The Experts below are selected from a list of 2010 Experts worldwide ranked by ideXlab platform
Elena Levtchenko - One of the best experts on this subject based on the ideXlab platform.
-
ophthalmic outcome in a belgian cohort of cystinosis patients treated with a compounded preparation of cysteamine eye drops retrospective analysis
Ophthalmology and therapy, 2019Co-Authors: Freya Peeters, Elena Levtchenko, Catherine Cassiman, Karel Van Keer, Koenraad Veys, Ingele CasteelsAbstract:Introduction Treatment of the anterior segment problems in cystinosis is challenging as oral cysteamine is ineffective in the treatment of corneal problems because of its avascular structure. Although cysteamine eye drops have been formulated to counter this issue, the stability of cysteamine in these off-licensed formulations and treatment compliance are major problems. The aim of this retrospective study was to determine the efficacy of a compounded preparation of aqueous 0.5% cysteamine eye drops in the management of corneal complications of cystinosis.
-
cysteamine an old drug with new potential
Drug Discovery Today, 2013Co-Authors: Martine T P Besouw, Elena Levtchenko, Rosalinde Masereeuw, Lambert P Van Den HeuvelAbstract:Cysteamine is an amino thiol with the chemical formula HSCH2CH2NH2. Endogenously, cysteamine is derived from coenzyme A degradation, although its plasma concentrations are low. Most experience with cysteamine as a drug originates from the field of the orphan disease cystinosis, in which cysteamine is prescribed to decrease intralysosomal cystine accumulation. However, over the years, the drug has been used for several other applications both in vitro and in vivo. In this article, we review the different applications of cysteamine, ending with an overview of ongoing clinical trials for new indications, such as neurodegenerative disorders and nonalcoholic fatty liver disease (NAFLD). The recent development of an enteric-coated cysteamine formulation makes cysteamine more patient friendly and will extend its applicability for both old and new indications.
-
the origin of halitosis in cystinotic patients due to cysteamine treatment
Molecular Genetics and Metabolism, 2007Co-Authors: Martine T P Besouw, Henk J Blom, Addy C De Graafhess, A Tangerman, Elena LevtchenkoAbstract:INTRODUCTION: Cystinosis is a rare autosomal recessive disorder characterized by the intralysosomal accumulation of cystine. Cysteamine removes cystine from the lysosome and slows down the progression of the disease. One of its side effects is the induction of halitosis, which can interfere with patients' willingness to comply with cysteamine treatment. OBJECTIVE: To identify breath sulphur compounds causing halitosis induced by cysteamine therapy in patients with cystinosis. STUDY DESIGN: After the ingestion of 15mg/kg cysteamine whole blood (n=4), urine (n=4) and breath (n=8) volatile sulphur compounds levels were measured every 60min over a 360min period by gas chromatography and the cysteamine plasma concentrations (n=4) were measured by high-performance liquid chromatography. RESULTS: The expired air of cystinotic patients contained elevated concentrations of methanethiol (MT, median maximum value 0.5 (range 0-11)nmol/L) and, in particular, dimethylsulphide (DMS, median maximum value 15 (range 2-83)nmol/L). DMS concentrations higher than 0.65nmol/L are known to cause halitosis. Maximal plasma values of cysteamine (median 46 (range 30-52)micromol/L) preceded those of MT and DMS, confirming that cysteamine is converted to MT and DMS. Less than 3% of the amount of cysteamine ingested was excreted as MT and DMS via expired air and 0.002% via urine. CONCLUSION: Halitosis induced by cysteamine intake is caused by DMS and to a lesser extent by MT, excreted via the expired air. Further studies should focus on the possibilities of reducing the formation of these volatile sulphur compounds or masking their odour, which would improve the rates of compliance with cysteamine treatment.
-
strict cysteamine dose regimen is required to prevent nocturnal cystine accumulation in cystinosis
Pediatric Nephrology, 2006Co-Authors: Elena Levtchenko, Leo A H Monnens, Lambertus P Van Den Heuvel, Martijn J Wilmer, Carin M Van Dael, Addy C De Graafhess, Henk J BlomAbstract:Cystinosis is an autosomal recessive disorder, caused by mutations in the lysosomal cystine carrier cystinosin, encoded by the CTNS gene. The disease generally manifests with Fanconi syndrome during the first year of life and progresses towards end stage renal disease before the age of 10 years. Cysteamine depletes intralysosomal cystine content, postpones the deterioration of renal function and the occurrence of extra-renal organ damage. Based on the pharmacokinetic data, patients with cystinosis are advised to use cysteamine every 6 h. The aim of this study was (1) to evaluate the cysteamine dose regimen in Dutch patients with cystinosis and (2) to determine morning polymorphonuclear (PMN) leukocyte cystine content 6 h vs 9 h after the last evening cysteamine dose. Only 5/22 of Dutch cystinosis patients ingested cysteamine every 6 h. Morning (8 a.m.) PMN cystine content in 11 examined patients was elevated 9 h after 12.5-15 mg/kg evening cysteamine dose compared to the value 6 h after the ingestion of the same dose (0.73+/-0.81 nmol vs 0.44+/-0.52 nmol cystine/mg protein, p =0.02). In conclusion, only the minority of Dutch cystinosis patients follows the recommended strict cysteamine dose regimen. We provide evidence that cysteamine has to be administered every 6 h, including the night, as it has much better effect for maintaining low PMN cystine levels.
Behrooz Kasraee - One of the best experts on this subject based on the ideXlab platform.
-
evaluation of the efficacy of cysteamine 5 cream in the treatment of epidermal melasma a randomized double blind placebo controlled trial
British Journal of Dermatology, 2015Co-Authors: Parvin Mansouri, Susan Farshi, Z Hashemi, Behrooz KasraeeAbstract:SummaryBackground Melasma is a difficult-to-treat hyperpigmentary disorder. While cysteamine is a known potent depigmenting agent, its efficacy in treating melasma has not been tested. Objectives To study the efficacy of cysteamine 5% cream in the treatment of patients with epidermal melasma. Methods In this double-blind randomized study, participating patients (n = 50) received either placebo (n = 25) or cysteamine cream (n = 25). Cysteamine cream or placebo were applied on the lesions once a day at bedtime over 4 months. The efficacy of treatments was determined through Mexameter skin colorimetry, Melasma Area Severity Index (MASI) score, Investigator's Global Assessment (IGA) and patients’ questionnaires, all performed at baseline and after 2 and 4 months of treatment. Results At baseline, the mean differences between pigmented and normal skin (calculated by Mexameter) were 75·2 ± 37 and 68·9 ± 31 in the cysteamine and placebo groups, respectively. After 2 and 4 months of application of cysteamine and placebo cream, the mean differences were 39·7 ± 16·6 and 26·2 ± 16 in the cysteamine group, and 63·8 ± 28·6 and 60·7 ± 27·3 in the placebo group, respectively. Statistically significant differences were found between the group outcomes at both points (P = 0·001 and P < 0·001). At the end of the treatment, the MASI scores were significantly lower in the cysteamine group vs. placebo (7·2 ± 5·5 vs. 11·6 ± 7·9, P = 0·02). The IGA and patients’ viewpoints indicated significant efficacy of cysteamine cream vs. placebo. Conclusions Cysteamine cream showed significant efficacy in the treatment of melasma.
-
evaluation of the efficacy of cysteamine 5 cream in the treatment of epidermal melasma a randomized double blind placebo controlled trial
British Journal of Dermatology, 2015Co-Authors: Parvin Mansouri, Susan Farshi, Z Hashemi, Behrooz KasraeeAbstract:Background Melasma is a difficult-to-treat hyperpigmentary disorder. While cysteamine is a known potent depigmenting agent, its efficacy in treating melasma has not been tested. Objectives To study the efficacy of cysteamine 5% cream in the treatment of patients with epidermal melasma. Methods In this double-blind randomized study, participating patients (n = 50) received either placebo (n = 25) or cysteamine cream (n = 25). Cysteamine cream or placebo were applied on the lesions once a day at bedtime over 4 months. The efficacy of treatments was determined through Mexameter skin colorimetry, Melasma Area Severity Index (MASI) score, Investigator's Global Assessment (IGA) and patients' questionnaires, all performed at baseline and after 2 and 4 months of treatment. Results At baseline, the mean differences between pigmented and normal skin (calculated by Mexameter) were 75.2 ± 37 and 68.9 ± 31 in the cysteamine and placebo groups, respectively. After 2 and 4 months of application of cysteamine and placebo cream, the mean differences were 39.7 ± 16.6 and 26.2 ± 16 in the cysteamine group, and 63.8 ± 28.6 and 60.7 ± 27.3 in the placebo group, respectively. Statistically significant differences were found between the group outcomes at both points (P = 0.001 and P Conclusions Cysteamine cream showed significant efficacy in the treatment of melasma.
Jess G Thoene - One of the best experts on this subject based on the ideXlab platform.
-
characterization of cysteamine as a potential contraceptive anti hiv agent
Journal of Andrology, 1998Co-Authors: Robert A Anderson, Kenneth A Feathergill, Risa Kirkpatrick, Lourens J D Zaneveld, Kevin T Coleman, Patricia G Spear, Morris D Cooper, Donald P Waller, Jess G ThoeneAbstract:Cysteamine (-mercaptoethylamine, or MEA) is a thi- 01-reducing agent and has anti-HIV activity. Because of these prop- erties, cysteamine was evaluated as a vaginal contraceptive and tested for its effects on sperm function and on other sexually trans- miffed microbes. Cysteamine was contraceptive in the rabbit. Con- ception was inhibited completely when sperm were pretreated with 500 1i.g/ml cysteamine and was inhibited by more than 60% when 7.5 mg cysteamine was applied vaginally as a suspension in 50% K-V Jelly. Cysteamine had multiple effects on spermatozoa. Both acrosin (EC 3.4.21.10) and hyaluronidase (EC 3.2.1.35) were re- versibly inhibited by cysteamine. Calculated lCw values were 370 p.g/ml and 150 p.g/ml for acrosin and hyaluronidase, respectively. Cysteamine behaved as a poor spermicide when activity was mea- sured by the 30-second Sander-Cramer test. However, sperm mo- tility was inhibited completely when cysteamine was preincubated for 10 minutes prior to motility evaluation, at concentrations as low as 50 ii.g/ml. The calcium ionophore A231 87-induced human acro- some reaction was inhibited by cysteamine (lC = 0.5 g/ml). Nei- ther herpes simplex virus nor Neisseria gonorrhoeae was affected by cysteamine at concentrations as high as 500 g/ml and 100 p.g/ ml, respectively. Cysteamine appears to have no effect on normal vaginal flora (i.e., lactobacillus). These results, together with pub- lished data, strongly support the further development of cysteamine as a topical contraceptive anti-HIV agent.
Levtchenko E.n. - One of the best experts on this subject based on the ideXlab platform.
-
Increased human dermal microvascular endothelial cell survival induced by cysteamine
'Springer Science and Business Media LLC', 2013Co-Authors: Besouw M., Heuvel, L.p. Van Den, Eijsden R. Van, Kluijtmans L.a., Dewerchin M., Levtchenko E.n.Abstract:Item does not contain fulltextBACKGROUND: Cystinosis is an autosomal recessive disease caused by intralysosomal cystine accumulation, treated with cysteamine. Recently, new adverse effects of cysteamine were reported. Skin biopsies showed microvascular proliferation (angioendotheliomatosis). To examine the mechanism of angioendotheliomatosis associated with cysteamine toxicity, we examined the effect of cysteamine on human dermal microvascular endothelial cells (HDMVEC). METHODS: After cysteamine exposure (range 0-3.0 mM) during 24 h, cell viability was measured using water soluble tetrazolium salt-1 (WST-1) in both control HDMVEC and fibroblasts. Cell proliferation and apoptosis rate were measured in HDMVEC by bromodeoxyuridine (BrdU) incorporation and caspase 3 and caspase 7 activity, respectively. Intracellular glutathione (GSH) was measured in HDMVEC after cysteamine exposure of 0, 0.1 or 1.0 mM. Medium and cysteamine were refreshed every 6 h to mimic the in vivo situation. Next, cell viability in HDMVEC was measured after 24 h of GSH exposure (range 0-10.0 mM). RESULTS: HDMVEC viability and proliferation increased after cysteamine exposure 0.03-3.0 mM (p < 0.01) and 0.03-1.0 mM (p = 0.01) respectively; cell viability in fibroblasts was not affected by incubation with cysteamine. Apoptosis remained unaffected by incubation with 0-1.0 mM cysteamine, 3.0 mM caused increased apoptosis. Intracellular GSH was significantly increased after incubation with cysteamine 0.1 mM (p = 0.02) and 1.0 mM (p < 0.01). HDMVEC viability increased after exposure to GSH 1.0-5.0 mM (p < 0.01). CONCLUSION: Cysteamine concentrations, similar to those described in plasma of cystinosis patients, stimulate HDMVEC viability and proliferation and increase intracellular GSH content. We postulate that this mechanism might underlie angioendotheliomatosis induced by cysteamine
-
Increased human dermal microvascular endothelial cell survival induced by cysteamine
2013Co-Authors: Besouw M., Heuvel, L.p. Van Den, Eijsden R. Van, Kluijtmans L.a., Dewerchin M., Levtchenko E.n.Abstract:BACKGROUND: Cystinosis is an autosomal recessive disease caused by intralysosomal cystine accumulation, treated with cysteamine. Recently, new adverse effects of cysteamine were reported. Skin biopsies showed microvascular proliferation (angioendotheliomatosis). To examine the mechanism of angioendotheliomatosis associated with cysteamine toxicity, we examined the effect of cysteamine on human dermal microvascular endothelial cells (HDMVEC). METHODS: After cysteamine exposure (range 0-3.0 mM) during 24 h, cell viability was measured using water soluble tetrazolium salt-1 (WST-1) in both control HDMVEC and fibroblasts. Cell proliferation and apoptosis rate were measured in HDMVEC by bromodeoxyuridine (BrdU) incorporation and caspase 3 and caspase 7 activity, respectively. Intracellular glutathione (GSH) was measured in HDMVEC after cysteamine exposure of 0, 0.1 or 1.0 mM. Medium and cysteamine were refreshed every 6 h to mimic the in vivo situation. Next, cell viability in HDMVEC was measured after 24 h of GSH exposure (range 0-10.0 mM). RESULTS: HDMVEC viability and proliferation increased after cysteamine exposure 0.03-3.0 mM (p < 0.01) and 0.03-1.0 mM (p = 0.01) respectively; cell viability in fibroblasts was not affected by incubation with cysteamine. Apoptosis remained unaffected by incubation with 0-1.0 mM cysteamine, 3.0 mM caused increased apoptosis. Intracellular GSH was significantly increased after incubation with cysteamine 0.1 mM (p = 0.02) and 1.0 mM (p < 0.01). HDMVEC viability increased after exposure to GSH 1.0-5.0 mM (p < 0.01). CONCLUSION: Cysteamine concentrations, similar to those described in plasma of cystinosis patients, stimulate HDMVEC viability and proliferation and increase intracellular GSH content. We postulate that this mechanism might underlie angioendotheliomatosis induced by cysteamine
-
Strict cysteamine dose regimen is required to prevent nocturnal cystine accumulation in cystinosis.
'Springer Science and Business Media LLC', 2006Co-Authors: Levtchenko E.n., Wilmer M.j.g., Heuvel, L.p.w.j. Van Den, Dael, C.m. Van, A.c. De ,graaf-hess, Monnens L.a.h., Blom H.j.Abstract:Contains fulltext : 49692.pdf (publisher's version ) (Closed access)Cystinosis is an autosomal recessive disorder, caused by mutations in the lysosomal cystine carrier cystinosin, encoded by the CTNS gene. The disease generally manifests with Fanconi syndrome during the first year of life and progresses towards end stage renal disease before the age of 10 years. Cysteamine depletes intralysosomal cystine content, postpones the deterioration of renal function and the occurrence of extra-renal organ damage. Based on the pharmacokinetic data, patients with cystinosis are advised to use cysteamine every 6 h. The aim of this study was (1) to evaluate the cysteamine dose regimen in Dutch patients with cystinosis and (2) to determine morning polymorphonuclear (PMN) leukocyte cystine content 6 h vs 9 h after the last evening cysteamine dose. Only 5/22 of Dutch cystinosis patients ingested cysteamine every 6 h. Morning (8 a.m.) PMN cystine content in 11 examined patients was elevated 9 h after 12.5-15 mg/kg evening cysteamine dose compared to the value 6 h after the ingestion of the same dose (0.73+/-0.81 nmol vs 0.44+/-0.52 nmol cystine/mg protein, p =0.02). In conclusion, only the minority of Dutch cystinosis patients follows the recommended strict cysteamine dose regimen. We provide evidence that cysteamine has to be administered every 6 h, including the night, as it has much better effect for maintaining low PMN cystine levels
Parvin Mansouri - One of the best experts on this subject based on the ideXlab platform.
-
efficacy of cysteamine cream in the treatment of epidermal melasma evaluating by dermacatch as a new measurement method a randomized double blind placebo controlled study
Journal of Dermatological Treatment, 2018Co-Authors: Susan Farshi, Parvin MansouriAbstract:AbstractBackground: Melasma is a difficult-to-treat hyperpigmentary disorder. Very few studies have been performed regarding the efficacy of cysteamine in the treatment of melasma.Objective: To determine the efficacy of cysteamine cream in the treatment of patients with epidermal melasma using Dermacatch® as a more accurate skin colorimetric measurement tool.Methods: Participating patients (n = 40) received either placebo (n = 20) or cysteamine cream (n = 20) in a double-blind placebo controlled study. Cysteamine cream or placebo was applied on the lesions once a day at bedtime throughout the four-month study period. Treatment efficacy was determined through Dermacatch® and Mexameter® skin colorimetry, MASI scores, Investigator Global Assessments (IGAs), and patient questionnaires, all performed at baseline, 2-month, and 4-month examinations.Results: Prior to the start of the protocol, the mean difference between pigmented and normal skin was calculated for cysteamine and placebo groups using both Dermaca...
-
evaluation of the efficacy of cysteamine 5 cream in the treatment of epidermal melasma a randomized double blind placebo controlled trial
British Journal of Dermatology, 2015Co-Authors: Parvin Mansouri, Susan Farshi, Z Hashemi, Behrooz KasraeeAbstract:SummaryBackground Melasma is a difficult-to-treat hyperpigmentary disorder. While cysteamine is a known potent depigmenting agent, its efficacy in treating melasma has not been tested. Objectives To study the efficacy of cysteamine 5% cream in the treatment of patients with epidermal melasma. Methods In this double-blind randomized study, participating patients (n = 50) received either placebo (n = 25) or cysteamine cream (n = 25). Cysteamine cream or placebo were applied on the lesions once a day at bedtime over 4 months. The efficacy of treatments was determined through Mexameter skin colorimetry, Melasma Area Severity Index (MASI) score, Investigator's Global Assessment (IGA) and patients’ questionnaires, all performed at baseline and after 2 and 4 months of treatment. Results At baseline, the mean differences between pigmented and normal skin (calculated by Mexameter) were 75·2 ± 37 and 68·9 ± 31 in the cysteamine and placebo groups, respectively. After 2 and 4 months of application of cysteamine and placebo cream, the mean differences were 39·7 ± 16·6 and 26·2 ± 16 in the cysteamine group, and 63·8 ± 28·6 and 60·7 ± 27·3 in the placebo group, respectively. Statistically significant differences were found between the group outcomes at both points (P = 0·001 and P < 0·001). At the end of the treatment, the MASI scores were significantly lower in the cysteamine group vs. placebo (7·2 ± 5·5 vs. 11·6 ± 7·9, P = 0·02). The IGA and patients’ viewpoints indicated significant efficacy of cysteamine cream vs. placebo. Conclusions Cysteamine cream showed significant efficacy in the treatment of melasma.
-
evaluation of the efficacy of cysteamine 5 cream in the treatment of epidermal melasma a randomized double blind placebo controlled trial
British Journal of Dermatology, 2015Co-Authors: Parvin Mansouri, Susan Farshi, Z Hashemi, Behrooz KasraeeAbstract:Background Melasma is a difficult-to-treat hyperpigmentary disorder. While cysteamine is a known potent depigmenting agent, its efficacy in treating melasma has not been tested. Objectives To study the efficacy of cysteamine 5% cream in the treatment of patients with epidermal melasma. Methods In this double-blind randomized study, participating patients (n = 50) received either placebo (n = 25) or cysteamine cream (n = 25). Cysteamine cream or placebo were applied on the lesions once a day at bedtime over 4 months. The efficacy of treatments was determined through Mexameter skin colorimetry, Melasma Area Severity Index (MASI) score, Investigator's Global Assessment (IGA) and patients' questionnaires, all performed at baseline and after 2 and 4 months of treatment. Results At baseline, the mean differences between pigmented and normal skin (calculated by Mexameter) were 75.2 ± 37 and 68.9 ± 31 in the cysteamine and placebo groups, respectively. After 2 and 4 months of application of cysteamine and placebo cream, the mean differences were 39.7 ± 16.6 and 26.2 ± 16 in the cysteamine group, and 63.8 ± 28.6 and 60.7 ± 27.3 in the placebo group, respectively. Statistically significant differences were found between the group outcomes at both points (P = 0.001 and P Conclusions Cysteamine cream showed significant efficacy in the treatment of melasma.
