Development
In the newborn, the symphysis pubis is 9–10 mm in width, with thick cartilaginous end-plates. By mid-adolescence the adult size is achieved. During adulthood the end-plates decrease in width to a thinner layer. Degeneration of the symphysis pubis accompanies aging and postpartum. Women have a greater thickness of this pubic disc which allows more mobility of the pelvic bones, hence providing a greater diameter of pelvic cavity during childbirth. Function
Analysis of the pelvis shows the skinny regions function as arches, transferring the weight of the upright trunk from the sacrum to the hips. The symphysis pubis connects these two weight-bearing arches, and the ligaments that surround this pelvic region maintain the mechanical integrity. The main motions of the symphysis pubis are superior/inferior glide and separation/compression. The functions of the joint are to absorb shock during walking and allow delivery of a baby. Clinical significance
Injury
The pubic symphysis widens slightly when the legs are stretched far apart. In sports where these movements are often performed, the risk of a pubic symphysis blockage is high, in which case, after completion of the movement, the bones at the symphysis do not realign correctly and can get jammed in a dislocated position. The resulting pain can be severe, especially when further strain is put upon the affected joint. In most cases, the joint can only be successfully reduced into its normal position by a trained medical professional. Disease
Metabolic diseases, such as renal osteodystrophy, produce widening, while ochronosis results in calcific deposits in the symphysis.
However, the intra-cellular thio-nucleotide metabolites of thioguanine (6-TGN) have longer half-lives and can therefore be measured after thioguanine is eliminated from the plasma. Thioguanine is catabolized (broken down) via two pathways. One route is through the deamination by the enzyme guanine deaminase to 6-thioxanthine, which has minimal anti-neoplastic activity, then by oxidation by xanthine oxidase of the thioxanthine to thiouric acid. This metabolic pathway is not dependent on the efficacy of xanthine oxidase, so that the inhibitor of xanthine oxidase, the drug allopurinol, does not block the breakdown of thioguanine, in contrast to its inhibition of the breakdown of the related thiopurine 6-mercaptopurine. The second pathway is the methylation of thioguanine to 2-amino-6-methylthiopurine, which is minimally effective as an anti-neoplastic and significantly less toxic than thioguanine. This pathway also is independent of the enzyme activity of xanthine oxidase. Mechanism of action
6-Thioguanine is a thio analogue of the naturally occurring purine base guanine. 6-thioguanine utilises the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) to be converted to 6-thioguanosine monophosphate (TGMP). High concentrations of TGMP may accumulate intracellularly and hamper the synthesis of guanine nucleotides via the enzyme Inosine monophosphate dehydrogenase (IMP dehydrogenase), leading to DNA mutations.TGMP is converted by phosphorylation to thioguanosine diphosphate (TGDP) and thioguanosine triphosphate (TGTP). Simultaneously deoxyribosyl analogs are formed, via the enzyme ribonucleotide reductase. The TGMP, TGDP and TGTP are collectively named 6-thioguanine nucleotides (6-TGN).