Human cartilaginous endplate degeneration is induced by calcium and the extracellular calcium-sensing receptor in the intervertebral disc.

The cartilaginous endplates (CEPs) are thin layers of hyaline cartilage found adjacent to intervertebral discs (IVDs). In addition to providing structural support, CEPs regulate nutrient and metabolic exchange in the disc. In IVD pathogenesis, CEP undergoes degeneration and calcification, compromising nutrient availability and disc cell metabolism. The mechanism(s) underlying the biochemical changes of CEP in disc degeneration are currently unknown. Since calcification is often observed in later stages of IVD degeneration, we hypothesised that elevations in free calcium (Ca2+) impair CEP homeostasis. Indeed, our results demonstrated that the Ca2+ content was consistently higher in human CEP tissue with grade of disc degeneration. Increasing the levels of Ca2+ resulted in decreases in the secretion and accumulation of collagens type I, II and proteoglycan in cultured human CEP cells. Ca2+ exerted its effects on CEP matrix protein synthesis through activation of the extracellular calcium-sensing receptor (CaSR); however, aggrecan content was also affected independent of CaSR activation as increases in Ca2+ directly enhanced the activity of aggrecanases. Finally, supplementing Ca2+ in our IVD organ cultures was sufficient to induce degeneration and increase the mineralisation of CEP, and decrease the diffusion of glucose into the disc. Thus, any attempt to induce anabolic repair of the disc without addressing Ca2+ may be impaired, as the increased metabolic demand of IVD cells would be compromised by decreases in the permeability of the CEP.

Postpartum psychosis and postpartum thyroiditis.

The term postpartum psychosis refers to a group of severe and heterogeneous disorders with psychotic symptoms that occur most frequently in the context of a mood disorder during the postpartum period. We report a case of 'postpartum psychosis' possibly associated with postpartum thyroiditis in a 29 year-old woman. The appearance of psychotic symptoms was chronologically related to the onset of postpartum thyroiditis and resolution of psychosis synchronized with the achievement of biochemical euthyroidism. The patient had typical symptoms of 'classic postpartum psychosis' (a historical term not included in DSM-IV, but used frequently by many physicians to describe diagnostic and therapeutic challenges posed by puerperal psychoses). Three months postpartum, the patient began to believe that she was pregnant with the Christ child, although she was not pregnant. Her delusions resolved around the 'pregnancy' and harm to her 'unborn' child. She also believed that her child (Jesus) was going to be killed. Other key symptoms included hallucinations, mixed mood symptoms, agitation and transient disorientation. Her DSM-IV diagnosis on admission was major depression with psychotic features and her discharge diagnosis (most likely diagnosis) was psychotic disorder due to thyrotoxicosis caused by postpartum thyroiditis. The differential diagnosis of co-occurring psychosis and postpartum thyroiditis can be examined relative to four possibilities: (1) psychosis due to thyrotoxicosis caused by postpartum thyroiditis; (2) a coincidence (no association between psychosis and postpartum thyroiditis); (3) precipitation of psychotic symptoms and disorientation related to a postpartum thyroiditis in a woman with a pre-existing mood disorder; or (4) both psychosis and thyroiditis caused by a pre-existing defect in autoimmunity. The authors stress the importance of early diagnosis and prompt treatment of postpartum psychosis. They discuss the indications for thyroid screening in postpartum psychoses. Further research is needed to clarify the nosology and mechanisms of severe postpartum disorders and to elucidate treatment-relevant and etiologically-distinct subsets of postpartum psychosis.

Time course of appearance and disappearance of human mast cell tryptase in the circulation after anaphylaxis.

Tryptase, a neutral protease of human mast cells, is a potentially important indicator of mast cell involvement in various clinical conditions. The current study examined the time course of appearance and disappearance of tryptase in the circulation after an anaphylactic event and the stability of both endogenous and exogenous tryptase in terms of freeze-thawing and temperature. The peak level of tryptase after an experimentally induced systemic anaphylactic reaction occurred 1-2 h after the initiating bee sting in each of three subjects, in contrast to histamine levels which peaked at 5-10 min. In some cases elevated levels of tryptase may not be detected during the initial 15-30 min. Tryptase levels then declined under apparent first order kinetics with a t1/2 of approximately 2h. Similar disappearance kinetics were observed for two subjects presenting in the emergency room with immediate type reactions, one with severe asthma after indomethacin ingestion, the other with systemic anaphylaxis after a bee sting. Histamine levels declined rapidly and were back to baseline by 15-60 min. Measured levels of tryptase in serum or plasma were not diminished by up to four freeze-thaw cycles. Incubation of serum samples taken from subjects with elevated levels of tryptase at 22 and 37 degrees C indicated that greater than 50% of endogenous tryptase was still detected after 4 d. Purified tryptase added to serum or plasma and incubated as above was less stable: approximately 50% of exogenous tryptase in serum and approximately 15% in plasma was detected after 2d of incubation. Therefore, optimally samples should be stored frozen, but even those stored at room temperature for up to 4 d should be satisfactory. The best time to obtain samples for tryptase determinations is 1-2 h after the precipitating event, but depending on the magnitude of the initial response elevated levels of tryptase may be present in the circulation for several hours.