The primary function of thyroid gland is to metabolize iodide by synthesizing thyroid hormones that are critical regulators of growth, development and metabolism in virtually all tissues. To date, research on thyroid morphogenesis was missing an efficient stem-cell model system which allows to recapitulate in vitro the molecular and morphogenic events regulating thyroid follicular cells differentiation and subsequent assembly into functional thyroid follicles. Here we report that a transient overexpression of the transcription factors NKX2.1 and PAX8 is sufficient to direct mouse embryonic stem-cells (mESC) differentiation into thyroid follicular cells which organized into three-dimensional follicular structures when treated with thyrotropin. Those in vitro derived follicles showed significant iodide organification activity. Importantly, when grafted in vivo into athyreoid mice, these follicles rescued thyroid hormone plasma levels and promoted subsequent symptomatic recovery. Thus, mESC can be induced to differentiate into thyroid follicular cells in vitro and generate functional thyroid tissue.

European Society of Anaesthesiology.

No abstract

Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine.

LDL particles must be modified in the arterial wall to be taken up by macrophages at an excessive rate, leading to foam cell formation. Phospholipase A2 (PLA2) has been shown to modify LDL particles in vitro by degrading its phospholipids, resulting in enhanced uptake by macrophages. Reaction products of PLA2 are lysophospholipids and nonesterified fatty acids (mainly arachidonic acid), which are precursors of potent inflammatory mediators and which have been found in atherosclerotic regions of the arterial wall. To elucidate the expression of PLA2 in normal and diseased arteries, frozen tissue sections of human nonatherosclerotic mesenteric artery and carotid plaques were examined by immunohistochemistry using specific antibodies against secretory PLA2 types I and II and cytosolic PLA2 (85 kd). Secretory PLA2 type I was not detected. High expression of secretory PLA2 type II was found throughout the media in both normal and atherosclerotic artery specimens, in which smooth muscle cells dominated. Cytosolic PLA2 was found exclusively in diseased artery, mainly in the intima in regions with an inflammatory infiltrate consisting of macrophages and smooth muscle cells. Furthermore, both normal and atherosclerotic artery possessed substantial PLA2 activity. It is suggested that secretory PLA2 type II could play an important role in early atherogenesis because it is present in the preatherosclerotic arterial wall, where it may lead to LDL modification, foam cell formation, and activation of immune mechanisms.

Monocarboxylate transporter 8 acts as a specific cell membrane transporter for thyroxine and especially triiodothyronine into target cells. It is expressed in brain neurons and in many other tissues. The monocarboxylate transporter 8 gene resides on chromosome Xq13.2. An 11-month-old male infant was referred because of severe hypotonia from early life and global developmental delay. Thyroid-function tests showed normal thyrotropin levels and the characteristic for the disorder, including high serum triiodothyronine and low thyroxine concentrations. Molecular analysis of the monocarboxylate transporter 8 gene showed that the patient was hemizygous for a novel missense mutation P537L. This case highlights the importance of determining thyroid hormone levels, especially triiodothyronine, in infants with severe neonatal hypotonia.

HSP72 and eNOS, which may be associated with cardioprotection in ischemic preconditioning, are increased in atrial tissue of patients with unstable angina. Activation of NFkappaB and AP-1, which regulate a battery of inflammatory genes, was found in hearts of unstable patients. NFkappaB activation may induce a myocardial proinflammatory state, possibly making the unstable myocardium more susceptible to the inflammation induced by open heart surgery.

Acute administration of glucocortiocoids reduces inflammation. Increasing knowledge of the mechanisms of action indicate that pretreatment with glucocorticoids could have organ-protective effects. We investigated whether pretreatment with methylprednisolone (MP) protected the heart against ischemia-reperfusion dysfunction, and we hypothetized that this protection might be due to induction of the cardioprotective heat shock protein 72 (HSP72). Rats were given vehicle or MP-40 mg/kg im as a double injection starting either 24 or 120 h (5 days) before their hearts were excised for Langendorff perfusion (n = 6-11 hearts in each group). MP improved left ventricular function and coronary flow during reperfusion after 30 min of global ischemia and reduced infarct size. Cardiac HSP72 gradually increased in a 24-h time course after MP treatment, and the increase was sustained 5 days afterward (immunoblotting). HSP72 mRNA was either reduced or unchanged, indicating a posttranscriptional regulation. Pretreatment with hydrocortisone or dexamethasone (n = 7-8 hearts of each) similarily increased cardiac HSP72 24 h afterward. This paper demonstrates that glucocorticoids increase cardiac HSP72 and protect organ function against ischemia-reperfusion injury.