Amphotericin B molecules can form pores in the host membrane as well as the fungal membrane. This impairment in membrane barrier function can have lethal effects. Ergosterol, the fungal sterol, is more sensitive to amphotericin B than cholesterol, the common mammalian sterol. Reactivity with the membrane is also sterol concentration dependent. Bacteria are not affected as their cell membranes do not usually contain sterols. Amphotericin administration is limited by infusion-related toxicity. This is thought to result from innate immune production of proinflammatory cytokines. Biosynthesis
The natural route to synthesis includes polyketide synthase components. The carbon chains of Amphotericin B are assembled from sixteen C2 acetate and three C3propionate units by polyketide syntheses (PKSs). Polyketide biosynthesis begins with the decarboxylative condensation of a dicarboxylic acid extender unit with a starter acyl unit to form a β-ketoacyl intermediate. The growing chain is constructed by a series of Claisen reactions. Within each module, the extender units are loaded onto the current ACP domain by acetyl transferase (AT). The ACP-bound elongation group reacts in a Claisen condensation with the KS-bound polyketide chain. Ketoreductase (KR), dehydratase (DH) and enoyl reductase (ER) enzymes may also be present to form alcohol, double bonds or single bonds. After cyclisation, the macrolactone core undergoes further modification by hydroxylation, methylation and glycosylation. The order of these processes is unknown. History
It was originally extracted from Streptomyces nodosus, a filamentous bacterium, in 1955, at the Squibb Institute for Medical Research from cultures of an undescribed streptomycete isolated from the soil collected in the Orinoco River region of Venezuela.
It can affect men of any race and age. Psychosocial
Peyronies disease can also have psychological effects. While most men will continue to be able to have sexual relations, they are likely to experience some degree of erectile dysfunction. It is not uncommon to exhibit depression or withdrawal from their sexual partners. Causes
The underlying cause of Peyronies disease is unknown. Although, it is likely due to a buildup of plaque inside the penis due to repeated mild sexual trauma or injury during sexual intercourse or physical activity.Risk factors include diabetes mellitus, Dupuytrens contracture, plantar fibromatosis, penile trauma, smoking, excessive alcohol consumption, genetic predisposition, and European heritage. Diagnosis
A urologist may be able to diagnose the disease and suggest treatment. An ultrasound can provide conclusive evidence of Peyronies disease, ruling out congenital curvature or other disorders. Ultrasonography
On penile ultrasonography, the typical appearance is hyperechoic focal thickening of the tunica albuginea. Due to associated calcifications, the imaging of patients with Peyronies disease shows acoustic shadowing, as illustrated in figures below. Less common findings, attributed to earlier stages of the disease (still mild fibrosis), are hypoechoic lesions with focal thickening of the paracavernous tissues, echoic focal thickening of the tunica without posterior acoustic shadowing, retractile isoechoic lesions with posterior attenuation of the beam, and focal loss of the continuity of the tunica albuginea. In the Doppler study, increased flow around the plaques can suggest inflammatory activity and the absence of flow can suggest disease stability.