Crush syndrome (also traumatic rhabdomyolysis or Bywaters syndrome) is a medical condition characterized by major shock and kidney failure after a crushing injury to skeletal muscle. Crush injury is compression of the arms, legs, or other parts of the body that causes muscle swelling and/or neurological disturbances in the affected areas of the body, while crush syndrome is localized crush injury with systemic manifestations. Cases occur commonly in catastrophes such as earthquakes, to individuals that have been trapped under fallen or moving masonry. People with crushing damage present some of the greatest challenges in field medicine, and may need a physicians attention on the site of their injury. Appropriate physiological preparation of the injured is mandatory. It may be possible to free the patient without amputation; however, field amputations may be necessary in drastic situations. Pathophysiology
Seigo Minami, a Japanese physician, first reported the crush syndrome in 1923. He studied the pathology of three soldiers who died in World War I due to kidney failure. The renal changes were due to the buildup of excess myoglobin, resulting from the destruction of muscles from lack of oxygen. These changes can also be seen in persons who are buried alive. The progressive acute kidney failure is because of acute tubular necrosis. The syndrome was later described by British physician Eric Bywaters in patients during the 1941 wartime bombing of London (the Blitz). It is a reperfusion injury that appears after the release of the crushing pressure.
More recently, a growing body of studies has provided evidence that derangement of insulin signaling underlying type-2 diabetes significantly increase the risk of cognitive impairment and Alzheimers disease (AD) progression (12). On this ground, the direct administration of STZ in the brain (i.e., by intracerebroventricular (ICV) infusion) has been used to develop an animal model of brain insulin resistance to mimic in rodents the pathophysiology of sporadic AD, which represents the most common form of AD in humans. STZ infusion in the brain induced accumulation of Amyloid beta (Aβ) protein (13), oxidative stress and cognitive impairment (14). Notably, there is now evidence that STZ infusion within the brain produced up-regulation of amyloid precursor protein (APP), tau hyperphosphorylation and neuroinflammation (15). This study (15), also shows that treatment with the cleavage-specific anti-tau 12A12 monoclonal antibody (mAb) can relieve APP upregulation, neuroinflammation and reduce cerebral oxidative stress, mitochondrial impairment, synaptic and histological alterations, as well as induce a nearly complete recovery of cognitive impairment in the STZ-induced SAD mouse model. Streptozotocin is now long off patent and many generic formulations are available. Biosynthesis
Recent advancements in understanding the biosynthesis of this natural product have been made by Balskus et al. In short, the authors found the gene cluster responsible for production of Streptozotocin in Streptomyces achromogenes and identified novel function of a non-heme iron enzyme, SznF, which forms the N-N bond in the N-nitrosourea pharmacophore by oxidative rearrangement. See also
Alloxan

References
12. Velayudhan, L. et al. Risk of developing dementia in people with diabetes and mild cognitive impairment. Br.