scholarly journals Correction: Abdulle, A.E., et al. Hydrogen Sulfide: A Therapeutic Option in Systemic Sclerosis. Int. J. Mol. Sci. 2018, 19, 4121

2019 ◽  
Vol 20 (22) ◽  
pp. 5663
Author(s):  
Amaal Eman Abdulle ◽  
Harry van Goor ◽  
Douwe J. Mulder
Keyword(s):  
Hydrogen Sulfide ◽  
Systemic Sclerosis ◽  
Therapeutic Option

The authors wish to make the following correction to this paper [...]

scholarly journals Hydrogen Sulfide: A Therapeutic Option in Systemic Sclerosis

2018 ◽  
Vol 19 (12) ◽  
pp. 4121 ◽  
Author(s):  
Amaal Abdulle ◽  
Harry van Goor ◽  
Douwe Mulder
Keyword(s):  
Hydrogen Sulfide ◽  
Systemic Sclerosis ◽  
Animal Studies ◽  
Therapeutic Option ◽  
Multiple Organ ◽  
Current Data ◽  
Organ Systems ◽  
Transsulfuration Pathway ◽  
Exact Etiology ◽  
Vascular Physiology

Systemic sclerosis (SSc) is a lethal disease that is characterized by auto-immunity, vascular injury, and progressive fibrosis of multiple organ systems. Despite the fact that the exact etiology of SSc remains unknown, oxidative stress has been associated with a large range of SSc-related complications. In addition to the well-known detrimental properties of reactive oxygen species (ROS), gasotransmitters (e.g., nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S)) are also thought to play an important role in SSc. Accordingly, the diverse physiologic actions of NO and CO and their role in SSc have been previously studied. Recently, multiple studies have also shown the importance of the third gasotransmitter H2S in both vascular physiology and pathophysiology. Interestingly, homocysteine (which is converted into H2S through the transsulfuration pathway) is often found to be elevated in SSc patients; suggesting defects in the transsulfuration pathway. Hydrogen sulfide, which is known to have several effects, including a strong antioxidant and vasodilator effect, could potentially play a prominent role in the initiation and progression of vasculopathy. A better understanding of the actions of gasotransmitters, like H2S, in the development of SSc-related vasculopathy, could help to create early interventions to attenuate the disease course. This paper will review the role of H2S in vascular (patho-)physiology and potential disturbances in SSc. Moreover, current data from experimental animal studies will be reviewed. Lastly, we will evaluate potential interventional strategies.

scholarly journals A 3-Year Observational Study of Patients with Progressive Systemic Sclerosis Treated with an Intensified B Lymphocyte Depletion Protocol: Clinical and Immunological Response

2021 ◽  
Vol 10 (2) ◽  
pp. 292
Author(s):  
Daniela Rossi ◽  
Savino Sciascia ◽  
Irene Cecchi ◽  
Marta Saracco ◽  
Erika Montabone ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Topoisomerase I ◽  
B Lymphocyte ◽  
Therapeutic Option ◽  
Oral Prednisone ◽  
Progressive Systemic Sclerosis ◽  
Severe Infection ◽  
Forced Expiratory Volume ◽  
Respiratory Impairment ◽  
Mean Values

Background: B-cells have been suggested to play a role in the pathogenesis of systemic sclerosis (SSc), representing, therefore, a potential therapeutic target. Objectives: We aimed at investigating the 36-month outcomes of 20 SSc patients who underwent an intensified B-depletion therapy (IBCDT) scheme, including both Rituximab (RTX) and cyclophosphamide (CYC). Methods: Data from 20 severe patients (18 females and 2 males, mean age 66.7 ± 11.0 years) with diffuse SSc (anti-topoisomerase I antibody in 95%) patients with multiorgan involvement including interstitial lung disease (ILD) treated with an IBCDT were prospectively collected. IBCDT comprehended: RTX 375 mg/m2 administered for four weekly doses (on days 1, 8, 15, and 22), followed by two additional doses after 30 and 60 days, in addition to two administrations of 10 mg/kg of intravenous CYC plus three methylprednisolone pulses (15 mg/kg) and subsequently followed by oral prednisone rapidly tapered to low minimum dosage of 5 mg daily. In addition, 10 patients with more severe functional respiratory impairment at baseline were also treated with RTX 500 mg every 4 months during the first year and two times a year during the second and the third year. Results: After 36 months of follow-up, we recorded significant amelioration in N-terminal-pro-brain natriuretic peptide (NT-proBNP) levels (mean 385.4 ± 517 pg/mL at baseline to 279 ± 543 after 36 months). In addition, a significant radiological improvement of ILD in 20% of patients (4/20) and a radiological stabilization with no sign of progression of interstitial involvement in 13/20 (65%) were documented. A total of 3 out of 20 (15%) patients experienced a worsening of the ILD. No patient showed further decrease in functional respiratory parameters, including forced vital capacity, forced expiratory volume in one second, and mean values of diffusing capacity for carbon monoxide Moreover, no patient showed any change in the ejection fraction and pulmonary artery pressure when comparing values at baseline and after 24 and 36 months of observation. No severe infection, renal flare, RTX-related side effects were observed. No patient died. Conclusions: Our findings support that the IBCDT was well tolerated and might be a promising therapeutic option for the management of SSc, especially in those subjects with multiorgan involvement that includes ILD.

Heart Transplantation in Systemic Sclerosis: A Therapeutic Option. Presentation of a Case and Literature Review

2021 ◽  
Author(s):  
Andrea de Diego-Sola ◽  
César A. Egües Dubuc ◽  
Cristina Goena Vives ◽  
Juan José Intxausti Irazabal ◽  
Olga Maíz Alonso ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Literature Review ◽  
Heart Transplantation ◽  
Therapeutic Option

Pharmacotherapy of Systemic Sclerosis: Focus on Bosentan

2009 ◽  
Vol 1 ◽  
pp. 1179559X0900100
Author(s):  
Kamyar Afshar ◽  
Ayana Boyd-King
Keyword(s):  
Quality Of Life ◽  
Pulmonary Hypertension ◽  
Systemic Sclerosis ◽  
Medical Management ◽  
Therapeutic Option ◽  
Organ Systems ◽  
Potent Vasoconstrictor ◽  
Clinical Worsening ◽  
Indications For Use

Systemic sclerosis is manifested by the massive deposition of collagen within various organ systems. Endothelin-1 has taken a pivotal role as not only a potent vasoconstrictor, but also as a profibrotic intermediary. Bosentan is proving to be a viable therapeutic option in alleviating manifestations of systemic sclerosis other than pulmonary hypertension. There are many reports in the literature profiling bosentan's safety, efficacy and tolerability in patients. In addition, it has greatly improved patients’ quality of life, reduced the number of hospitalizations and increased the time to clinical worsening of the disease. The clinical indications for use of bosentan in a wide array of patients has served as a valuable asset in the medical management of systemic sclerosis.

Mesenchymal stromal cells represent a therapeutic option for systemic sclerosis patients

2020 ◽  
Vol 27 ◽  
pp. 126-134
Author(s):  
Viviana Reyes-Martínez ◽  
John Londoño ◽  
Luz Mabel Ávila-Portillo ◽  
Juan Camilo Rueda ◽  
Diana Marcela Padilla-Ortiz ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Therapeutic Option

scholarly journals Is rituximab effective for systemic sclerosis? A systematic review and meta-analysis

2021 ◽  
Vol 61 (1) ◽  
Author(s):  
Marina Maria Vieira de Figueiredo Caldas ◽  
Kesley Pablo Morais de Azevedo ◽  
Ana Clara de França Nunes ◽  
Victor Hugo de Oliveira ◽  
Isac Davidson Santiago Fernandes Pimenta ◽  
...  
Keyword(s):  
Systematic Review ◽  
Systemic Sclerosis ◽  
Lung Disease ◽  
Therapeutic Option ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Risk Of Bias ◽  
Bibliographic Databases ◽  
Positive Effects ◽  
Manual Search

Abstract Background Systemic sclerosis (SSc) is a clinically complex and challenging disease, that leads to skin fibrosis. Its most frequent complication is interstitial lung disease (ILD), which leads to a worse prognosis. In this situation, cyclophosphamide is considered the gold standard for its treatment, despite the controversies regarding its efficacy and toxicity. However, studies using rituximab (RTX) have shown that this drug may be a promising therapeutic option. Objectives This paper objective was to analyze the scientific evidence on the RTX effects on SSc. Methods A systematic review (SR) was performed including clinical trials (CTs) on the use of RTX in SSc, published up to May 2020. The studies were identified through systematic searches in bibliographic databases using a predefined search strategy. The following databases were used: PUBMED, SCOPUS, SCIELO, LILACS, SCIENCE DIRECT, WEB OF SCIENCE, COCHRANE, WHOLIS, PAHO and EMBASE. Also, a manual search was performed. The methodological quality of the studies was determined using Jadad scale, Risk of Bias Tool (RoB 2.0) and Risk of Bias in Non-Randomized Studies - of Interventions tool (ROBINS-I). A meta-analysis of the randomized CTs was performed, using Review Manager. Results Ten CTs were included in this SR. Of these, three were randomized and seven were non-randomized. Five showed a statistically significant improvement in forced vital capacity (FVC) at some time during follow-up. Regarding the skin, eight studies showed statistically significant improvements according toa the modified Rodnan skin score. The meta-analysis found positive effects of RTX in SSc, with a statistical significance for lung disease. Conclusion Rituximab is a promising strategy for the SSc-associated ILD and cutaneous fibrosis treatment. PROSPERO registration number: CRD42019132018.

Innate immunity in systemic sclerosis pathogenesis

2013 ◽  
Vol 126 (5) ◽  
pp. 329-337 ◽  
Author(s):  
Steven O’Reilly
Keyword(s):  
Immune System ◽  
Systemic Sclerosis ◽  
Innate Immune System ◽  
Germ Line ◽  
Cell Damage ◽  
Therapeutic Option ◽  
Innate Immune ◽  
Lymphoid Cells ◽  
Low Grade ◽  
Matrix Deposition

The innate immune system is a critical part of the response to pathogens and overall immunity. Compared with the adaptive immune response, these innate responses are not antigen-specific and recognize patterns in bacteria, viruses and fungi. Chief among these are TLRs (Toll-like receptors). TLRs are PRRs (pattern recognition receptors) that are germ-line-encoded and are also able to recognize endogenous molecules that are released upon cell damage or stress and have been demonstrated to have a key role in numerous autoimmune diseases, including RA (rheumatoid arthritis) and SSc (systemic sclerosis). SSc is an autoimmune disorder in which vascular injury occurs and there is a chronic low-grade inflammation followed by excessive ECM (extracellular matrix) deposition and ultimately fibrosis. The fibrosis ultimately leads to organ dysfunction and death. The preceding vascular damage and activation of the innate immune system leads to mobilization of the innate lymphoid cells and the up-regulation of multiple genes and pro-fibrotic cytokines. These locally released cytokines activate resident fibroblasts to differentiate into myofibroblasts. The aim of the present review is to explore the role of the innate immune system in SSc and TLRs and how these interact with stromal cells to produce fibrosis. Targeting the innate immune system or specific components of the TLR signalling cascade may be a novel therapeutic option in what is an incurable disease.

scholarly journals Restoration of skeletal muscle homeostasis by hydrogen sulfide during hyperhomocysteinemia-mediated oxidative/ER stress condition

2019 ◽  
Vol 97 (6) ◽  
pp. 441-456 ◽  
Author(s):  
Avisek Majumder ◽  
Mahavir Singh ◽  
Akash K. George ◽  
Suresh C. Tyagi
Keyword(s):  
Skeletal Muscle ◽  
Hydrogen Sulfide ◽  
Er Stress ◽  
Stress Responses ◽  
Molecular Mechanisms ◽  
Therapeutic Option ◽  
Cellular Damage ◽  
Bidirectional Regulation ◽  
Muscle Homeostasis ◽  
Jnk Activation

Elevated homocysteine (Hcy), i.e., hyperhomocysteinemia (HHcy), causes skeletal muscle myopathy. Among many cellular and metabolic alterations caused by HHcy, oxidative and endoplasmic reticulum (ER) stress are considered the major ones; however, the precise molecular mechanism(s) in this process is unclear. Nevertheless, there is no treatment option available to treat HHcy-mediated muscle injury. Hydrogen sulfide (H2S) is increasingly recognized as a potent anti-oxidant, anti-apoptotic/necrotic/pyroptotic, and anti-inflammatory compound and also has been shown to improve angiogenesis during ischemic injury. Patients with CBS mutation produce less H2S, making them vulnerable to Hcy-mediated cellular damage. Many studies have reported bidirectional regulation of ER stress in apoptosis through JNK activation and concomitant attenuation of cell proliferation and protein synthesis via PI3K/AKT axis. Whether H2S mitigates these detrimental effects of HHcy on muscle remains unexplored. In this review, we discuss molecular mechanisms of HHcy-mediated oxidative/ER stress responses, apoptosis, angiogenesis, and atrophic changes in skeletal muscle and how H2S can restore skeletal muscle homeostasis during HHcy condition. This review also highlights the molecular mechanisms on how H2S could be developed as a clinically relevant therapeutic option for chronic conditions that are aggravated by HHcy.

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