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 The Cardioprotective Actions of Hydrogen Sulfide in Acute Myocardial Infarction and Heart Failure

Scientifica ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
David J. Polhemus ◽  
John W. Calvert ◽  
Javed Butler ◽  
David J. Lefer
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Hydrogen Sulfide ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Multiple Organ ◽  
Organ Systems ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

It has now become universally accepted that hydrogen sulfide (H2S), previously considered only as a lethal toxin, has robust cytoprotective actions in multiple organ systems. The diverse signaling profile of H2S impacts multiple pathways to exert cytoprotective actions in a number of pathological states. This paper will review the recently described cardioprotective actions of hydrogen sulfide in both myocardial ischemia/reperfusion injury and congestive heart failure.

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.

Considerations for Hand Surgery in Patients With Scleroderma

Hand ◽  
2021 ◽  
pp. 155894472110172
Author(s):  
Chelsea R. Brown ◽  
Nisha J. Crouser ◽  
Amy L. Speeckaert
Keyword(s):  
Systemic Sclerosis ◽  
Hand Function ◽  
Treatment Strategies ◽  
Hand Surgery ◽  
Multiple Organ ◽  
Surgical Patients ◽  
Raynaud Phenomenon ◽  
Joint Contractures ◽  
Hand Surgeon ◽  
Organ Systems

Systemic sclerosis (scleroderma, SSc) is an autoimmune disease that causes significant dysfunction to multiple organ systems, including the musculoskeletal system. It poses significant challenges to the hand surgeon, including calcinosis, ischemic changes, Raynaud phenomenon, tendinopathies, synovitis, and joint contractures. Patients with SSc also suffer from multiorgan dysfunction, which makes them high-risk surgical patients. The hand surgeon must understand the pathophysiology, treatment strategies, and special operative considerations required in this population to avoid complications and help maintain or improve hand function.

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 EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR)

2009 ◽  
Vol 68 (5) ◽  
pp. 620-628 ◽  
Author(s):  
O Kowal-Bielecka ◽  
R Landewé ◽  
J Avouac ◽  
S Chwiesko ◽  
I Miniati ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Clinical Research ◽  
Research Group ◽  
Task Force ◽  
Multiple Organ ◽  
Future Research ◽  
Scleroderma Renal Crisis ◽  
Evidence Based ◽  
Future Research Agenda ◽  
Organ Systems

Purpose:The optimal treatment of systemic sclerosis (SSc) is a challenge because the pathogenesis of SSc is unclear and it is an uncommon and clinically heterogeneous disease affecting multiple organ systems. The aim of the European League Against Rheumatism (EULAR) Scleroderma Trials and Research group (EUSTAR) was to develop evidence-based, consensus-derived recommendations for the treatment of SSc.Methods:To obtain and maintain a high level of intrinsic quality and comparability of this approach, EULAR standard operating procedures were followed. The task force comprised 18 SSc experts from Europe, the USA and Japan, two SSc patients and three fellows for literature research. The preliminary set of research questions concerning SSc treatment was provided by 74 EUSTAR centres.Results:Based on discussion of the clinical research evidence from published literature, and combining this with current expert opinion and clinical experience, 14 recommendations for the treatment of SSc were formulated. The final set includes the following recommendations: three on SSc-related digital vasculopathy (Raynaud’s phenomenon and ulcers); four on SSc-related pulmonary arterial hypertension; three on SSc-related gastrointestinal involvement; two on scleroderma renal crisis; one on SSc-related interstitial lung disease and one on skin involvement. Experts also formulated several questions for a future research agenda.Conclusions:Evidence-based, consensus-derived recommendations are useful for rheumatologists to help guide treatment for patients with SSc. These recommendations may also help to define directions for future clinical research in SSc.

Cardiovascular physiology teaching: computer simulations vs. animal demonstrations.

1994 ◽  
Vol 266 (6) ◽  
pp. S36 ◽  
Author(s):  
R W Samsel ◽  
G A Schmidt ◽  
J B Hall ◽  
L D Wood ◽  
S G Shroff ◽  
...  
Keyword(s):  
Conceptual Knowledge ◽  
Animal Studies ◽  
Computer Software ◽  
Cost Effective ◽  
Multiple Organ ◽  
Cardiovascular Physiology ◽  
Laboratory Observation ◽  
Organ Systems ◽  
Laboratory Tool

The roots of physiology lie in laboratory observation, and physiology courses continue to rely on laboratory observation to provide students with practical information to correlate with their developing base of conceptual knowledge. To this end, animal laboratories provide a functioning example of interactions among organ systems and a source of data for student analysis. However, there are continuing objections to using animals for teaching, and animal labs are costly in time and effort. As an alternative laboratory tool, computer software can simulate the operation of multiple organ systems: responses to interventions illustrate intrinsic organ behavior and integrated systems physiology. Advantages of software over animal studies include alteration of variables that are not easily changed in vivo, repeated interventions, and cost-effective hands-on student access. Nevertheless, simulations miss intangible aspects of experimental physiology, and results depend critically on the assumptions of the model. We used both computer and animal demonstrations in teaching cardiovascular physiology to first-year medical students. The students rated both highly, but the computer-based session received a higher rating. We believe that both forms of teaching have educational merit. At the introductory level, the computer appears to provide an effective alternative.

scholarly journals Vascular complications of cystathionine β-synthase deficiency: future directions for homocysteine-to-hydrogen sulfide research

2011 ◽  
Vol 300 (1) ◽  
pp. H13-H26 ◽  
Author(s):  
Richard S. Beard ◽  
Shawn E. Bearden
Keyword(s):  
Hydrogen Sulfide ◽  
Animal Studies ◽  
Disease Risk ◽  
Vascular Complications ◽  
Disease Risk Factor ◽  
Positive Effects ◽  
Relative Paucity ◽  
Transsulfuration Pathway ◽  
Rate Limiting

Homocysteine (Hcy), a cardiovascular and neurovascular disease risk factor, is converted to hydrogen sulfide (H2S) through the transsulfuration pathway. H2S has attracted considerable attention in recent years for many positive effects on vascular health and homeostasis. Cystathionine β-synthase (CBS) is the first, and rate-limiting, enzyme in the transsulfuration pathway. Mutations in the CBS gene decrease enzymatic activity, which increases the plasma Hcy concentration, a condition called hyperhomocysteinemia (HHcy). Animal models of CBS deficiency have provided invaluable insights into the pathological effects of transsulfuration impairment and of both mild and severe HHcy. However, studies have also highlighted the complexity of HHcy and the need to explore the specific details of Hcy metabolism in addition to Hcy levels per se. There has been a relative paucity of work addressing the dysfunctional H2S production in CBS deficiency that may contribute to, or even create, HHcy-associated pathologies. Experiments using CBS knockout mice, both homozygous (−/−) and heterozygous (+/−), have provided 15 years of new knowledge and are the focus of this review. These murine models present the opportunity to study a specific mechanism for HHcy that matches one of the etiologies in many human patients. Therefore, the goal of this review was to integrate and highlight the critical information gained thus far from models of CBS deficiency and draw attention to critical gaps in knowledge, with particular emphasis on the modulation of H2S metabolism. We include findings from human and animal studies to identify important opportunities for future investigation that should be aimed at generating new basic and clinical understanding of the role of CBS and transsulfuration in cardiovascular and neurovascular disease.

Microprobe analysis of inclusion bodies related to two benzofuran derivatives

1987 ◽  
Vol 45 ◽  
pp. 672-673
Author(s):  
T. L. Benning ◽  
P. Ingram ◽  
J. D. Shelburne
Keyword(s):  
Inclusion Bodies ◽  
Uranyl Acetate ◽  
Multiple Organ ◽  
High Dose ◽  
En Bloc ◽  
Tissue Samples ◽  
Transmission Electron ◽  
Organ Systems ◽  
Dense Inclusion ◽  
Melanin Complex

Two benzofuran derivatives, chlorpromazine and amiodarone, are known to produce inclusion bodies in human tissues. Prolonged high dose chlorpromazine therapy causes hyperpigmentation of the skin with electron-dense inclusion bodies present in dermal histiocytes and endothelial cells ultrastructurally. The nature of the deposits is not known although a drug-melanin complex has been hypothesized. Amiodarone may also cause cutaneous hyperpigmentation and lamellar lysosomal inclusion bodies have been demonstrated within the cells of multiple organ systems. These lamellar bodies are believed to be the product of an amiodarone-induced phospholipid storage disorder. We performed transmission electron microscopy (TEM) and energy dispersive x-ray microanalysis (EDXA) on tissue samples from patients treated with these drugs, attempting to detect the sulfur atom of chlorpromazine and the iodine atom of amiodarone within their respective inclusion bodies.A skin biopsy from a patient with hyperpigmentation due to prolonged chlorpromazine therapy was fixed in 4% glutaraldehyde and processed without osmium tetroxide or en bloc uranyl acetate for Epon embedding.

Impairment Rating and Spinal Cord Injuries: Revisiting the Guides

2010 ◽  
Vol 15 (3) ◽  
pp. 1-7
Author(s):  
Richard T. Katz
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
Functional Independence ◽  
Outcome Data ◽  
Multiple Organ ◽  
Loss Of Function ◽  
Sixth Edition ◽  
Organ Systems ◽  
Cord Injury ◽  
Impairment Ratings

Abstract This article addresses some criticisms of the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides) by comparing previously published outcome data from a group of complete spinal cord injury (SCI) persons with impairment ratings for a corresponding level of injury calculated using the AMA Guides, Sixth Edition. Results of the comparison show that impairment ratings using the sixth edition scale poorly with the level of impairments of activities of daily living (ADL) in SCI patients as assessed by the Functional Independence Measure (FIM) motor scale and the extended FIM motor scale. Because of the combinations of multiple impairments, the AMA Guides potentially overrates the impairment of paraplegics compared with that of quadriplegics. The use and applicability of the Combined Values formula should be further investigated, and complete loss of function of two upper extremities seems consistent with levels of quadriplegia using the SCI model. Some aspects of the AMA Guides contain inconsistencies. The concept of diminishing impairment values is not easily translated between specific losses of function per organ system and “overall” loss of ADLs involving multiple organ systems, and the notion of “catastrophic thresholds” involving multiple organ systems may support the understanding that variations in rating may exist in higher rating cases such as those that involve an SCI.

Renal Manifestations of Tuberous Sclerosis Complex

2020 ◽  
Vol 7 (3) ◽  
pp. 5-19
Author(s):  
Nikhil Nair ◽  
Ronith Chakraborty ◽  
Zubin Mahajan ◽  
Aditya Sharma ◽  
Sidarth Sethi ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Gene Disruption ◽  
Treatment Guidelines ◽  
Renal Cysts ◽  
Skin Lesions ◽  
Multiple Organ ◽  
Tsc2 Gene ◽  
Genetic Condition ◽  
Organ Systems

Tuberous sclerosis complex (TSC) is a genetic condition caused by a mutation in either the TSC1 or TSC2 gene. Disruption of either of these genes leads to impaired production of hamartin or tuberin proteins, leading to the manifestation of skin lesions, tumors and seizures. TSC can manifests in multiple organ systems with the cutaneous and renal systems being the most commonly affected. These manifestations can secondarily lead to the development of hypertension, chronic kidney disease, and neurocognitive declines. The renal pathologies most commonly seen in TSC are angiomyolipoma, renal cysts and less commonly, oncocytomas. In this review, we highlight the current understanding on the renal manifestations of TSC along with current diagnosis and treatment guidelines.

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