Growth control in colon epithelial cells: gadolinium enhances calcium-mediated growth regulation.

Gadolinium, a member of the lanthanoid family of transition metals, interacts with calcium-binding sites on proteins and other biological molecules. The overall goal of the present investigation was to determine if gadolinium could enhance calcium-induced epithelial cell growth inhibition in the colon. Gadolinium at concentrations as low as 1-5 µM combined with calcium inhibits proliferation of human colonic epithelial cells more effectively than calcium alone. Gadolinium had no detectable effect on calcium-induced differentiation in the same cells based on change in cell morphology, induction of E-cadherin synthesis, and translocation of E-cadherin from the cytosol to the cell surface. When the colon epithelial cells were treated with gadolinium and then exposed to increased calcium concentrations, movement of extracellular calcium into the cell was suppressed. In contrast, gadolinium treatment had no effect on ionomycin-induced release of stored intracellular calcium into the cytoplasm. Whether these in vitro observations can be translated into an approach for reducing abnormal proliferation in the colonic mucosa (including polyp formation) is not known. These results do, however, provide an explanation for our recent findings that a multi-mineral supplement containing all of the naturally occurring lanthanoid metals including gadolinium are more effective than calcium alone in preventing colon polyp formation in mice on a high-fat diet.

Neurostimulation for primary headache disorders, part 1: pathophysiology and anatomy, history of neuromodulation in headache treatment, and review of peripheral neuromodulation in primary headaches.

Neurostimulation for primary headaches is being increasingly utilized as a treatment modality. Use of neuromoduation has generated multiple case reports as well as some controlled studies. This article is the first of 2 systematic reviews of available data regarding neurostimulation for primary headache conditions. The pathophysiology, relative anatomy, theoretical mechanisms, and history of neurostimulation for primary headache are covered in this section, Part 1 of 2. The literature regarding peripheral neurostimulatory targets is also reviewed in Part 1. These peripheral targets include: percutaneous nerves, transcranial holocephalic, occipital nerves, auriculotemporal nerves, supraorbital nerves, cervical epidural, and sphenopalatine ganglia. Part 2 will focus on central stimulation, covering vagus nerve, and deep brain stimulation. Part 2 also contains an overall analysis of efficacy, safety, cost, patient selection, and suggestions for further study based on available evidence.