In bacterial meningitis, bacteria reach the meninges by one of two main routes: through the bloodstream (hematogenous spread) or through direct contact between the meninges and either the nasal cavity or the skin. In most cases, meningitis follows invasion of the bloodstream by organisms that live on mucosal surfaces such as the nasal cavity. This is often in turn preceded by viral infections, which break down the normal barrier provided by the mucosal surfaces. Once bacteria have entered the bloodstream, they enter the subarachnoid space in places where the blood–brain barrier is vulnerable – such as the choroid plexus. Meningitis occurs in 25% of newborns with bloodstream infections due to group B streptococci; this phenomenon is much less common in adults. Direct contamination of the cerebrospinal fluid may arise from indwelling devices, skull fractures, or infections of the nasopharynx or the nasal sinuses that have formed a tract with the subarachnoid space (see above); occasionally, congenital defects of the dura mater can be identified.The large-scale inflammation that occurs in the subarachnoid space during meningitis is not a direct result of bacterial infection but can rather largely be attributed to the response of the immune system to the entry of bacteria into the central nervous system. When components of the bacterial cell membrane are identified by the immune cells of the brain (astrocytes and microglia), they respond by releasing large amounts of cytokines, hormone-like mediators that recruit other immune cells and stimulate other tissues to participate in an immune response.
Tiopronin, sold under the brand name Thiola, is a medication used to control the rate of cystine precipitation and excretion in the disease cystinuria. Due to the rarity of the disorder, tiopronin falls under the classification of an orphan drug. It is somewhat similar to penicillamine in both chemistry and pharmacology.A generic version of tiopronin is available in the United States as of April 2021. Uses
Tiopronin is used primarily for cystinuria and is well known in the cystinuric community. Depending on the severity of a persons cystinuria, tiopronin may be taken for life, possibly starting in early childhood. The drug works by reacting with urinary cysteine to form a more soluble, disulfide linked, tiopronin-cysteine complex. Side effects
Tiopronin may present a variety of side effects, which are broadly similar to those of D-penicillamine and other compounds containing active sulfhydryl groups. Its pharmacokinetics have been studied. Society and culture
In the U.S., the drug was marketed by Mission Pharmacal at $1.50 per pill, but in 2014 the rights were bought by Retrophin, owned by Martin Shkreli, and the price increased to $30 per pill for a 100 mg capsule.In 2016 Imprimis Pharmaceuticals introduced a lower cost version marketed as a compounded drug. Research
It may also be used for Wilsons disease (an overload of copper in the body), and has also been investigated for the treatment of arthritis, though tiopronin is not an anti-inflammatory.Tiopronin is also sometimes used as a stabilizing agent for metal nanoparticles. The thiol group binds to the nanoparticles, preventing coagulation. References
External links
"Tiopronin". Drug Information Portal.