Pulmonary artery hypertension (PAH) is marked by proliferation of vasculature and remodeling of small pulmonary arteries which causes an increase in pulmonary vascular resistance. The resultant pulmonary artery hypertension can lead to right heart failure and death. Both endothelial and smooth muscle cells appear to play a role in the development and progression of PAH. The underlying cause of most cases of PAH is unknown, but some cases are associated with autoimmune diseases such as scleroderma or systemic sclerosis. PAH is also a complication of chronic lung diseases such as chronic bronchitis and emphysema and interstitial lung diseases such as sarcoidosis. Agents used for PAH, however, are largely effective in patients with idiopathic forms of this condition who do not have major structural damage to the lungs (secondary PAH). Pharmacotherapy of PAH has recently advanced with the development of specific antagonists and inhibitors of receptors and pathways involved in the modulation of smooth muscle tone in the pulmonary vasculature. Three major classes of agents are used: prostaglandins, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors. Prostacyclin is a prostaglandin that is produced by endothelial cells in the lungs and directly relaxes the smooth muscle cells in the pulmonary vasculature. In idiopathic PAH, there is reduced production of prostacyclin. Stable analogues of prostacyclin have been developed which can be given by infusion or inhalation and result in temporary decrease in pulmonary artery pressure.

Penicillamine is chelating agent used to decrease copper stores in Wilson disease, which also has immunomodulatory activity in rheumatic diseases such as rheumatoid arthritis, scleroderma and systemic lupus erythematosus. Penicillamine is capable of causing hypersensitivity reactions, some of which are accompanied by liver injury which is typically cholestatic.

In systemic sclerosis (SSc), the use of corticosteroids (CS) is controversial due to their association with scleroderma renal crisis (SRC). However, patients with very early and early disease, characterised by main inflammatory component, may benefit from CS therapy. The aim of this review is to discuss pros and cons of CS treatment in SSc, providing current evidence about the use of CS in SSc. Moreover, we discuss also the underlying pathogenetic mechanisms that may be the background for the potential harms and efficacy of CS in SSc.

Fibrosis is the abnormal deposition of extracellular matrix, which can lead to organ dysfunction, morbidity, and death. The disease burden caused by fibrosis is substantial, and there are currently no therapies that can prevent or reverse fibrosis. Metabolic alterations are increasingly recognized as an important pathogenic process that underlies fibrosis across many organ types. As a result, metabolically targeted therapies could become important strategies for fibrosis reduction. Indeed, some of the pathways targeted by antifibrotic drugs in development - such as the activation of transforming growth factor-β and the deposition of extracellular matrix - have metabolic implications. This Review summarizes the evidence to date and describes novel opportunities for the discovery and development of drugs for metabolic reprogramming, their associated challenges, and their utility in reducing fibrosis. Fibrotic therapies are potentially relevant to numerous common diseases such as cirrhosis, non-alcoholic steatohepatitis, chronic renal disease, heart failure, diabetes, idiopathic pulmonary fibrosis, and scleroderma.

Glutathione transferase P1-1 (GSTP1-1) is expressed in some human tissues and is abundant in mammalian erythrocytes (here termed e-GST). This enzyme is able to detoxify the cell from endogenous and exogenous toxic compounds by using glutathione (GSH) or by acting as a ligandin. This review collects studies that propose GSTP1-1 as a useful biomarker in different fields of application. The most relevant studies are focused on GSTP1-1 as a biosensor to detect blood toxicity in patients affected by kidney diseases. In fact, this detoxifying enzyme is over-expressed in erythrocytes when unusual amounts of toxins are present in the body. Here we review articles concerning the level of GST in chronic kidney disease patients, in maintenance hemodialysis patients and to assess dialysis adequacy. GST is also over-expressed in autoimmune disease like scleroderma, and in kidney transplant patients and it may be used to check the efficiency of transplanted kidneys. The involvement of GSTP in the oxidative stress and in other human pathologies like cancer, liver and neurodegenerative diseases, and psychiatric disorders is also reported. Promising applications of e-GST discussed in the present review are its use for monitoring human subjects living in polluted areas and mammals for veterinary purpose.