Use of carbon fibre for tendon repair.
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Biomedical subjects
Publications and source records attributed to I A Silver.
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The investigation was designed to identify microenvironmental factors that might be important in the regulation of local blood flow. Cellular microenvironment in terms of Po2, pH, [K+], [Cl-], [Ca2+] and lactate was measured in rat brain by means of specific microelectrodes. Vascular endothelium was stained in vivo with Thioflavine S. Local blood flow was measured with micro hydrogen electrodes. Some intracellular measurements of pH were made in conjunction with extracellular measurements. The main findings were that local autoregulation responses and blood flow changes in response to imposed hypoxic changes were very rapid (1-1.5 s). Microflow responses to changes in local cell activity were limited to a region not more than 250 micron in diameter. Increased blood flow in acute hypoxia occurred within 1-2 s of the fall in tissue Po2 and was much more rapid than changes in either pH or potassium. Intracellular pH changed within 10 s of the onset of severe hypoxia but in all cases the blood flow followed the Po2 much more closely than any other parameter. It is suggested that changes in capillary endothelium and local membrane transmission may play a part in autoregulatory mechanisms.
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Simultaneous measurements of the mitochondrial [NAD+]/[NADH], the cytoplasmic [ATP]/[ADP] x [Pi], and the respiratory rate were carried out in suspensions of cultured kidney cells in a range of defined oxygen tensions. The results show that as the extracellular oxygen concentration falls there is a decrease in the respiratory rate, which is accompanied by a decrease in the [ATP]/[ADP] and a progressive reduction of cytochrome c. Even at low O2 tensions the mitochondrial respiratory chain between the NAD couple and cytochrome c remains at near equilibrium with the ATP synthesizing reactions. It is concluded that limited oxygen supply affects cellular metabolism at much higher concentrations than the P50 value for the oxygen dependence of respiration, but the respiratory rate remains relatively unchanged due to compensatory changes in the [ATP]/[ADP] X [Pi] and progressive reduction of cytochrome c. These metabolic changes may form a basis for the phenomenon of tissue oxygen sensing at near physiological oxygen tensions.
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Measurement of the PO2 in the mucosal cells and at various depths of the lamina propria lining the nasal cavity in five male goats using Silver's special microelectrodes, revealed relative hypoxia in the anterodorsal part of the nasal septum and tips of naso- and maxilloturbinals. In these sites PO2 values varied between 55-65 at the surface and 30-35 in the superficial subepithlial layer while elsewhere in the nose, lip and tongue, PO2 values of 85-90 were obtained. Temperature measurements with the thermistor in two goats yielded readings of 34-34-5 degrees C. in the hypoxic areas against 36-37 degrees C. in the posterior parts, the roof and floor of the nasal cavity. However, the oxygen tension diminished steadily in all areas as the microneedle electrode approached the chondro-osteal tissues but PO2 values of 0-10 in the perichondrium. The significance of these findings in the predilective localization of granulomata and various forms of vasculitis in the anterior endonasal tissues has been discussed.
The development of ion selective microelectrodes has made it possible to measure the normal steady state in the pericellular environment together with ion fluxes in response to physiological or pathological disturbances. Combined intracellular and extracellular measurements indicate that there is a considerable range of ability between various types of cells in the efficiency with which they can tolerate changes in pericellular conditions. Macrophages are extremely tolerant while cells of the cerebral cortex require a very finely controlled local environment. Combination of ion selective probes with microelectrodes which measure substrate and oxygen availability extend the information which can be obtained about ionic composition of cellular environment and the factors which are important in its homostasis.
A new method has been developed for the determination of maximal reduction of NAD in the rat cerebral cortex. NADH fluorescence (450 nm) induced by 366-nm light and UV reflectance were measured by a time-sharing light pipe fluorometer. The redox state of the cortical surface was altered by perfusion of oxygen or carbon monoxide through a Teflon chamber adjacent to the dura. This study examines changes caused by local perfusion with the two gases in normoxia, hypoxia, and anoxia. Alternation of topical carbon monoxide and oxygen becomes effective in altering the intracellular redox state at 15% inspired oxygen and caused 20% changes at zero inspired oxygen. Conversely, topical application of oxygen to the systemically anoxic tissue causes oxidation of reduced NAPH in the cells within the field of fluorometric observation equivalent to that caused by breathing approximately 8% oxygen systemically.
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