Withdrawal of methamphetamine in dependent persons may lead to post-acute withdrawal which persists months beyond the typical withdrawal period.Magnetic resonance imaging studies on human methamphetamine users have also found evidence of neurodegeneration, or adverse neuroplastic changes in brain structure and function. In particular, methamphetamine appears to cause hyperintensity and hypertrophy of white matter, marked shrinkage of hippocampi, and reduced gray matter in the cingulate cortex, limbic cortex, and paralimbic cortex in recreational methamphetamine users. Moreover, evidence suggests that adverse changes in the level of biomarkers of metabolic integrity and synthesis occur in recreational users, such as a reduction in N-acetylaspartate and creatine levels and elevated levels of choline and myoinositol.Methamphetamine has been shown to activate TAAR1 in human astrocytes and generate cAMP as a result. Activation of astrocyte-localized TAAR1 appears to function as a mechanism by which methamphetamine attenuates membrane-bound EAAT2 (SLC1A2) levels and function in these cells.Methamphetamine binds to and activates both sigma receptor subtypes, σ1 and σ2, with micromolar affinity. Sigma receptor activation may promote methamphetamine-induced neurotoxicity by facilitating hyperthermia, increasing dopamine synthesis and release, influencing microglial activation, and modulating apoptotic signaling cascades and the formation of reactive oxygen species. Addictive
Current models of addiction from chronic drug use involve alterations in gene expression in certain parts of the brain, particularly the nucleus accumbens. The most important transcription factors that produce these alterations are ΔFosB, cAMP response element binding protein (CREB), and nuclear factor kappa B (NFκB).
Pessaries require a provider to fit the device, but most can be removed, cleaned, and replaced by the woman herself. Pessaries should be offered to women considering surgery as a non-surgical alternative. Surgery
With surgery (for example native tissue repair, biological graft repair, absorbable and non-absorbable mesh repair, colpopexy, colpocleisis). Surgery is used to treat symptoms such as bowel or urinary problems, pain, or a prolapse sensation. Evidence does not support the use of transvaginal surgical mesh compared with native tissue repair for anterior compartment prolapse owing to increased morbidity. For posterior vaginal repair, the use of mesh or graft material does not seem to provide any benefits. Safety and efficacy of many newer meshes is unknown. The use of a transvaginal mesh in treating vaginal prolapses is associated with side effects including pain, infection, and organ perforation. Transvaginal repair seems to be more effective than transanal repair in posterior wall prolapse, but adverse effects cannot be excluded. According to the FDA, serious complications are "not rare." A number of class action lawsuits have been filed and settled against several manufacturers of TVM devices.Compared to native tissue repair, transvaginal permanent mesh probably reduces womens perception of vaginal prolapse sensation and probably reduces the risk of recurrent prolapse and of having repeat surgery for prolapse. On the other hand, transvaginal mesh probably has a greater risk of bladder injury and of needing repeat surgery for stress urinary incontinence or mesh exposure.