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playing a secondary role PTH secretion is controlled on a moment-to-moment basis by the calcium concentration of the ECF bathing the cells of the parathyroid glands Decreased plasma calcium concentration stimulates PTH secretion, and increased plasma concentration inhibits secretion Extracellular calcium concentration acts directly on the parathyroid glands by binding to a novel class of G protein linked receptors whose ligands are divalent cations The calcium receptor couples via an intracellular G protein to a signaling cascade that inhibits the secretion of PTH Thus, low extracellular calcium stimulates PTH secretion by removing a tonic inhibition This is a sensitive control system designed to keep free plasma calcium at about 5 mg/dL Phosphate also affects PTH secretion: Elevated phosphate stimulates PTH secretion by stimulating the capacity of the parathyroid gland to synthesize PTH, so that chronically high levels of phosphate lead to elevated PTH Vitamin D has slower inhibitory effects (discussed later), but calcium is the primary acute regulator PTH exerts at least 4 distinct effects on calcium homeostasis (summarized in Figure 10 3): 1 PTH actions on bone normally increase the movement of calcium from bone into the ECF They do this by stimulating the release of calcium across the bone membrane6 Without PTH, the equilibrium between hydroxyapatite and free calcium is shifted toward the formation of hydroxyapatite, causing the bone buffering system to take up calcium from the ECF and reduce plasma calcium concentration to a level incompatible with life On a slower basis, PTH also stimulates resorption carried out by osteoclasts It does this via a complex interaction between osteoblasts, which contain receptors for PTH, and osteoclasts In this manner, the immense store of calcium contained in bone is made available for the regulation of extracellular calcium concentration PTH stimulates the activation of vitamin D as described earlier (and this hormone then increases intestinal absorption of calcium) The blood concentration of vitamin D is subject to physiological control by PTH The major control point is the second hydroxylation step, the one that occurs in the kidneys This step is stimulated by PTH This action is highly adaptive If plasma calcium falls acutely, the subsequent increase in PTH immediately stimulates calcium transport from bone, thus restoring plasma calcium levels, and also stimulates calcium uptake (via vitamin D) from the GI tract This ensures that enough new calcium will enter the body to replace that borrowed from bone PTH increases renal-tubular calcium reabsorption, mainly by an action on the distal convoluted tubule and connecting tubule At these locations, it acts rapidly through activation of kinases that phosphorylate regulatory.

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Looking at your business, when are workers (or suppliers, or distributors, or customers) mobile and in need of time-sensitive data This is the question that will define the extent to which your business can possibly benefit from wireless data The nexus of these three factors defines the necessity for wireless data technology Interestingly, the factors are additive, meaning that more of one of them, such as more mobile workers, increases the potential of business value for wireless data Numerically, if you have 10 workers who are mobile out of 10,000 employees, you have less potential for improving your business than if 1,000 of your workers were mobile Likewise, if your mobile employees are mobile for all 8 hours of their work day, your potential for business advancements is greater than if your workers only spend one hour of their working day out of the office The other two factors have similar effects on the wireless data equation A higher need and greater time criticality of the data enhances the potential return of deploying the technology Repair teams that fix a broken industrial compressor system have a high degree of need for time sensitive data Every moment that they are delayed in placing it back on-line increases the cost of repair to their company and may also place in jeopardy their ability to meet their Service Level Agreement with their customer The breach of the service agreement may have penalties and other costs that add to the potential value of using wireless data to inform the repair team of how to do problem determination and take corrective action

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THE PARADOXES OF WINNING One last general thought on the subject of winning: Getting there may not be all you hoped for My father stated one of these paradoxes very succinctly:

As alluded to in Footnote 4, PTH either directly stimulates transport or causes release of calcium from hydroxyapatite by increasing its solubility Regardless of the mechanism, the result is an increased efflux of calcium from bone

We want to perfect ourselves so that we can win with less struggle and increasing ease, but the strange thing is that it s not the easy wins we ostensibly seek, but rather the difficult struggles to which we really look forward

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In the consumer space, geocentric wireless portals will drive consumption of mobile information, goods, and services Mobile handsets or terminals will be highly sensitive to geography as users travel to obtain goods or services instead of requiring delivery Therefore, mobile consumers are more likely to buy than to shop willy nilly The mobile user is likely to use a handset or dashboard wireless device to know what is physically available at nearby locations E-coupons, therefore, could be an important driver in the mobile marketplace, especially in North America, where over 90% of all consumer buying involves travel by car

regulation of CalCium and phosphate balanCe / 195

It s not much fun to play golf in a foursome in which the other three players are far worse than you are It s equally frustrating to be such a relatively lousy golfer that you slow down the other three members of your foursome We struggle to improve ourselves to be the best We want to win But winning isn t the only thing If we could take a pill to win every contest easily, most of us probably wouldn t take it As my father would say, the struggle s the thing

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