dinoprost and Scleroderma--Systemic

Topics: Animals; Dinoprost; Humans; Hyperemia; Microcirculation; Oxidative Stress; Raynaud Disease; Scleroderma, Systemic; Skin

We report a case of systemic sclerosis (SSc) complicated with benign pneumoperitoneum without apparent pneumatosis cystoides intestinalis (PCI). A 43-year-old woman was admitted to our hospital because of prominent abdominal distension in April 1997. Raynaud's phenomenon has been detected since 1991. She was suffering from recurrent diarrhea, constipation, and subileus. The diagnosis of SSc was made in 1996 based on the sclerosis in her face, forearms, and chest, and hypomotility of the esophagus. On admission, she presented no signs of peritoneal irritation. The laboratory data revealed that white blood cell count was 7,400/mm3 and C-reactive protein was 0.1 mg/dl. Chest and abdominal roentgenograms showed massive free air under the diaphragm, dilatation of small and large intestine, and air-fluid level. PCI was not apparent. Pneumoperitoneum was improved after four weeks with intravenous hyperalimentation. But she presented recurrent severe diarrhea and high fever whenever she tried to take food orally. Klebsiella pneumoniae was proved in her jejunal juice by bacteriologic examination. Intravenous prostaglandin F2 alpha and oral fosfomycin calcium intake made her condition better. Benign pneumoperitoneum without PCI is rarely reported in the patients with SSc. In her condition, weakness of intestinal wall, hypomotility of intestine, unusual bacterial overgrowth, and elevated intraluminal pressure made intraluminal gas go through the wall of the fragile intestine of SSc. As operation of intestine of SSc usually cause miserable outcome, pneumoperitoneum accompanied with SSc even if PCI is apparent or not must be treated with conventional manner while there is no signs of peritoneal irritation.

Topics: Adult; Anti-Bacterial Agents; Dinoprost; Duodenum; Female; Fosfomycin; Humans; Klebsiella pneumoniae; Pneumatosis Cystoides Intestinalis; Pneumoperitoneum; Scleroderma, Systemic

Systemic sclerosis is a connective tissue disease in which oxidative stress represents an important player among the complex pathogenetic mechanisms of the disease. Iloprost, an analogue of natural prostacyclin, is used in systemic sclerosis for the treatment of severe Raynaud's phenomenon and ischemic ulcers. There is a clear evidence that iloprost attenuates oxidative damage induced by ischemia-reperfusion phenomena. The aim of this study is to evaluate the effect of iloprost on oxidative status in ten patients with systemic sclerosis by measuring urinary levels of 8-isoprostaglandin-F(2alpha), a member of F(2)-isoprostanes. We found that systemic sclerosis patients cyclically treated with iloprost showed increased urinary level of 8-isoprostaglandin-F(2alpha )in comparison with healthy subjects; urinary 8-isoprostaglandin-F(2alpha) did not diminish soon after the iloprost infusion as well as 3, 15 and 30 days after the drug administration. Unlike experimental studies, in vivo the strong vasodilator effect of iloprost infusion did not reduce oxidative status.

Topics: Dinoprost; Female; Humans; Iloprost; Infusions, Parenteral; Male; Middle Aged; Oxidative Stress; Scleroderma, Systemic; Time Factors; Treatment Outcome; Up-Regulation; Vasodilator Agents

The pathogenesis of scleroderma (SSc) includes components of autoimmunity, vascular dysfunction, and accumulation of extracellular matrix. 8-isoprostane, an oxidized lipid created by oxidative stress, activates the thromboxane A2 receptor (TXAR) and the Rho-associated kinase (ROCK) pathway. In this study, we determined whether the TXAR was activated by 8-isoprostane in SSc endothelial cells (ECs) and whether this pathway inhibited VEGF-induced angiogenesis. Elevated 8-isoprostane was observed in plasma and conditioned media from SSc patients. SSc-conditioned media inhibited EC tube formation, whereas addition of vitamin E, by reducing 8-isoprostane, increased tube formation. VEGF did not induce angiogenesis in SSc ECs, but vitamin E or TXAR inhibition restored its effect. The expression of TXAR, RhoA, and ROCK1/2 was elevated in SSc ECs. ROCK activity and 8-isoprostane-induced ROCK activation were significantly higher in SSc ECs, whereas VEGF had no effect. The hyper-activation of the TXAR leads to inhibition of VEGF-induced angiogenesis, as inhibition of the TXAR pathway results in a blockade of 8-isoprostane-induced ROCK activation and restoration of VEGF activity. These results suggest that the TXAR pathway has a crucial role in angiogenesis and that 8-isoprostane is not just a by-product of oxidative stress but also has a significant role in the impaired angiogenesis that characterizes SSc.

Topics: Adult; Collagen; Dinoprost; Drug Combinations; Endothelial Cells; Female; Focal Adhesion Protein-Tyrosine Kinases; Humans; Laminin; Male; Middle Aged; Neovascularization, Physiologic; Oxidative Stress; Phosphorylation; Proteoglycans; Receptors, Thromboxane A2, Prostaglandin H2; rho-Associated Kinases; Scleroderma, Systemic; Vascular Endothelial Growth Factor A

Systemic sclerosis (SSc) is characterized by fibrosis of the skin and visceral organs. Patients with SSc have enhanced plasma levels of the plasmin-α2-antiplasmin (α2AP) complex, and we recently implicated α2AP in the development of fibrosis through transforming growth factor β (TGFβ) production. This study was undertaken to clarify how α2AP induces TGFβ production and the development of fibrosis.. To clarify the detailed mechanism by which α2AP induces TGFβ production, we focused on adipose triglyceride lipase (ATGL)/calcium-independent phospholipase A(2) (iPLA(2)) and examined whether ATGL/ iPLA(2) is associated with α2AP-induced TGFβ production. The mouse model of bleomycin-induced SSc was used to evaluate the role of α2AP in the development of fibrosis. Dermal thickness and collagen content were determined in mouse skin treated with phosphate buffered saline or bleomycin. Moreover, we cultured SSc-like fibroblasts from the bleomycin-treated mouse skin and examined the production of TGFβ and prostaglandin F(2α) (PGF(2α)).. We found that α2AP binding to ATGL promoted PGF(2α) synthesis through iPLA(2) in fibroblasts, and the PGF(2α) synthesis that was promoted by α2AP induced TGFβ production in fibroblasts. In addition, the neutralization of α2AP attenuated the production of TGFβ and PGF(2α) in SSc-like fibroblasts from mice. The α2AP deficiency attenuated bleomycin-induced fibrosis and PGF(2α) synthesis, while the administration of PGF(2α) to α2AP-deficient mice facilitated α2AP deficiency-attenuated fibrosis.. These findings suggest that α2AP regulates the development of fibrosis by PGF(2α) synthesis through ATGL/iPLA(2). The inhibition of α2AP-initiated pathways might provide a novel therapeutic approach to fibrotic diseases.

Topics: alpha-2-Antiplasmin; Animals; Bleomycin; Cells, Cultured; Collagen; Dinoprost; Dinoprostone; Disease Models, Animal; Fibroblasts; Fibrosis; Lipase; Mice; Phospholipases A2, Calcium-Independent; Scleroderma, Systemic; Signal Transduction; Skin; Transforming Growth Factor beta

The objective of the study was to determine the presence or levels of antibodies (Abs) against caspase-3 and their clinical relevance in systemic sclerosis (SSc). Anti-caspase-3 Ab was examined by enzyme-linked immunosorbent assay and immunoblotting. IgG anti-caspase-3 Ab levels in SSc patients were higher than in normal controls. SSc patients positive for IgG anti-caspase-3 Ab had significantly longer disease duration, more frequent presence of decreased %VC and %DLco, and elevated levels of serum immunoglobulin and erythrocyte sedimentation rates. IgG anti-caspase-3 Ab levels correlated positively with serum IgG levels, renal vascular resistance, and serum levels of 8-isoprostane. Immunoblotting analysis confirmed the presence of anti-caspase-3 Ab in sera from SSc patients. Caspase-3 enzymatic activity was inhibited by IgG isolated from SSc sera containing IgG anti-caspase-3 Ab. These results suggest that autoantibody against caspase-3 is generated in SSc and that this Ab is related to the severity of pulmonary fibrosis, vascular damage, and inflammation.

Topics: Adult; Apoptosis; Autoantibodies; Biomarkers; Caspase 3; Dinoprost; Female; Humans; Immunoglobulin G; Kidney Diseases; Male; Middle Aged; Predictive Value of Tests; Pulmonary Fibrosis; Renal Circulation; Scleroderma, Systemic; Vasculitis

Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis and vascular changes in the skin and internal organs with autoimmune background. It has been suggested that oxidative stress plays an important role in the development of SSc. To determine the prevalence and clinical correlation of autoantibody to methionine sulfoxide reductase A (MSRA), one of the antioxidant repair enzymes, in SSc, serum anti-MSRA autoantibody levels were examined in patients with SSc by enzyme-linked immunosorbent assay using recombinant MSRA. The presence of anti-MSRA antibody was evaluated by immunoblotting. To determine the functional relevance of anti-MSRA antibody in vivo, we assessed whether anti-MSRA antibody was able to inhibit MSRA enzymatic activity. Serum anti-MSRA antibody levels in SSc patients were significantly higher compared to controls and this autoantibody was detected in 33% of SSc patients. Serum anti-MSRA levels were significantly elevated in SSc patients with pulmonary fibrosis, cardiac involvement, or decreased total antioxidant power compared with those without them. Anti-MSRA antibodies also correlated positively with renal vascular damage determined as pulsatility index by color-flow Doppler ultrasonography of the renal interlobar arteries and negatively with pulmonary function tests. Furthermore, anti-MSRA antibody levels correlated positively with serum levels of 8-isoprostane and heat shock protein 70 that are markers of oxidative and cellular stresses. Remarkably, MSRA activity was inhibited by IgG isolated from SSc sera containing IgG anti-MSRA antibody. These results suggest that elevated anti-MSRA autoantibody is associated with the disease severity of SSc and may enhance the oxidative stress by inhibiting MSRA enzymatic activity.

Topics: Adult; Autoantibodies; Blood Vessels; Cytotoxicity, Immunologic; Dinoprost; Female; Hep G2 Cells; HSP70 Heat-Shock Proteins; Humans; Kidney; Male; Methionine Sulfoxide Reductases; Middle Aged; Pulmonary Fibrosis; Respiratory Function Tests; Scleroderma, Systemic; Ultrasonography, Doppler, Pulsed

Oxidative stress has been implicated in the pathogenesis of systemic sclerosis (SSc). Our objective was to determine whether SSc is associated with altered redox homeostasis in human saliva.. Study participants were 70 women with SSc and 120 female controls. 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-epi-prostaglandin F 2alpha (8-epi-PGF2alpha), and total protein carbonyls were assayed by ELISA to quantify oxidative damage to nucleic acids, lipids, and proteins, respectively, in whole nonstimulated saliva.. We observed a significantly positive association between salivary log protein carbonyls and SSc in a crude statistic (OR 9.06, p < 0.0001), and multivariable model adjusted for log 8-OHdG, log 8-epi-PGF2alpha, and antioxidant exposure (OR 9.26, p < 0.0001). No significant association was noted between SSc and salivary log 8-epi-PGF2alpha or log 8-OHdG.. Salivary redox homeostasis is perturbed in patients with SSc and may inform on the pathophysiology and presence of the disease (biomarkers) and efficacy of therapeutic interventions.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Biomarkers; Deoxyguanosine; Dinoprost; DNA Damage; Enzyme-Linked Immunosorbent Assay; Female; Homeostasis; Humans; Middle Aged; Oxidation-Reduction; Oxidative Stress; Protein Carbonylation; Saliva; Scleroderma, Systemic

Several lines of evidence suggest that the generation of reactive oxygen species (ROS) is of major importance in the pathogenesis of SSc. Protein and lipid damage have previously been demonstrated, but scarce data are available on oxidative damage to DNA. In patients with SSc, we evaluated levels of 8-hydroxy-2'-deoxyguanosine (8-oxodG), the main validated biomarker of endogenous oxidative damage to DNA, compared to levels of F2-isoprostane, a product of free radical-mediated peroxidation of arachidonic acid.. Urinary levels of 8-oxodG and 8-isoprostaglandin-F(2α) (8-iso-PGF(2α)) were determined by competitive ELISA method in consecutive SSc patients and controls matched for age and sex.. We included 80 unrelated SSc patients (72 women, mean age 56 ± 11 yrs) and 39 controls (33 women, mean age 64 ± 8 yrs). Urinary levels of 8-oxodG/creat and 8-iso-PGF(2α)/creat in SSc patients were found to be higher than in controls (6.5 ng/mg vs 3.7 ng/mg, p = 0.0001; and 11.4 ng/mg vs 4.2 ng/mg, p < 0.0001). In multivariate analysis, 8-oxodG levels were associated with the presence of pulmonary fibrosis on computerized tomography scan, decreased forced vital capacity, and decreased DLCO/alveolar volume. In patients with the diffuse cutaneous subset, a modified Rodnan skin score > 14 was independently associated with 8-oxodG levels. In SSc, 8-oxodG and 8-iso-PGF(2α) values were correlated (r = 0.32; p = 0.005).. Our study confirmed marked oxidative stress in SSc. We also found increased values of 8-oxodG in SSc patients and a relevant association with a fibrotic phenotype. The predictive value of this marker and its potential influence on fibrotic disturbances remain to be determined.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Deoxyguanosine; Dinoprost; DNA Damage; Female; Humans; Lipid Peroxidation; Middle Aged; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Scleroderma, Systemic

To determine the serum concentrations and clinical association of polymorphonuclear neutrophilic leukocyte (PMN) elastase in patients with systemic sclerosis (SSc).. Serum PMN elastase levels from 21 patients with limited cutaneous SSc (lSSc) and 32 with diffuse cutaneous SSc (dSSc) were examined by ELISA.. Serum PMN elastase levels were elevated in patients with SSc, especially dSSc, compared to healthy controls. SSc patients with elevated serum PMN elastase levels had more frequent presence of pulmonary fibrosis, arthritis, contracture of phalanges, and diffuse pigmentation. Anticentromere antibody was detected less frequently in SSc patients with elevated serum PMN elastase levels than in controls. Consistently, serum PMN elastase levels also correlated positively with serum levels of KL-6 and surfactant protein-D, serological markers for pulmonary fibrosis. Serum PMN elastase levels were also associated with levels of serum 8-isoprostane, an oxidative stress marker in SSc.. Serum PMN elastase levels were elevated in patients with SSc, and it was more prominent in patients with pulmonary fibrosis, suggesting that serum PMN elastase is a novel serological marker for SSc-related pulmonary fibrosis.

Topics: Adult; Aged; Biomarkers; Dinoprost; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leukocyte Elastase; Male; Middle Aged; Mucin-1; Oxidative Stress; Pulmonary Fibrosis; Pulmonary Surfactant-Associated Protein D; Scleroderma, Systemic

To determine the prevalence and clinical correlation of autoantibody to peroxiredoxin (Prx) I, an antioxidant enzyme, in patients with systemic sclerosis (SSc).. Serum samples from SSc patients (n = 70) and healthy controls (n = 23) were examined by ELISA using human recombinant Prx I. The presence of anti-Prx I antibody was further evaluated by immunoblotting analysis. To determine the functional relevance of anti-Prx I antibody in vivo, we assessed whether anti-Prx I antibody was able to inhibit Prx I enzymatic activity using yeast thioredoxin reductase system.. IgG anti-Prx I antibody levels in SSc patients were significantly higher than healthy controls and this autoantibody was detected in 33% of SSc patients. The presence of IgG anti-Prx I antibody was associated with longer disease duration, more frequent presence of pulmonary fibrosis, heart involvement, and anti-topoisomerase I antibody and increased levels of serum immunoglobulin and erythrocyte sedimentation rates. IgG anti-Prx I antibody levels also correlated positively with renal vascular damage and negatively with pulmonary function tests. Furthermore, anti-Prx I antibody levels correlated positively with serum levels of 8-isoprostane, a marker of oxidative stress. Immunoblotting analysis confirmed the presence of anti-Prx I antibody. Remarkably, Prx I enzymatic activity was inhibited by IgG isolated from SSc sera containing IgG anti-Prx I antibody.. These results suggest that elevated IgG anti-Prx I autoantibody is associated with the disease severity of SSc and that anti-PrxI antibody may enhance the oxidative stress by inhibiting Prx I enzymatic activity.

Topics: Adult; Aged; Antioxidants; Autoantibodies; Dinoprost; Enzyme Inhibitors; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoglobulin G; Male; Middle Aged; Oxidative Stress; Peroxidases; Peroxiredoxins; Pulsatile Flow; Scleroderma, Systemic; Severity of Illness Index; Vital Capacity

To determine serum levels and clinical correlation of 8-isoprostane, which is produced in vivo through free radical-catalysed peroxidation of arachidonic acid and reflects oxidative stress, in patients with systemic sclerosis (SSc).. Serum 8-isoprostane levels from 32 patients with diffuse cutaneous SSc (dSSc) and 25 patients with limited cutaneous SSc (lSSc) were examined by enzyme-linked immunosorbent assay.. Serum 8-isoprostane levels were elevated in dSSc and lSSc patients by 75-fold compared with normal controls (n=32). Serum 8-isoprostane levels correlated negatively with pulmonary function, such as percentage vital capacity and diffusion capacity for carbon monoxide, and correlated positively with renal vascular damage determined by colour flow Doppler ultrasonography. Serum 8-isoprostane levels also correlated positively with serum levels of IgG and anti-agalactosyl IgG autoantibody.. Increased 8-isoprostane levels correlated with the severity of pulmonary fibrosis, the extent of renal vascular damage and immunological abnormalities in SSc, suggesting that enhanced oxidative stress is related to the development of SSc.

Topics: Adult; Aged; Biomarkers; Carbon Monoxide; Dinoprost; Female; Humans; Male; Middle Aged; Oxidative Stress; Pulmonary Diffusing Capacity; Renal Circulation; Scleroderma, Diffuse; Scleroderma, Limited; Scleroderma, Systemic; Vascular Resistance; Vital Capacity

Microvascular dysfunction and increased oxidative stress are major hallmarks of the systemic sclerosis disease process. The primary objective of this study was to test whether there is a link between peak postocclusive hyperemia and urinary levels of the F2-isoprostane 15-F2t-IsoP (8-iso-PGF2alpha) in patients suffering from systemic sclerosis. We enrolled 43 patients suffering from systemic sclerosis, 33 patients with primary Raynaud's phenomenon (RP), and 25 healthy volunteers. Microvascular function was assessed using the postocclusive hyperemia monitored by laser Doppler flowmetry. Endothelium-independent response was monitored after 0.4 mg sublingual nitroglycerin. Oxidative stress status was assessed by urinary levels of the F2-isoprostane 15-F2t-IsoP using GC-MS. The peak postocclusive vascular conductance was altered in subjects with systemic sclerosis and primary RP compared to controls (respectively 28 (7-48), 30 (13-48), and 39.9 (13-63) mV/mm Hg, p = 0.01). F2-isoprostanes were increased in the systemic sclerosis group compared to primary Raynaud's phenomenon and healthy controls (respectively 230 (155-387), 182 (101-284), and 207 (109-291) pg/mg, p = 0.006). In patients suffering from systemic sclerosis, there was a significant inverse correlation between F2-isoprostanes and postocclusive hyperemia, expressed as raw data (R = -0.45, p = 0.007) or as an increase over baseline (R = -0.28, p = 0.04). Conversely, no correlation was found with the nitroglycerin response. In conclusion, we provide evidence that there is an inverse correlation between postocclusive hyperemia and urinary F2-isoprostane levels in patients suffering from systemic sclerosis. Whether oxygen free radicals initiate the vascular dysfunction or whether there is an initial trigger that initiates both processes will need to be further clarified in future studies.

Topics: Dinoprost; Humans; Hyperemia; Interleukin-1; Interleukin-6; Laser-Doppler Flowmetry; Lipid Peroxidation; Microcirculation; Oxidative Stress; Raynaud Disease; Scleroderma, Systemic; Skin

A new family of prostaglandin F2 isomers called F2-isoprostanes, produced by free radical peroxidation of arachidonic acid, has recently been described in vivo. Its quantification has been suggested to be a reliable measure of oxidant injury in vivo. The purpose of this study was to investigate urinary F2-isoprostane formation as an index of lipid peroxidation in scleroderma spectrum disorders.. Urine samples were obtained from 52 patients with systemic sclerosis (SSc; n = 37) or undifferentiated connective tissue diseases (UCTD; n = 15) and from 20 healthy volunteers. Urinary isoprostaglandin F2alpha type III (iPF2alpha-III) and 11-dehydro thromboxane B2 (11-dehydroTXB2) concentrations were determined using enzyme immunoassays.. The urinary concentration of iPF2alpha-III was approximately twice as high in patients (mean +/- SEM 229+/-16 pmoles/mmoles creatinine) as in controls (116+/-9 pmoles/mmoles creatinine) (P < 0.0001). However, the urinary concentration of iPF2alpha-III was not significantly different among patients with UCTD, limited SSc, and diffuse SSc (mean +/- SEM 221+/-27 versus 245+/-32 versus 220+/-25 pmoles/mmoles creatinine, respectively). No significant correlation was found between the urinary concentrations of iPF2alpha-III and 11-dehydroTXB2.. This study provides evidence of enhanced lipid peroxidation in both SSc and UCTD, and suggests a rationale for antioxidant treatment of SSc. Formation of F2-isoprostanes has to be investigated as a means for the evaluation of such therapy.

Topics: Adult; Aged; Dinoprost; F2-Isoprostanes; Female; Humans; Lipid Peroxidation; Male; Middle Aged; Scleroderma, Systemic; Thromboxane B2

Oxidative stress contributes to the pathophysiology of interstitial lung diseases, such as cryptogenic fibrosing alveolitis (CFA), fibrosing alveolitis associated with systemic sclerosis (FASSc) and sarcoidosis. F2-isoprostanes are a series of prostaglandin (PG) F2-like compounds produced in vivo independent of cyclooxygenase, as products of the radical-catalyzed lipid peroxidation. Measurement of the concentrations of F2-isoprostanes has proved to be valuable in assessing oxidative stress in vivo. The aim of this study was to measure 8-epi-PGF2alpha concentrations, one of the most abundant F2-isoprostane in humans, in bronchoalveolar lavage (BAL) in normal subjects and to compare them to those observed in patients with CFA (n = 9), FASSc (n = 8) and sarcoidosis (n = 10). 8-epi-PGF2alpha was detectable in BAL fluid in normal subjects (9.6 +/- 0.8 pg/ml) and its concentrations were increased approximately 5-fold in patients with CFA (47.4 +/- 7.0, p < 0.001) and FASSc (43.2 +/- 3.3, p < 0. 001). 8-epi-PGF2alpha was also increased in patients with sarcoidosis, although to a lesser extent (12.0 +/- 0.70 pg/ml, p < 0. 01). No correlation between 8-epi-PGF2alpha and either lung function tests or BAL cell types was observed in any group of patients. Our study shows that the level of oxidative stress is enhanced in patients with interstitial lung diseases as reflected by increased concentrations of 8-epi-PGF2alpha in BAL fluid.

Topics: Adult; Biomarkers; Bronchoalveolar Lavage Fluid; Bronchoscopy; Dinoprost; F2-Isoprostanes; Female; Free Radicals; Humans; Linear Models; Lipid Peroxidation; Lung Diseases, Interstitial; Male; Middle Aged; Nitric Oxide; Oxidative Stress; Pulmonary Fibrosis; Sarcoidosis; Scleroderma, Systemic; Tomography, X-Ray Computed

Intestinal pseudoobstruction and pneumatosis cystoides intestinalis are uncommon complications of progressive systemic sclerosis. We report a 26-year-old woman with this disorder who responded poorly to conventional treatment. Subcutaneous administration of octreotide, a long-acting somatostatin analogue, at a dose of 50 micrograms/day for 3 weeks, relieved symptoms such as nausea and bloating. There was also a marked decrease of intestinal gas accumulation, as documented on X-ray films.

Topics: Adult; Combined Modality Therapy; Dinoprost; Domperidone; Female; Gastrointestinal Motility; Humans; Intestinal Pseudo-Obstruction; Octreotide; Pneumatosis Cystoides Intestinalis; Scleroderma, Systemic

Topics: 6-Ketoprostaglandin F1 alpha; Dinoprost; Dinoprostone; Humans; Hypersensitivity, Delayed; Prostaglandin D2; Prostaglandins; Prostaglandins D; Prostaglandins E; Prostaglandins F; Psoriasis; Scleroderma, Systemic; Skin; Skin Diseases; Vitiligo