Thiocyanate induces cell necrosis and fibrosis in selenium- and iodine-deficient rat thyroids: a potential experimental model for myxedematous endemic cretinism in central Africa

Thyroid destruction leading to endemic myxoedematous cretinism is highly prevalent in central Africa, where iodine (I) and selenium (SE) deficiencies as well as thiocyanate (SCN) overload are combined. All three factors have been studied experimentally in the etiology of the disease, but they have never been studied in combination. In a model using rats, we have previously shown that combining I and SE deficiencies increases the sensitivity of the thyroid to necrosis after iodide overload, an event unlikely to occur in the African situation. To develop a model that would more closely fit with the epidemiological findings, we have determined whether an SCN overload would also result in thyroid necrosis as does the I overload. The combination of the three factors increased by 3.5 times the amount of necrotic cells, from 5.5 +/- 0.3% in the I-SE+ thyroids to 18.9 +/- 1.6% in the I-SE-SCN-overloaded ones. Methimazole administration prevented the SCN-induced necrosis. SE- thyroids evolved to fibrosis, whereas SE+ thyroids did not. TGFbeta was prominent in macrophages present in SE- glands. Thyroid destruction in central Africa might therefore originate from the interaction of three factors: I and SE deficiencies by increasing H(2)O(2) accumulation, SE deficiency by decreasing cell defense and promoting fibrosis, and SCN overload by triggering follicular cell necrosis.     

Late left ventricular pseudoaneurysm formation following subacute myocardial infarction

We describe a patient with a subacute inferior myocardial infarction who developed a pseudo-aneurysm more than 18 days after the acute event. This is an unusual case with three different complications of a myocardial infarction: Firstly, ventricular rupture is usually the result following transmural myocardial infarction without reperfusion. However, coronary angiography confirmed reperfusion after late thrombolysis in this patient. The subacute rupture could potentially be caused or aggravated by the late thrombolysis. Secondly, this patient developed a mural apical thrombus in a non-infarcted region. It seems most likely that the new infarct caused a low flow state which enhanced thrombus formation. Against expectations, this developed at the apex rather than the site of the recent inferior wall myocardial infarction. Thirdly, we documented the development of a pseudo-aneurysm more than 18 days after the myocardial infarction. This complication is rarely seen at this stage after a myocardial infarction, as most pseudo-aneurysms are formed within 7 days after a myocardial infarction. We have beautifully visualised the apical thrombus and pseudo-aneurysm with echocardiography. This report shows that serial echocardiography is a very useful tool in evaluating the patient's clinical and cardiac status in the period after a myocardial infarction.     

Age at menarche in rural France

Data upon age at menarche have been collected among 254 schoolgirls of a relatively endogamous rural population in central France. The median age at menarche estimated by probits was 13·05±0·18, SD1·42. This accords well with results obtained from urban samples in the years 1965–68. Both rural and urban samples give a median age 0·5 year earlier than data from a national survey performed in 1950.     

Morphometry and localization of the temporal transverse Heschl’s gyrus in magnetic resonance imaging: a guide for cortical stimulation of chronic tinnitus

Purpose

Subjective tinnitus is considered a phantom auditory phenomenon. Recent studies show that electrical or magnetic stimulation of the cortex can alleviate some tinnitus. The usual target of the stimulation is the primary auditory cortex (PAC) on Heschl’s gyrus (HG). The objective of this study was to specify the anatomy of HG by magnetic resonance imaging (MRI).

Methods

Cerebral MRI of 60 patients with chronic tinnitus, carried out before neuronavigated repetitive transcranial magnetic stimulation targeting the auditory cortex, were included. 3D-T1 MRI was reformatted in Talairach–Tournoux’s stereotactic space, then the following steps were performed: morphometry of HG, localization of the probabilistic center of the PAC (pcPAC) chosen at the junction between the medial third and the lateral two-thirds of HG, relative to external and cortical landmarks, and identification of its coordinates relative to the bicommissural line (AC-PC).

Results

In relation to external landmarks, the pcPAC was identified around 5 cm above the root of the helix of the ear in the direction of a point on the vertex located 4 cm behind the coronal suture, for both sides. In Talairach–Tournoux’s stereotactic space with the anterior commissure as the origin, the pcPAC coordinates were x = 43, y = ?20, z = 6.8 on the right side, and x = ?42.5, y = ?21.5, and z = 6.5 on the left. Probabilistic maps of the presence of HG pointed to a relative contraction of data in space, despite inter- and intraindividual differences.

Conclusion

The choice of our stimulation target was established in the middle of the theoretical position of the PAC. MRI allows a reliable identification of the target structure.     

Annexin A1–containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair

Epithelial restitution is an essential process that is required to repair barrier function at mucosal surfaces following injury. Prolonged breaches in epithelial barrier function result in inflammation and further damage; therefore, a better understanding of the epithelial restitution process has potential for improving the development of therapeutics. In this work, we demonstrate that endogenous annexin A1 (ANXA1) is released as a component of extracellular vesicles (EVs) derived from intestinal epithelial cells, and these ANXA1-containing EVs activate wound repair circuits. Compared with healthy controls, patients with active inflammatory bowel disease had elevated levels of secreted ANXA1-containing EVs in sera, indicating that ANXA1-containing EVs are systemically distributed in response to the inflammatory process and could potentially serve as a biomarker of intestinal mucosal inflammation. Local intestinal delivery of an exogenous ANXA1 mimetic peptide (Ac2-26) encapsulated within targeted polymeric nanoparticles (Ac2-26 Col IV NPs) accelerated healing of murine colonic wounds after biopsy-induced injury. Moreover, one-time systemic administration of Ac2-26 Col IV NPs accelerated recovery following experimentally induced colitis. Together, our results suggest that local delivery of proresolving peptides encapsulated within nanoparticles may represent a potential therapeutic strategy for clinical situations characterized by chronic mucosal injury, such as is seen in patients with IBD.