Thyrotoxic hypokalemic periodic paralysis: An overlooked pathology in western countries.

Thyrotoxic hypokalemic periodic paralysis (THPP) is a complication of hyperthyroidism that is mostly diagnosed in Asian populations; consequently, it can be difficult to recognize in western populations. THPP represents an endocrine emergency that can result in respiratory insufficiency, cardiac arrhythmias, and death. Its differential diagnosis from the other more common forms of hypokalemic paralysis is important to avoid inappropriate therapy. Here, we discuss the main pathogenetic hypotheses, clinical features, and therapies of this disease. We also report an example of THPP management in our primary care unit.

Glycerophosphoinositols inhibit the ability of tumour cells to invade the extracellular matrix.

The naturally occurring phosphoinositide metabolite, glycerophosphoinositol 4-phosphate, has recently been shown to induce rearrangements in the actin cytoskeleton through modulation of the small GTPases, Rac and Rho. Since this is directly linked to cell spreading and remodelling, we have evaluated the potential role of glycerophosphoinositol 4-phosphate and related metabolites in tumour cell invasion. The biological effects of these compounds were tested in a number of cellular activities related to cell spreading, including cell migration and cell invasion. We find that unlike other inositol-containing molecules, such as the inositol phosphates, glycerophosphoinositol and glycerophosphoinositol 4-phosphate prevent the invasion of epithelium-derived MDA-MB-231 breast carcinoma and A375MM melanoma cell lines through the extracellular matrix; this is due to a decreased ability to degrade matrix components. These data identify a specific activity of the glycerophosphoinositols that can be exploited for their development as novel anti-invasive drugs.

Dynamin participates in focal extracellular matrix degradation by invasive cells.

The degradation of extracellular matrix (ECM) by matrix metalloproteases is crucial in physiological and pathological cell invasion alike. Degradation occurs at specific sites where invasive cells make contact with the ECM via specialized plasma membrane protrusions termed invadopodia. Herein, we show that the dynamin 2 (Dyn2), a GTPase implicated in the control of actin-driven cytoskeletal remodeling events and membrane transport, is necessary for focalized matrix degradation at invadopodia. Dynamin was inhibited by using two approaches: 1) expression of dominant negative GTPase-impaired or proline-rich domain-deleted Dyn2 mutants; and 2) inhibition of the dynamin regulator calcineurin by cyclosporin A. In both cases, the number and extension of ECM degradation foci were drastically reduced. To understand the site and mechanism of dynamin action, the cellular structures devoted to ECM degradation were analyzed by correlative confocal light-electron microscopy. Invadopodia were found to be organized into a previously undescribed ECM-degradation structure consisting of a large invagination of the ventral plasma membrane surface in close spatial relationship with the Golgi complex. Dyn2 seemed to be concentrated at invadopodia.