User:KBlott/SK

=Peyronie’s Disease= Peyronie’s Disease is an inflammation and fibrosis of the tunica albuginea. The initial acute phase is characterized by the presence of a tender palpable nodule, pain on erection, and the growth of fibrous plaques. Acute Peyronie’s disease is progressive in 30% of individuals without treatment and spontaneous resolution is rare. The chronic phase is characters by penile narrowing or dorsal (45%) or lateral (29%) curvature.

Pentoxifylline
Transforming growth factor-beta1 (TGF-beta1) contributes to the pathogenesis of Peyronie's disease. Pentoxifylline (PTX) antagonizes this affect and is used to treat Peyronie's disease.

Type 1 interferon
Peyronie's disease responds to treatment with exogenous alpha interferon.

Calcium channel blockers
Calcium channel blockers modulate metabolism of collagens within the extracellular matrix and soften Peyronie’s disease associated plaque.

Association with metabolic syndrome
Peyronie’s Disease is associated with hypercholesterolemia, diabetes, and hypertension. This suggests that metabolic syndrome and Peyronie’s Disease are likely to share a common risk factor. Metabolic syndrome in chickens has been linked to alpha herpes virus infection. Metabolic syndrome in humans has been associated with alpha herpes virus infection, beta herpes virus infection, and Helicobacter pylori infection.

Type 1 interferon
Type 1 interferon directly inhibits maturation of a broad spectrum of viral infections.

Peyronie’s disease and idiopathic pulmonary fibrosis
Elastic fibers in the tunica albuginea are disordered in Peyronie's disease associated plaque. Elastin is also expressed in the lungs. Idiopathic pulmonary fibrosis is associated with beta herpes virus infection.

Evidence of an autoimmune response in Peyronie’s Disease
Peyronie's disease is associated with increased serum levels of anti-elastin antibodies.

Indirect evidence of association with beta herpes virus infection
Over-expression of p53 has been reported in cell lines derived from individuals with Peyronie's disease. Human cytomegalovirus elevates levels of the cellular protein p53 in infected fibroblasts.

Indirect evidence of association with gamma herpes virus infection
Basic fibroblast growth factor is over expressed in cell lines derived from individuals with Peyronie's disease. The human herpes virus-8 (HHV-8) is a recently described virus which induces over-expression of basic fibroblast growth factor. Alpha interferon inhibits the replication of this virus.

HLA-DQ5
Individuals with an HLA-DQ5 genotype are at an increased risk for Peyronie's disease. One small study has linked the HLA-DQ5 genotype with an increased susceptibility Helicobacter pylori infection.

Type 2 interferon
Nitric oxide inhibits plaque formation. Mitochondrial nitric oxide biosynthesis can be stimulated with exogenous gamma interferon. The inhibitory effects of IFN-gamma on the TGF-beta pathway does not appear in Peyronie's disease. Helicobacter pylori disrupts STAT1-mediated Gamma Interferon-Induced signal transduction in epithelial Cells.

=Iatrogenic Fanconi syndrome=

Iatrogenic Fanconi syndrome appears to occur in AIDS carriers who combine older antiretrovirals (such as d4t) which inhibit mitochondrial DNA synthesis with newer antiretrovirals (such as tenofovir) that inhibit the organic anion transporter Multidrug resistance-associated protein 2 (MRP2). MRP2 is expressed in on the apical membrane of proximal renal tubule endothelial cells where it transports organic anions from the cytoplasm of the endothelial cells into the lumen of the nephron. Inhibition of these transporters causes the build up of organic anions in the cytoplasm. If those organic anions happen to include mitochondrial DNA polymerase inhibitors, such as d4T, this can impair mitochondrial replication. This in turn impairs the endothelial cell functions which includes reuptake of glucose causing glucosuria. The current treatment for this condition is to drop the medications that inhibit mitochondrial DNA synthesis.