In law enforcement circles, the term pedophile is sometimes used informally to refer to any person who commits one or more sexually-based crimes that relate to legally underage victims. These crimes may include child sexual abuse, statutory rape, offenses involving child pornography, child grooming, stalking, and indecent exposure. One unit of the United Kingdoms Child Abuse Investigation Command is known as the "Paedophile Unit" and specializes in online investigations and enforcement work. Some forensic science texts, such as Holmes (2008), use the term to refer to offenders who target child victims, even when such children are not the primary sexual interest of the offender. FBI agent Kenneth Lanning, however, makes a point of distinguishing between pedophiles and child molesters. Civil and legal commitment
In the United States, following Kansas v. Hendricks, sex offenders who have certain mental disorders, including pedophilia, can be subject to indefinite civil commitment under various state laws (generically called SVP laws) and the federal Adam Walsh Child Protection and Safety Act of 2006.
Proton-pump inhibitors such as omeprazole and the anticonvulsant valproate have been found to increase the plasma concentrations of methotrexate, as have nephrotoxic agents such as cisplatin, the GI drug colestyramine, and dantrolene. Mechanism of action
Methotrexate is an antimetabolite of the antifolate type. It is thought to affect cancer and rheumatoid arthritis by two different pathways. For cancer, methotrexate competitively inhibits dihydrofolate reductase (DHFR), an enzyme that participates in the tetrahydrofolate synthesis. The affinity of methotrexate for DHFR is about 1000-fold that of folate. DHFR catalyses the conversion of dihydrofolate to the active tetrahydrofolate. Folic acid is needed for the de novo synthesis of the nucleoside thymidine, required for DNA synthesis. Also, folate is essential for purine and pyrimidine base biosynthesis, so synthesis will be inhibited. Methotrexate, therefore, inhibits the synthesis of DNA, RNA, thymidylates, and proteins.For the treatment of rheumatoid arthritis, inhibition of DHFR is not thought to be the main mechanism, but rather multiple mechanisms appear to be involved, including the inhibition of enzymes involved in purine metabolism, leading to accumulation of adenosine; inhibition of T cell activation and suppression of intercellular adhesion molecule expression by T cells; selective down-regulation of B cells; increasing CD95 sensitivity of activated T cells; and inhibition of methyltransferase activity, leading to deactivation of enzyme activity relevant to immune system function. Another mechanism of MTX is the inhibition of the binding of interleukin 1-beta to its cell surface receptor.