19. No correlation was found between serum VD levels and prognosis or outcomes in HD patients with COVID-19. Prospective studies and clinical trials are needed to support these findings.


Subject(s)
COVID-19/mortality , Calcitriol/administration & dosage , Ergocalciferols/administration & dosage , Renal Dialysis/mortality , Aged , Aged, 80 and over , COVID-19/blood , Calcifediol/blood , Calcium/blood , Cross-Sectional Studies , Female , Humans , Hyperparathyroidism, Secondary/blood , Hyperparathyroidism, Secondary/drug therapy , Male , Retrospective Studies , SARS-CoV-2/isolation & purification , Survival Analysis , Vitamin D/blood , Vitamin D Deficiency/blood , Vitamin D Deficiency/drug therapy , Vitamin D Deficiency/mortality , Vitamin D Deficiency/virology
15.
Int Immunopharmacol ; 98: 107910, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34198237

ABSTRACT

BACKGROUND: Treatment of vitiligo has several challenges. Phototherapy and topical calcipotriol have been reported to be effective in combination with other therapies, but there is no consensus on the combination use. OBJECTIVE: To perform a systematic review and meta-analysis that elucidates the efficacy of the combination of phototherapy and topical calcipotriol. METHODS: This systematic review was performed by searching PubMed, EMBASE, Web of Science, Cochrane Library databases, Chinese National Knowledge Infrastructure (CNKI), WanFang and VIP databases for relevant publications till February 28, 2021. Relative risk (RR) and its 95% confidence interval (CI) were used to evaluate the data. Bias assessment, heterogeneity and sensitivity analysis were conducted in this meta-analysis. RESULTS: After screening, nine studies with 700 participants were included. The meta-analysis indicated that the combination of phototherapy and topical calcipotriol showed significantly higher effective rate (RR 1.11, 95% CI 1.02-1.22; p < 0.05) and apparent effective rate (RR 1.35, 95% CI 1.15-1.59; p < 0.01) than phototherapy monotherapy in the treatment of vitiligo. In addition, the side effects were minor, transient and tolerable. CONCLUSIONS: This meta-analysis provides evidence supporting phototherapy combined with topical calcipotriol as a valuable treatment modality for patients with vitiligo, which has better efficacy than monotherapy.


Subject(s)
Calcitriol/analogs & derivatives , Dermatologic Agents/administration & dosage , Low-Level Light Therapy/methods , Vitiligo/therapy , Administration, Cutaneous , Calcitriol/administration & dosage , Combined Modality Therapy , Humans , Lasers, Excimer , Low-Level Light Therapy/instrumentation , Randomized Controlled Trials as Topic , Severity of Illness Index , Skin Pigmentation/drug effects , Skin Pigmentation/radiation effects , Treatment Outcome , Vitiligo/diagnosis
16.
Medicine (Baltimore) ; 100(25): e26443, 2021 Jun 25.
Article in English | MEDLINE | ID: mdl-34160437

ABSTRACT

RATIONALE: Autosomal dominant hypocalcaemia type 1 (ADH1) is a genetic disease characterized by benign hypocalcemia, inappropriately low parathyroid hormone levels and mostly hypercalciuria. It is caused by the activating mutations of the calcium-sensing receptor gene (CASR), which produces a left-shift in the set point for extracellular calcium. PATIENT CONCERNS: A 50-year-old man presenting with muscle spasms was admitted into the hospital. He has a positive familial history for hypocalcemia. Auxiliary examinations demonstrated hypocalcemia, hyperphosphatemia, normal parathyroid hormone level and nephrolithiasis. A missense heterozygous variant in CASR, c 613C > T (p. Arg205Cys) which has been reported in a familial hypocalciuric hypercalcemia type 1 patient was found in the patient's genotype. It is the first time that this variant is found associating with ADH1. The variant is predicted vicious by softwares and cosegregates with ADH1 in this pedigree. CASR Arg205Cys was deduced to be the genetic cause of ADH1 in the family. DIAGNOSIS: The patient was diagnosed with ADH1 clinically and genetically. INTERVENTIONS: Oral calcitriol, calcium and hydrochlorothiazide were prescribed to the patient. OUTCOMES: After the treatments for 1 week, the patient's symptom was improved and the re-examination revealed serum calcium in the normal range. A 3-month follow-up showed his symptom was mostly relieved. LESSONS: The variant of CASR Arg205Cys, responsible for ADH1 in this family, broadened the genetic spectrum of ADH1. Further and more studies are required to evaluate the correlation between genotype and phenotype in ADH1 patients.


Subject(s)
Calcium/administration & dosage , Hypercalciuria/diagnosis , Hypocalcemia/diagnosis , Hypoparathyroidism/congenital , Receptors, Calcium-Sensing/genetics , Calcitriol/administration & dosage , Calcium/blood , DNA Mutational Analysis , Drug Therapy, Combination/methods , Female , Genetic Testing , Heterozygote , Humans , Hydrochlorothiazide/administration & dosage , Hypercalciuria/blood , Hypercalciuria/genetics , Hypocalcemia/blood , Hypocalcemia/genetics , Hypoparathyroidism/blood , Hypoparathyroidism/diagnosis , Hypoparathyroidism/genetics , Male , Medical History Taking , Middle Aged , Mutation, Missense , Pedigree , Treatment Outcome
17.
Exp Eye Res ; 209: 108668, 2021 08.
Article in English | MEDLINE | ID: mdl-34144035

ABSTRACT

Vitamin D (VD) deficiency delays corneal wound healing in those with diabetes, which cannot be rescued with supplemental diet. Here, we employed topical calcitriol application to evaluate its efficiency in corneal wound healing and reinnervation in diabetic mice. Type 1 diabetic mice were topically administrated calcitriol, or subconjunctivally injected with NLRP3 antagonist MCC950 or IL-1ß blocking antibody after epithelial debridement. Serum VD levels, corneal epithelial defect, corneal sensation and nerve density, NLRP3 inflammasome activation, neutrophil infiltration, macrophage phenotypes, and gene expressions were examined. Compared with those of normal mice, diabetic mice showed reduced serum VD levels. Topical calcitriol application promoted corneal wound healing and nerve regeneration, as well as sensation recovery in diabetic mice. Moreover, calcitriol ameliorated neutrophil infiltration and promoted the M1-to-M2 macrophage transition, accompanied by suppressed overactivation of the NLRP3 inflammasome. Treatment with NLRP3 antagonist or IL-1ß blockage demonstrated similar improvements as those of topical calcitriol application. Additionally, calcitriol administration upregulated desmosomal and hemidesmosomal gene expression in the diabetic cornea. In conclusion, topical calcitriol application promotes corneal wound healing and reinnervation during diabetes, which may be related to the suppression of the overactivation of NLRP3 inflammasome.


Subject(s)
Calcitriol/administration & dosage , Cornea/innervation , Corneal Diseases/genetics , Diabetes Mellitus, Experimental/complications , Gene Expression Regulation , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Nerve Regeneration/genetics , Animals , Cornea/pathology , Corneal Diseases/etiology , Corneal Diseases/metabolism , Diabetes Mellitus, Experimental/metabolism , Disease Models, Animal , Inflammasomes , Male , Mice , Mice, Inbred C57BL , NLR Family, Pyrin Domain-Containing 3 Protein/biosynthesis , RNA/genetics , Wound Healing/drug effects , Wound Healing/genetics
18.
J Drugs Dermatol ; 20(5): 567-570, 2021 May 01.
Article in English | MEDLINE | ID: mdl-33938704

ABSTRACT

Reduction of psoriasis body surface area (BSA) is associated with improved patient quality of life. Post-hoc analyses of the PSO-LONG study compared impact on BSA of proactive management versus reactive management strategies using calcipotriol/betamethasone dipropionate (Cal/BD) foam. Mean BSA values, as well as normalized area under the curves (AUCs) for patient BSA were assessed. Analyses found that after the PSO-LONG study’s four-week open-label lead-in phase, when all patients received once-daily Cal/BD foam, mean BSA was significantly reduced. Thereafter, mean BSA remained at lower levels in patients on proactive management compared to reactive management. This was reflected in AUC BSA, which was consistently lower in the proactive management arm. Treatment-related differences were statistically significant when analyzing the full analysis set (FAS) population, as well as when restricting the analysis to study completers. Additional analyses restricted the dataset to include only observations from psoriasis remission periods, or periods of disease relapse. Treatment-related differences in AUC were statistically significant in observations during remission, but not during relapse. This could be expected given the trial’s design, wherein all patients who relapsed were offered the same rescue therapy with once daily Cal/BD foam. Similarly, for patients who dropped out, there was no treatment-related difference in mean BSA during the two weeks preceding dropout, likely due to the common occurrence of relapse in these patients. This paper found that proactive management, in addition to preventing more relapses as previously shown, also maintained BSA at a lower level during remission than reactive management. J Drugs Dermatol. 20(5):567-570. doi:10.36849/JDD.5870.


Subject(s)
Betamethasone/analogs & derivatives , Calcitriol/analogs & derivatives , Dermatologic Agents/administration & dosage , Psoriasis/drug therapy , Severity of Illness Index , Aerosols , Betamethasone/administration & dosage , Body Surface Area , Calcitriol/administration & dosage , Drug Administration Schedule , Drug Combinations , Humans , Maintenance Chemotherapy/methods , Psoriasis/diagnosis , Psoriasis/psychology , Quality of Life , Recurrence , Remission Induction/methods , Secondary Prevention/methods , Treatment Outcome
19.
Dermatol Surg ; 47(4): e111-e116, 2021 04 01.
Article in English | MEDLINE | ID: mdl-33795567

ABSTRACT

BACKGROUND: Nail psoriasis is a common and potentially debilitating condition for which no effective and safe nonsystemic therapy is currently available. Recently, laser-assisted drug delivery (LADD) is being increasingly used to facilitate transcutaneous penetration of topical treatments. OBJECTIVES: We set to assess the efficacy and safety of combined pulse-dye laser and fractional CO2 laser-assisted betamethasonecalcipotriol gel delivery for the treatment of nail psoriasis. MATERIAL AND METHODS: We conducted a prospective, intrapatient comparative study in a series of 22 patients with bilateral fingernail psoriasis. Nails on the randomized hand were treated with 3 monthly sessions of pulse-dye laser to the proximal and lateral nail folds followed by fractional ablative CO2 laser to the nail plate. Between treatments and one month following the last treatment, the participants applied betamethasone propionate-calcipotriol gel once daily to the nail plate. Clinical outcome was ascertained using nails photography, the Nail Psoriasis Severity Index (NAPSI) and patient satisfaction. RESULTS: Seventeen completed the study. Three participants withdrew from the study because of treatment-associated pain. Treatment was associated with a statistically significant improvement of the NAPSI scale (p < .002). Patient satisfaction was high. CONCLUSION: Combined PDL and fractional ablative CO2-LADD of betamethasone-calcipotriol gel should be considered for the treatment of nail psoriasis.


Subject(s)
Betamethasone/administration & dosage , Calcitriol/analogs & derivatives , Lasers, Dye/therapeutic use , Nail Diseases/therapy , Psoriasis/therapy , Administration, Topical , Adult , Calcitriol/administration & dosage , Dermatologic Agents/administration & dosage , Drug Combinations , Female , Follow-Up Studies , Glucocorticoids/administration & dosage , Humans , Male , Middle Aged , Nail Diseases/diagnosis , Prospective Studies , Psoriasis/diagnosis , Young Adult
20.
J Drugs Dermatol ; 20(4): 420-425, 2021 Apr 01.
Article in English | MEDLINE | ID: mdl-33852251

ABSTRACT

BACKGROUND: The fixed dose combination of calcipotriene and betamethasone dipropionate (CAL/BDP) is a well-established, efficacious, and safe topical treatment of psoriasis. METHOD: A Phase 3, multicenter, randomized, investigator-blind, active, and vehicle-controlled trial enrolling 796 patients with moderate to severe psoriasis according to the Physician Global Assessment (PGA) scale. Products were applied once daily for 8 weeks. RESULTS: The proportion of patients achieving PGA treatment success after 8 weeks was statistically significantly greater for CAL/BDP cream (37.4%) compared to CAL/BDP TS (22.8%, P<0.0001), and vehicle (3.7%, P<0.0001). A similar statistically significant difference in favor of CAL/BDP cream at week 8 was demonstrated for the percentage change in mPASI from baseline and the proportion of patients obtaining mPASI75. Patient reported treatment convenience for CAL/BDP cream was rated superior to CAL/BDP TS. Safety assessments during the trial demonstrated that CAL/BDP cream was well-tolerated with no adverse reactions with a frequency greater than 1%. CONCLUSION: CAL/BDP cream is a novel topical treatment of psoriasis, which in a single product, offers a unique combination of high efficacy combined with favorable safety and excellent treatment convenience. For these reasons, CAL/BDP cream offers a distinctive advantage for the topical treatment of plaque psoriasis. ClinicalTrials.gov: NCT03308799J Drugs Dermatol. 20(4):420-425. doi:10.36849/JDD.5653.


Subject(s)
Betamethasone/analogs & derivatives , Calcitriol/analogs & derivatives , Dermatologic Agents/administration & dosage , Psoriasis/drug therapy , Skin Cream/administration & dosage , Adult , Aged , Betamethasone/administration & dosage , Betamethasone/adverse effects , Calcitriol/administration & dosage , Calcitriol/adverse effects , Dermatologic Agents/adverse effects , Drug Combinations , Female , Humans , Male , Middle Aged , Psoriasis/diagnosis , Skin Cream/adverse effects , Treatment Outcome
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