Bone digester

Ninety percent of cancer deaths are caused by metastatic rather than primary tumors. Define metastasis. Explain the rationale for the following new cancer treatments (a) batima-stat, an inhibitor of matrix metalloproteinases and of the plasminogen activator receptor, (b) antibodies that block the function of integrins, integral membrane proteins that mediate attachment of cells to the basal laminae and extracellular matrices of various tissues, and (c) bisphosphonate, which inhibits the function of bone-digesting osteoclasts. 

Otto von Guericke designed the world s first vacuum pump in 1650. Robert Boyle and Robert Hooke built an air pump in 1656. Pressure exerted by a fluid was found to be inversely proportional to volume, according to the Boyle s law. Denis Pipin, an associate of Boyle, built a bone digester that was used to raise high pressure steam. The idea of a piston and cylinder emanated from Pipin, although Tom Savery built the first engine in 1697. 

Samples of animal bones weighing approximately 3 g are ashed at 600 °C until the entire bone is ash-white. Samples are then crushed in a mortar and pestle. A portion of the sample is digested in HCl and diluted to a known volume. The concentrations of zinc and strontium are determined by atomic absorption. The analysis for strontium illustrates the use of a protecting agent as La(N03)3 is added to prevent an interference due to the formation of refractory strontium phosphate. 

In frames of the present work the problems of elemental analysis of human bio-substrates (blood semm, hair and bones) are diseussed. Sample pretreatment proeedures using ash and mineral aeids digestion were developed. The main sourees of systematie errors were studied and their elimination ways were suggested. 

What determines the differenee in 5 C between eollagen and bone carbonate apatite (bioapatite) for animals with different diets or digestive systems ... 

Osteoclasts are multinucleated cells derived from pluripotent hematopoietic stem cells. Osteoclasts possess an apical membrane domain, exhibiting a ruffled border that plays a key role in bone resorption (Figure 48-12). A proton-translocating ATPase expels protons across the ruffled border into the resorption area, which is the microenvironment of low pH shown in the figure. This lowers the local pH to 4.0 or less, thus increasing the solubility of hydroxyapatite and allowing demineralization to occur. Lysosomal acid proteases are released that digest the now accessible matrix proteins. 

Figure 48-12. Schematic illustration of some aspects of the role of the osteoclast in bone resorption. Lysosomal enzymes and hydrogen ions are released into the confined microenvironment created by the attachment between bone matrix and the peripheral clear zone of the osteoclast. The acidification of this confined space facilitates the dissolution of calcium phosphate from bone and is the optimal pH for the activity of lysosomal hydrolases. Bone matrix is thus removed, and the products of bone resorption are taken up into the cytoplasm of the osteoclast, probably digested further, and transferred into capillaries. The chemical equation shown in the figure refers to the action of carbonic anhydrase II, described in the text. (Reproduced, with permission, from Jun-queira LC, Carneiro J BasicHistology. Text Atlas, 10th ed. McGraw-Hill, 2003.)...

Metchnikoff (1883) recognized the role of cell types (phagocytes) which were responsible for the engulfinent and digestion of microorganisms. They are a major line of defence against microbes that breach the initial barriers described above. Two types of phagocytic cells are found in the blood, both of which are derived from the totipotent bone marrow stem cell. 

Location Attached to bones openings of some hollow organs (sphincters) Large blood vessels eyes hair follicles Walls of hollow organs of digestive, reproductive, and urinary tracts small blood vessels... 

Generally, tin compounds of 3-4 mgday-1 are ingested in the human body, and are absorbed poorly from the digestive tracts. 40% of the tin are excreted via urine and feces. Tin compounds tend to accumulate in liver, kidney and bone. By the oral route, high levels of tin compounds cause gastrointestinal symptoms such as nausea, vomiting and abdominal pain and headache. 

Open vessel digestion (HN03) for bones, teeth, hair, and soil This is a standard preparation for most organic samples. In the case of soils, nitric acid will not fully dissolve all of the sample, but this method is sufficient to examine the total available elements. 

Closed vessel microwave digestion for bones, teeth, hair, and soil Specially designed closed pressurized Teflon vessels may be used for microwave digestion. Teflon is transparent to microwaves, which enhances the effect of the acids by raising the temperature and pressure within the vessel. In addition the closed vessels will retain any volatile components (e.g., Si) in solution. It must, however, be emphasized that any sealed vessels must only be heated if they have been designed for the purpose. Examples of applications include Kingston and Walter (1992), Baldwin et al. (1994), Sheppard et al. (1994), and Tamba et al. (1994). 

Increasing both dietary Ca and P causes a decrease in PTH-mediated bone resorption polyphosphates and phosphorus in food cause greater reductions than does inorganic orthophosphate, as these sources are slowly released in digestion. 

Bone marrow destruction May lead to death not as lethal as HD Severe discomfort to eyes Permanent corneal damage Harsh respiratory effects Damage to bone marrow Damage to digestive tract and endocrine systems... 

Wu JJ and Eyre DR (1988) Fine powdering exposes the mineral-protected collagen of bone to protease digestion. Calcif Tissue Int 42, 243-247. 

Figure 4.15 k summary of the fate of nucleosides that are produced from RNA digestion in the lumen of the intestine. The nucleosides produced from RNA in the lumen are absorbed by the enterocytes and then transported from the intestine into the blood from where they are taken up by cells (especially proliferating cells, e.g. in the bone marrow) to form nucleotides for DNA and RNA synthesis. (See Chapter 10) NTP is nucleoside triphosphate. 

---