Combination of 5% cysteamine and 4% nicotinamide in melasma: Efficacy, tolerability, and safety.

BACKGROUND: Melasma is a chronic dermatosis that impacts the patient's quality of life and can present considerable challenges in terms of effective treatment. OBJECTIVE: To evaluate the effectiveness, tolerability, and safety of 5% cysteamine combined with 4% nicotinamide in female subjects with melasma. METHODS: This single-center, single-arm, prospective, open-label study evaluated patients with melasma using a combination cream of 5% cysteamine and 4% nicotinamide in a progressive regimen (60 min in the first month, 120 min in the second month, and 180 min in the third month). RESULTS: Overall, 35 treated subjects exhibited reduced modified Melasma Area and Severity Index (mMASI) (p < 0.001) and decreased MelasQoL scores (p < 0.001), accompanied by improved brightness, luminosity, homogeneity, and spot intensity (p < 0.001). Photographic and colorimetric analysis revealed smaller spots and improved homogeneity. LIMITATIONS: Adherence to progressive daily treatment could not be evaluated long-term. CONCLUSION: A combination cream comprising 5% cysteamine and 4% nicotinamide was effective, tolerable, and safe for treating melasma.

Cysteamine Isobionic-Amide Complex Versus Kligman's Formula for the Treatment of Melasma: Equal Efficacy and Rapid Onset of Action.

BACKGROUND: Modified Kligman's formula (mKF) is the gold standard treatment for melasma; however, its prolonged use is not recommended due to side effects. Cysteamine is a potent, safe, and effective depigmenting agent. Here, we conducted a double-blind, randomized, and placebo-controlled clinical trial to assess the efficacy of cysteamine isobionic-amide -- a complex with enhanced depigmenting efficacy -- and compared it to mKF for the treatment of melasma. METHODS: This study involved a total of 80 patients divided into 3 groups: cysteamine-isobionic amide, placebo, or mKF. The modified Melasma Area Severity Index (mMASI) score and spectrophotometric evaluation were conducted at baseline, week 4, week 8, and week 16. Dermatological assessment, patients’ feedback, and satisfaction including quality-of-life scores were also collected. RESULTS: At week 4, cysteamine isobionic-amide and mKF groups showed an equivalent onset of action in terms of mMASI and skin pigmentation contrast reduction. The 2 groups significantly reduced melasma severity and improved the overall skin condition with a comparable efficacy at week 16. Quality of life of melasma patients was significantly improved in the cysteamine isobionic-amide group at week 8 and further at week 16 (P<0.001) compared to the mKF group. Patients’ feedback and satisfaction were higher with the cysteamine isobionic-amide product compared to mKF. CONCLUSION: Cysteamine isobionic-amide provided a rapid onset of action and was as effective as the mKF for the treatment of melasma. The data suggest that cysteamine isobionic-amide could potentially be an acceptable alternative to mKF for the long-term treatment of melasma. J Drugs Dermatol. 2024;23(2):9-16.  doi:10.36849/JDD.7428.

Cystinosis: Status of research and treatment in India and the world.

Cystinosis is an autosomally inherited rare genetic disorder in which cystine accumulates in the lysosome. The defect arises from a mutation in the lysosomal efflux pump, cystinosin (or CTNS). Despite the disease being known for more than a century, research, diagnosis, and treatment in India have been very minimal. In recent years, however, some research on cystinosis has been carried out on understanding the pathophysiology and in the development of a humanized yeast model for interrogating the CTNS protein. There has also been a greater awareness of the disease that has been facilitated by the formation of the Cystinosis Foundation of India just over a decade ago. Awareness among primary physicians is critical for early diagnosis, which in turn is critical for proper treatment. Eight different mutations have been observed in cystinosis patients in India, and the mutation spectrum seems different to what has been seen in the US and Europe. Despite these positive developments, there are immense hurdles still to be surmounted. This includes ensuring that the diagnosis is done sooner, making cysteamine more easily available, and, also for the future, to make accessible the promise of gene therapy to cystinosis patients.

The effects of transitioning from immediate release to extended release cysteamine therapy in Norwegian patients with nephropathic cystinosis: a retrospective study.

BACKGROUND: Nephropathic cystinosis is a rare lysosomal storage disorder in which accumulation of cystine and formation of crystals particularly impair kidney function and gradually lead to multi-organ dysfunction. Lifelong therapy with the aminothiol cysteamine can delay the development of kidney failure and the need for transplant. The purpose of our long-term study was to explore the effects of transitioning from immediate release (IR) to extended release (ER) formulation in Norwegian patients in routine clinical care. METHODS: We retrospectively analysed data on efficacy and safety in 10 paediatric and adult patients. Data were obtained from up to 6 years before and 6 years after transitioning from IR- to ER-cysteamine. RESULTS: Mean white blood cell (WBC) cystine levels remained comparable between the different treatment periods (1.19 versus 1.38 nmol hemicystine/mg protein) although most patients under ER-cysteamine underwent dose reductions. For the non-transplanted patients, the mean estimated glomerular filtration rate (eGFR) change/year was more pronounced during ER-treatment (- 3.39 versus - 6.80 ml/min/1.73 m2/year) possibly influenced by individual events, such as tubulointerstitial nephritis and colitis. Growth measured by Z-height score tended to develop positively. Four of seven patients reported improvement of halitosis, one reported unchanged and two reported worsened symptoms. Most adverse drug reactions (ADRs) were of mild severity. One patient developed two serious ADRs and switched back to IR-formulation. CONCLUSIONS: The results from this long-term retrospective study indicate that switching from IR- to ER-cysteamine was feasible and well tolerated under routine clinical practice. ER-cysteamine allowed satisfactory disease control over the long period considered. A higher resolution version of the Graphical abstract is available as Supplementary information.

[Cystinosis: From the gene identification to the first gene therapy clinical trial]. / Cystinose - De la découverte du gène aux premiers essais de thérapie génique.

Cystinosis is an autosomal recessive metabolic disease characterized by lysosomal accumulation of cystine in all the cells of the body. Infantile cystinosis begins in infancy by a renal Fanconi syndrome and eventually leads to multi-organ failure, including the kidney, eye, thyroid, muscle, and pancreas, eventually causing premature death in early adulthood. The current treatment is the drug cysteamine that only delays the progression of the disease. We identified the gene involved, CTNS, and showed that the encoded protein, cystinosin, is a proton-driven cystine transporter. We generated a mouse model of cystinosis, the Ctns-/- mice, that recapitulates the main disease complications. The goal was next to develop a gene therapy approach for cystinosis. We used bone marrow stem cells as a vehicle to bring the healthy CTNS gene to tissues, and we showed that wild-type hematopoietic stem and progenitor cell (HSPC) transplantation led to abundant tissue integration of bone marrow-derived cells, significant decrease of tissue cystine accumulation and long-term kidney, eye and thyroid preservation. We then developed an autologous transplantation approach of HSPCs modified ex vivo using a lentiviral vector to introduce a functional CTNS cDNA, and showed its efficacy in Ctns-/- mice. We conducted the pharmacology/toxicology studies, developed the manufacturing process using human CD34+ cells, and design the clinical trial. We received Food and Drug Administration (FDA)-clearance to start a phase 1/2 clinical trial for cystinosis in December 2018. Six patients have been treated so far. In this review, we describe the path to go from the gene to a gene therapy approach for cystinosis.

Title: Cystinose - De la découverte du gène aux premiers essais de thérapie génique. Abstract: La cystinose est une maladie métabolique autosomique récessive caractérisée par une accumulation lysosomale de cystine dans toutes les cellules de l'organisme. La cystinose infantile débute dans la petite enfance par un syndrome de Fanconi et aboutit à une détérioration progressive de la fonction de la plupart des organes, y compris les reins, les yeux, la thyroïde, les muscles et le pancréas, et finit par entraîner une mort prématurée. Le traitement par la cystéamine ne permet que de retarder la progression de la maladie. Afin de développer une approche de thérapie génique pour la cystinose, un modèle murin qui présente les principales complications de la maladie a été développé grâce à l'identification du gène CTNS, dont le produit, la cystinosine, est un co-transporteur de cystine-protons. Cette revue décrit les étapes allant de la découverte du gène à la thérapie génique pour la cystinose, qui a permis de traiter six patients jusqu'à présent.

A new proof of evidence of cysteamine quantification for therapeutic drug monitoring in patients with cystinosis.

BACKGROUND: To date, measurement of intracellular cystine is used for the therapeutic monitoring of patients affected by cystinosis in treatment with cysteamine. Since this method is time and sample consuming, development of a faster method to quantify cysteamine would be extremely useful in order to help clinicians to adjust dosages of cysteamine and to define better the pharmacokinetic profile of this drug. The aim of the study was to develop a liquid chromatography tandem mass spectrometry method for the quantification of cysteamine in plasma samples and to test its applicability on plasma samples derived from patients with nephropathic infantile cystinosis in treatment with cysteamine. RESULTS: The percentage of accuracy of the developed method varied between 97.80 and 106.00% and CV% between 0.90 and 6.93%. There was no carry over. The calibration curves were built from 2.5 to 50 µM. The limit of detection and the lower limit of quantification occurred at 0.25 and 1.25 µM respectively. Cysteamine was stable up to 2 months at -20 °C. Concentrations of cysteamine and intracellular cystine of 4 patients were in line with data previously reported. CONCLUSION: The proposed method showed an appropriate selectivity, specificity, linearity, sensibility, accuracy, precision and good applicability to samples.

Is cysteamine use effective in the treatment of melasma? A systematic review and meta-analysis.

Melasma is a recurrent hypermelanosis disorder characterized by the appearance of brownish and symmetrical spots on the skin. It affects the quality of life and is resistant to available treatment approaches. Cysteamine has been reported as a promising depigmenting agent for melasma treatment and following formulation enhancement, its use is being reported. This review aimed to evaluate the efficacy of the use of depigmenting formulations containing 5% cysteamine in the treatment of patients with melasma. A systematic search was performed in PubMed, Science Direct, and Scielo databases until December 27, 2021, based on criteria selected by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Statistical analysis was performed with Review Manager 5.4 software. The risk of bias was assessed using the Cochrane Risk of Bias Tool for Randomized Trials. A total of six studies containing 120 melasma patients treated with 5% cysteamine were included in this meta-analysis. The meta-analysis demonstrated that 5% cysteamine is effective for the treatment of patients with melasma (MD 6.26 [95% CI 3.68-8.83], p < 0.0001, I2  = 86%). In this review, through meta-analysis allows concluding that 5% cysteamine is effective in the treatment of melasma and presents a low probability of side or adverse effects.

Comparison of the efficacy of cysteamine 5% cream and hydroquinone 4%/ascorbic acid 3% combination cream in the treatment of epidermal melasma.

BACKGROUND: Few safe and effective treatments are available for melasma. Cysteamine, a non-melanocytotoxic molecule is a safer alternative to hydroquinone and usable for long-term use. AIM: To evaluate the effect of cysteamine 5% cream in the treatment of melasma. METHODS: Sixty-five of 80 patients completed this single-blind, randomized, controlled trial. The patients received cysteamine 5% or hydroquinone 4%/ascorbic acid 3% (HC) cream. The therapeutic response was evaluated by modified MASI (mMASI) and melanin index (SkinColorCatch) after 2 and 4 months of treatment. The effect of treatment on the quality of life was also assessed. RESULTS: The decrease in mMASI score was from 6.69 ± 2.96 to 4.47 ± 2.16 in the cysteamine group and from 6.26 ± 3.25 to 3.87 ± 2.00 in the HC group after 4 months (p values < 0.001). The melanin index decreased from 37.72 ± 10.17 to 31.47 ± 11.90 in the cysteamine group and from 36.37 ± 10.80 to 23.16 ± 8.83 in the HC group after 4 months (p-value = 0.003 and <0.001, respectively). The difference between mMASI score at baseline and month 4 was not significant between both groups (p-value > 0.05). The difference between the melanin index at baseline and month 4 was significantly more pronounced in the HC group (p-value = 0.002). Quality of life improved in both groups (p-value < 0.05), but was not significantly different between groups (p-value > 0.05). CONCLUSION: Cysteamine was confirmed to be an effective treatment for melasma, with equivalent results to HC in reducing mMASI score and improving quality of life, despite lesser melanin index reduction observed. Cysteamine and HC efficacy was confirmed in patients recalcitrant to previous treatments, by a significant reduction of mMASI and melanin index.

Transglutaminase 3 Attenuates Skin Inflammation in Psoriasis by Inhibiting NF-κB Activation through Phosphorylated STAT3-TET3 Signaling.

Transglutaminase 3 (TGM3) protects against skin inflammation in psoriasis, but the precise role and mechanism of action of TGM3 in the pathogenesis of psoriasis remain unclear. In this study, we show that TGM3 expression was increased in the skin lesions of patients with psoriasis and a mouse model of imiquimod-induced psoriatic dermatitis. TGM3 overexpression decreased the production of proinflammatory factors in cultured primary keratinocytes stimulated with psoriasis-related cytokines. TGM3 inhibited the phosphorylation of signal transducer and activator of transcription 3 and the recruitment of ten-eleven translocation 3 to the p65 gene promoter, resulting in decreased promoter demethylation and subsequent suppression of proinflammatory cytokine/chemokine production. TGM3-induced inhibition of phosphorylated p65 might also decrease ten-eleven translocation 3 expression. Moreover, topical application of Tgm3-specific small interfering RNA or the pan-transglutaminase inhibitor cysteamine exacerbated skin inflammation in mice with imiquimod-induced psoriatic dermatitis. Our study revealed an epigenetic pathway mediated by the interaction between TGM3 and ten-eleven translocation 3 in keratinocytes for regulation of skin inflammation in psoriasis, providing a potential target for psoriasis treatment.

A novel sustained-release cysteamine bitartrate formulation for the treatment of cystinosis: Pharmacokinetics and safety in healthy male volunteers.

The strict intake regimen of cysteamine bitartrate formulations, associated with side effects, is a concern for the treatment compliance in cystinosis therapy. Therefore, there is a need for a cysteamine formulation with an improved pharmacokinetic profile. This study investigated the pharmacokinetics, safety and tolerability of a new sustained-release cysteamine dosage form, PO-001, in healthy volunteers. This was a randomized, investigator-blinded, three-way cross-over study to compare single doses (600 mg) of PO-001 with Cystagon® (immediate-release) and Procysbi® (delayed-release). Collected blood samples were analyzed for plasma cysteamine concentrations and pharmacokinetic parameters were estimated by noncompartmental analysis. In addition, plasma cysteamine concentrations were analyzed using a population pharmacokinetic approach using NONMEM® . Pharmacokinetics showed clear sustained-release characteristics of PO-001 over time with a lower Cmax and longer Tmax compared to Cystagon® and Procysbi® . All treatment-emergent adverse events were of mild severity, with the exception of two subjects who reported moderate severity gastrointestinal problems including vomiting and diarrhea, which were related to Cystagon® intake. Population PK simulations showed a favourable PK profile based on Cmax and Ctrough concentrations at steady state. In conclusion, a single dose of 600 mg PO-001 was well tolerated with no findings of clinical concern. This new cysteamine bitartrate formulation showed pharmacokinetics of a sustained-release formulation, which may be beneficial for the treatment of cystinosis patients. This study supports advancing this type of sustained-release formulation into a subsequent study to confirm reduced dosing frequency with efficient control of white blood cells (WBCs) cystine levels. Netherlands Trial Registry (NTR) (NL67638.056.18).

Clinical evaluation of efficacy, safety and tolerability of cysteamine 5% cream in comparison with modified Kligman's formula in subjects with epidermal melasma: A randomized, double-blind clinical trial study.

BACKGROUND: Kligman's formula (KF) remains to date the dermatologists' treatment of choice for melasma. This study was aimed at the evaluation of the effectiveness of Modified Kligman's formula (MKF) in comparison with cysteamine 5% cream on the severity of epidermal melasma. MATERIALS AND METHODS: A total of 50 subjects with epidermal melasma were included in this double-blind, randomized trial study. Subjects received either cysteamine 5% cream or an MKF (4% hydroquinone, 0.05% retinoic acid and 0.1% betamethasone). Cysteamine cream (applied once daily, 15 minutes exposure) or MKF (applied once daily, whole night exposure) were used by the subjects over four consecutive months. The efficacy of the treatments was determined through the modified Melasma Area Severity Index (mMASI) score, the Investigator's Global Assessment (IGA) and patient questionnaires. RESULTS: The mean (SD) age of the subjects was 34.96 (6.17) and 35.76 (5.23) years for cysteamine and MKF group, respectively. The mean mMASI score after 4 months was 7.04 (2.23) in the MKF group and 6.09 (2.01) in the cysteamine group. At both prospective evaluation points (2 months, 4 months), the percentage reduction in mMASI score was approximately 9% greater by cysteamine cream as compared to MKF, and these differences were statistically significant (P = .005 and .001 respectively). CONCLUSION: Cysteamine 5% cream showed greater efficacy as compared to MKF. It is thus proposed that cysteamine 5% cream is more effective than MKF in the treatment of melasma, with the advantage of being significantly better tolerated.

Clinical evaluation of efficacy and tolerability of cysteamine 5% cream in comparison with tranexamic acid mesotherapy in subjects with melasma: a single-blind, randomized clinical trial study.

This study was aimed at evaluating the efficacy of Tranexamic Acid (TA) mesotherapy versus cysteamine 5% cream in the treatment of melasma. This single-blind, randomized clinical trial was conducted among 54 subjects between 2018 and 2019. Cysteamine 5% cream group was instructed to apply the cream on the melasma lesions 30 min before bed for 4 consecutive months. Conversely, 0.05 mL (4 mg/mL) TA mesotherapy was performed by a physician every 4 weeks until 2 months. The severity of melasma was evaluated using both Dermacatch® device and the modified Melasma Area Severity Index (mMASI). The most remarkable improvement rate was observed in the TA group at the third visit based on mMASI and Dermacatch® values at 47% and 15% in turn. The mMASI scores were substantially improved in both groups at the second visit (cysteamine vs TA 8.48 ± 2.34 and 7.03 ± 3.19; P = 0.359) and third visit (cysteamine vs TA 6.32 ± 2.11 and 5.52 ± 2.55; P = 0.952) as compared to baseline (cysteamine vs TA: 11.68 ± 2.70 and 10.43 ± 2.69). Dermacatch® values were significantly declined at the second and third visits (cysteamine vs TA 42.54 ± 12.84 and 38.75 ± 9.80, P = 0.365; 40.74 ± 12.61 and 36.17 ± 10.3, P = 0.123, respectively) compared with baseline (cysteamine vs TA 45.76 ± 13.41 and 42.41 ± 10.48), although the improvement rates between two groups were not significantly different. Findings suggest that none of the cysteamine and TA mesotherapy treatments measured by both mMASI and Dermacatch® methods have substantial advantages over the other; however, complications are less in the cysteamine than the TA mesotherapy group.

Oral cysteamine as an adjunct treatment in cystic fibrosis pulmonary exacerbations: An exploratory randomized clinical trial.

BACKGROUND: Emerging data suggests a possible role for cysteamine as an adjunct treatment for pulmonary exacerbations of cystic fibrosis (CF) that continue to be a major clinical challenge. There are no studies investigating the use of cysteamine in pulmonary exacerbations of CF. This exploratory randomized clinical trial was conducted to answer the question: In future pivotal trials of cysteamine as an adjunct treatment in pulmonary exacerbations of CF, which candidate cysteamine dosing regimens should be tested and which are the most appropriate, clinically meaningful outcome measures to employ as endpoints? METHODS AND FINDINGS: Multicentre double-blind randomized clinical trial. Adults experiencing a pulmonary exacerbation of CF being treated with standard care that included aminoglycoside therapy were randomized equally to a concomitant 14-day course of placebo, or one of 5 dosing regimens of cysteamine. Outcomes were recorded on days 0, 7, 14 and 21 and included sputum bacterial load and the patient reported outcome measures (PROMs): Chronic Respiratory Infection Symptom Score (CRISS), the Cystic Fibrosis Questionnaire-Revised (CFQ-R); FEV1, blood leukocyte count, and inflammatory markers. Eighty nine participants in fifteen US and EU centres were randomized, 78 completed the 14-day treatment period. Cysteamine had no significant effect on sputum bacterial load, however technical difficulties limited interpretation. The most consistent findings were for cysteamine 450mg twice daily that had effects additional to that observed with placebo, with improved symptoms, CRISS additional 9.85 points (95% CI 0.02, 19.7) p = 0.05, reduced blood leukocyte count by 2.46x109 /l (95% CI 0.11, 4.80), p = 0.041 and reduced CRP by geometric mean 2.57 nmol/l (95% CI 0.15, 0.99), p = 0.049. CONCLUSION: In this exploratory study cysteamine appeared to be safe and well-tolerated. Future pivotal trials investigating the utility of cysteamine in pulmonary exacerbations of CF need to include the cysteamine 450mg doses and CRISS and blood leukocyte count as outcome measures. CLINICAL TRIAL REGISTRATION: NCT03000348; www.clinicaltrials.gov.

A comparative study of topical 5% cysteamine versus 4% hydroquinone in the treatment of facial melasma in women.

OBJECTIVE: To assess the efficacy and safety of topical 5% cysteamine versus 4% hydroquinone in the treatment of facial melasma in women. Topical 5% cysteamine is an antioxidant and tyrosinase inhibitor that has been shown to be effective in the treatment of melasma. However, to date, no study has compared the performance of topical cysteamine to hydroquinone for facial melasma. METHODS: A quasi-randomized, multicenter, evaluator-blinded clinical trial was conducted on 40 women with facial melasma who were submitted to the nightly application of 5% cysteamine (CYS) or 4% hydroquinone (HQ) on hyperpigmented areas for 120 days. Both groups were required to use tinted sunscreen (SPF 50; PPD 19). Subjects were assessed at the inclusion and after 60 and 120 days of treatment for mMASI, MELASQoL, and the difference in colorimetric luminosity between melasma and the adjacent unaffected skin. The Global Aesthetic Improvement Scale was used to assess the difference in the appearance of the skin through standardized photographs. RESULTS: The mean reduction of the mMASI scores was 24% for CYS and 41% for HQ (P = 0.015) at 60 days, and 38% for CYS and 53% for HQ (P = 0.017) at 120 days. The photographic evaluation revealed up to 74% improvement for both groups, without statistically significant difference between them (P = 0.087). The MELASQoL score showed a progressive decrease for both groups over time, despite the greater reduction for HQ after 120 days (P = 0.018). Colorimetric assessment disclosed progressive depigmenting in both groups, without statistically significant difference between them (P > 0.160). No severe adverse effects were identified in either group. Erythema and burning were the most important local adverse effects with cysteamine, although their frequency did not differ between groups (P > 0.170). CONCLUSION: Cysteamine proved to be safe, well-tolerated, and effective, despite its inferior performance to hydroquinone in decreasing mMASI and MELASQoL in the treatment of melasma.

Effects of long-term cysteamine treatment in patients with cystinosis.

Cystinosis is a rare autosomal-recessive lysosomal storage disease with high morbidity and mortality. It is caused by mutations in the CTNS gene that encodes the cystine transporter, cystinosin, which leads to lysosomal cystine accumulation. Patients with infantile nephropathic cystinosis, the most common and most severe clinical form of cystinosis, commonly present with renal Fanconi syndrome by 6-12 months of age, and without specific treatment, almost all will develop end-stage renal disease (ESRD) by 10-12 years of age. Early corneal cystine crystal deposition is a hallmark of the disease. Cystinosis also presents with gastrointestinal symptoms (e.g., vomiting, decreased appetite, and feeding difficulties) and severe growth retardation and may affect several other organs over time, including the eye, thyroid gland, gonads, pancreas, muscles, bone marrow, liver, nervous system, lungs, and bones. Cystine-depleting therapy with cysteamine orally is the only specific targeted therapy available for managing cystinosis and needs to be combined with cysteamine eye drops for corneal disease involvement. In patients with early treatment initiation and good compliance to therapy, long-term cysteamine treatment delays progression to ESRD, significantly improves growth, decreases the frequency and severity of extrarenal complications, and is associated with extended life expectancy. Therefore, early diagnosis of cystinosis and adequate life-long treatment with cysteamine are essential for preventing end-organ damage and improving the overall prognosis in these patients.

Pharmacological application of barium containing bioactive glass in gastro-duodenal ulcers.

Peptic ulcer is prevalent in about 4% of the world population and nearly 10% of people have been affected by peptic ulcer at some point in their life. Therefore, there is a need for newer efficient and safe anti-ulcer agents. In the present strategy, we have prepared a novel bioactive glass containing 1.3 mol% of barium oxide (BaBG) and evaluated its antiulcer potential in gastroduodenal ulcer models. Prophylactic effect of BaBG pretreatment was evaluated for 5 days in ethanol, aspirin and pyloric ligation-induced gastric ulcer and cysteamine-induced duodenal ulcer models. Repeated treatment of 10 days of BaBG was evaluated in the healing ulcer model of acetic acid. BaBG significantly reduced the ulcerative damage against all the five tested ulcer models. Scanning electron microscope (SEM) images have shown that BaBG forms a physical protective barrier over the gastro-duodenal epithelium cell. In the pyloric-ligation, ethanol and aspirin models, BaBG showed significantly increased in gastric pH, indicating antacid like activity. BaBG treatment significantly increased cell proliferation in the pyloric model. Thus, BaBG mediates antiulcer action by forming a protective physical barrier against harsh luminal factors, acid neutralization and cell proliferation.

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.

BACKGROUND: 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 Dermacatch® (72.3 ± 27.8 and 52.9 ± 16.4, respectively) and Mexameter® (93.6 ± 42.6 and 65.4 ± 22.6, respectively). At 2 months, the mean differences were 38.1 ± 15.3 (Dermacatch®) and 49.9 ± 19 (Mexameter®) in the cysteamine group and 64.9 ± 25.3 (Dermacatch®) and 68 ± 26.2 (Mexameter®) in the placebo group. At 4 months, the mean differences were 23.8 ± 12.9 (Dermacatch®) and 35.5 ± 16.1 (Mexameter®) in the cysteamine group, and 50 ± 18 (Dermacatch®) and 51.2 ± 16.8 (Mexameter®) in the placebo group. Statistically significant differences were found between the cysteamine and placebo group outcomes at both time points (p = .01, p = .02). At the end of the treatment period, MASI scores were significantly lower in the cysteamine group versus placebo (8.03 ± 5.2 vs. 12.2 ± 7.4, p = .04). IGA scores and patient viewpoints indicated significant efficacy of cysteamine cream versus placebo. CONCLUSION: Cysteamine cream showed significant efficacy in decreasing melanin content of the lesions, as established by Dermacatch® as a new measuring method.

A randomized, double-blind, placebo-controlled trial evaluating cysteamine in Huntington's disease.

BACKGROUND: Cysteamine has been demonstrated as potentially effective in numerous animal models of Huntington's disease. METHODS: Ninety-six patients with early-stage Huntington's disease were randomized to 1200 mg delayed-release cysteamine bitartrate or placebo daily for 18 months. The primary end point was the change from baseline in the UHDRS Total Motor Score. A linear mixed-effects model for repeated measures was used to assess treatment effect, expressed as the least-squares mean difference of cysteamine minus placebo, with negative values indicating less deterioration relative to placebo. RESULTS: At 18 months, the treatment effect was not statistically significant - least-squares mean difference, -1.5 ± 1.71 (P = 0.385) - although this did represent less mean deterioration from baseline for the treated group relative to placebo. Treatment with cysteamine was safe and well tolerated. CONCLUSIONS: Efficacy of cysteamine was not demonstrated in this study population of patients with Huntington's disease. Post hoc analyses indicate the need for definitive future studies. © 2017 International Parkinson and Movement Disorder Society.

Cysteamine supplementation revealed detrimental effect on cryosurvival of buffalo sperm based on computer-assisted semen analysis and oxidative parameters.

The aim of this study was to investigate the effect of addition of cysteamine to the semen extender on post-thaw semen quality. A total of 30 ejaculates were collected from six bulls. Each ejaculate was divided into five equal parts and diluted to final concentration of 80 million sperms/mL using Optixcell®(IMV, France) semen extender supplemented with different concentrations of cysteamine (0, 0.75, 1.25, 2.5 and 5mM) and cryopreserved. In the frozen-thawed samples, the VAP, VSL, VCL ALH and sperm motility of control samples was greater (P<0.05) than cysteamine treated samples. The sperm abnormality and malondialdehyde (MDA) concentration were found highest in 5mM cysteamine treated samples. The cysteamine treated samples travelled significantly less distance in cervical mucus as compared to control. Further, cysteamine decreased acrosomal integrity of sperm. In incubation test, control samples showed better sperm motility as compared to treatment groups. Further, cysteamine supplementation decreased the total antioxidants and increased the MDA concentration of sperm. From the study, we hypothesized that cysteamine cannot stimulate synthesis of glutathione (GSH) intracellularly in sperm to combat free radicals because during the maturation, sperm lost its cytoplasm which is necessary for biochemical reaction in which cysteamine reacts with cystine to form a mixed disulfide which taken up by cells and split into cysteine in the cytoplasm. Synthesis of GSH depends on the availability of cysteine. In conclusion, the results of our study strongly emphasize that cysteamine would not be a suitable additive in extender for freezing buffalo bull semen.