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Biomedical subjects

I A Silver

Publications and source records attributed to I A Silver.

At least 91 records · Page 5Linked to original sources
PubMed1981

Synaptosomes from rat brain: morphology, compartmentation, and transmembrane pH and electrical gradients.

Morphological studies of synaptosomes isolated from rat brains show that approximately 68% of the synaptosomes in these preparations contain synaptic vesicles (range, 62--72.5%). Approximately 30% of the synaptosomes contain mitochondria, and only less than 20% of the total mitochondria in good preparations are free and not enclosed in synaptic structures. The mitochondrial volume percent calculated on the basis of the measured cytochrome c content is 5% for synaptosomes isolated from anesthetized animals and 11% for synaptosomes isolated from unanesthetized animals. These numbers bracket the value of 8.7% obtained from electron micrographs. The volume percent of intrasynaptic vesicles is 1.5% as calculated from electron micrographs. The pH gradient between the extracellular pH and the mean intracellular pH is --0.45, as measured by equilibrium distributions of methylamine and dimethylamine, and --0.05, as determined by equilibrium distributions of 5,5-dimethyloxazolidine-2,4-dione and trimethylacetic acid. Analysis of these data shows that there cannot be a large pH gradient (alkaline inside) across the mitochondria, nor can the synaptic vesicle compartment be very large (less than 1.85%). Equilibrium distribution of [3H]triphenylmethylphosphonium ion in synaptosomal preparations gives a calculated apparent potential of --85 mV, in agreement with our previous value. Analysis of these data using the measured volumes of mitochondrial and intrasynaptic vesicular compartments (8.7 and 1.5%, respectively) gives a maximum possible transmitochondrial membrane potential of --59 mV.

Animals↗
PubMed1981

The actual cautery -- myth and reality in the art of firing.

The historical development of "firing" as a treatment for various complaints in animals and man is followed from the first surviving written account by Vegetius (approximately AD 500) to the present day. Changing concepts as to the mechanism of action of the actual cautery are examined in relation to physiological understanding at various times and conflicting views and evident fallacies are discussed. It is of particular interest that firing of "sinewes" (tendons and ligaments) was expressly forbidden until the 18th century. It is concluded that "firing" is an outmoded practice for which there is no scientific justification.

Animals↗
PubMed1981

Regulation of wound-healing angiogenesis-effect of oxygen gradients and inspired oxygen concentration.

Tissue hypoxia is a well-known stimulus to angiogenesis. The central dead space in healing wounds has been shown to be hypoxic (PO2 = 1 to 10). Angiogenesis is a necessary component of all healing wounds. Rabbit ear chambers were used to explore the contribution of O2 gradients and various inspired oxygen concentrations on wound healing and angiogenesis. These experiments demonstrate that: (1) A hypoxic tissue gradient is mandatory for wound-healing angiogenesis, (2) when the hypoxic gradient is destroyed capillary growth cases, and (3) inspired oxygen concentrations affect the rate and density of capillary growth.

Animals↗
PubMed1981

Early cellular responses in vitro to endotoxin administration.

The sequence of early events which follow the administration of E coli lipopolysaccharide (LPS) to cultured mouse neuroblastoma (C-1300) cells was investigated. Emphasis was placed on cellular energy metabolism in order to establish whether or not an energy failure occurred and whether it was a primary or a secondary effect. Exposure of cultured neuroblastoma cells to LPS produced rapid changes in the regulatory parameters of energy metabolism, an oxidation of intramitochondrial pyridine nucleotides, and a decline in cellular [ATP]/[ADP] [Pi], which were followed by alterations in mitochondrial morphology. In spite of the changes in individual parameters at early stages of exposure to LPS, the cellular energy producing systems remained tightly controlled and the rate of ATP synthesis was maintained at a constant and undiminished level. This allowed the cells to preserve their ionic gradients as manifested by high intracellular [K+] and unaltered transmembrane electrical and pH gradients. These early changes in mitochondrial metabolism were not accompanied by detectable leakage of mitochondrial matrix enzymes into the cytosol, which indicated that mitochondrial membrane remained intact. After longer exposure to LPS, the rate of ATP synthesis declined, the mitochondrial membrane became permeable to high molecular weight substances (matrix enzymes), and intracellular [K+] began to decrease (K+ leakage). It was concluded that responses of mitochondrial metabolism are one of the early events in endotoxemia.

Adenosine Diphosphate↗
PubMed1981

Collagen degradation in an experimental inflammatory lesion: studies on the role of the macrophage.

Collagen degradation was investigated in experimental inflammatory lesions made by implanting fluorescein-collagen sponges into sensitised rats for four days, before transferring them into culture medium. The breakdown of the collagenous structure in vitro by invading cells was inhibited by steroids and related anti-inflammatory drugs whereas non-steroidal anti-inflammatory drugs were without effect. Inhibitors of the lysosomal proteinases were variably effective with chloroquine giving total inhibition, leupeptin and TLCK partial inhibition and aurothioglucose showing no effect. Histochemical studies were made of the distribution of cathepsin B. Beta-glucuronidase and N-acetyl-glucosaminidase in macrophages attached to a collagen substratum. Measurements with specific microelectrodes showed that the microenvironment at the surface of activated macrophages was markedly acidic with values of pH less than 5 between attached cells and collagen substratum. Such conditions would be hostile to neutral collagenases and favour acid (lysosomal) proteinases.

Acetylglucosaminidase↗
PubMed1980

An assessment of filamentous carbon fibre for the treatment of tendon injury in the horse.

The results of an assessment of carbon fibre for biological use are given, with particular reference to the clinical use of the material in the treatment of equine tendon injury. Biocompatability of the fibres is assessed using fibroblast cell cultures and replacement of normal tendon with carbon fibre prostheses in experimental animals. The rationale and technique for using this material in clinical cases of tendon injury in the racehorse are described. Results are given from 62 implant operations in a limited series of 40 horses.

Achilles Tendon↗
PubMed1979

Cellular energy metabolism, trans-plasma and trans-mitochondrial membrane potentials, and pH gradients in mouse neuroblastoma.

A method for quantitative evaluation of transmembrane electrical potential and pH gradients across a subcellular compartment in an intact cell is presented. This approach has been applied in studies of mouse neuroblastoma C-1300 clone NB41A3, in which the transmembrane electrical potential and pH gradients and the mitochondrial volume percent have been determined. Membrane potentials and pH gradients were measured by two different methods. Equilibrium distributions of [(3)H]triphenylmethyl phosphonium and [(14)C]-thiocyanate ions gave calculated apparent membrane potentials of -77.0 and -29.6 mV, respectively, at 20-25 degrees C; a value of -60.8 mV was obtained from microelectrode measurements. Equilibrium distributions of weak acids ([(14)C]trimethylacetic acid and 5,5-di[(14)C]methyl-2,4-oxazolidine-dione) and of weak bases ([(14)C]dimethylamine and [(14)C]trimethylamine) gave calculated upper and lower limits of the pH gradient (Delta pH = pH(e) - pH(i)) of -0.14 and -0.21 pH unit, respectively. The microelectrode measurements showed that the intracellular pH is within 0.1 of a pH unit or less of the extracellular pH over the extracellular pH range of 7.35-6.85. The mitochondrial volume percent calculated on the basis of the measured cytochrome c content is 5.6 +/- 1.2% and compares well with estimates of 5.4 +/- 1.1% obtained from 25 electron micrographs. Measurements of the cellular energetic parameters gave values within the range found in other cells and perfused organs. Comparison of the results of the microelectrode and equilibrium measurements permits estimates of the electrical potential and pH gradients across the mitochondrial membrane (mitochondria-to-cytoplasm gradients) to be made and suggests that the trans-mitochondrial membrane protonmotive force in the intact cell cannot be greater than -143 mV.

Animals↗
PubMed1979

The mechanics of wound healing.

This paper discusses the factors which affect the healing of wounds at the tissue and organ levels. It covers some of the problems which complicate the sequence of healing and considers the mechanisms involved in regeneration and repair of tissues. The factors associated with the stimulus and sequence of healing and their interactions are also reviewed.

Animals↗
PubMed1979

Mechanism of the cerebrocortical vasodilatation during anoxia.

The possible role of cerebrocortical ion homeostasis, NAD/NADH redox state and of cortical oxygen tension was investigated in the initiation of hypoxic cortical vasodilatation. In addition, changes in cerebrocortical extracellular concentrations of Na+, K+, and Cl- during anoxia were studied. The results were as follows. a) The cerebrocortical reflectance decrease, e.g. cerebral vasodilatation, lagged behind the cortical pO2 decrease by 1-2 sec, but preceded the decrease of arterial blood pressure and ECoG as well as the extracellular Na+, K+, Cl- increases by 20-30 sec. Since the cortical pO2 decreased first and the ion changes lagged behind the onset of vasodilatation by 20-30 sec, it is suggested that the CBF increase in hypoxia is mediated via the cortical pO2 decrease. b) A significant NAD reduction was already present after 20 sec. of nitrogen breathing. Since the ECoG and MABP decreased, and K+ activity increased much later than this, it is presumed that the NAD reduction during the first 30-40 sec of anoxia indicates an increased rate of glycolysis, but not mitochondrial hypoxia. c) In the predepolarization phase a 17% K+, 4% Na+, 5% Cl- increase is probably the result of a reduction of the extracellular spaces caused by water movement and by the migration of Na+ and Cl- from the extracellular to the intracellular space. The large K+, Na+, Cl- changes during terminal depolarization can be interpreted as a result of the failure of the membrane bound Na+ -K+ pump and of the altered ion permeability of the cell membranes.

Action Potentials↗
PubMed1979

Effect of arterial hypoxia on the cerebrocortical redox state, vascular volume, oxygen tension, electrical activity and potassium ion concentration.

The effect of different degrees of arterial hypoxia on cerebrocortical NAD/NADH redox state, reflectance, oxygen tension, extracellular potassium ion concentration, ECoG and arterial blood pressure was investigated in rats. The results may be summarized as follows. a) The decrease of cortical pO2 preceded the dilatation of cortical vessels by 15-20 sec but the changes in cortical extracellular potassium ion concentration, ECoG and arterial blood pressure started later than the vasodilatation. These results give further support to the regulatory role of cortical pO2 decrease in the initiation of cerebrocortical vasodilatation during arterial hypoxia. b) Since the K+ concentration of the brain cortex and the ECoG did not change in mild arterial hypoxia, the significant NAD reduction obtained in this experimental group is likely to be of cytoplasmic origin. The same conclusion applies to the initial periods of severe arterial hypoxia. On the basis of the extent of NAD reduction during various degrees of arterial hypoxia it is concluded that about 30% of the NAD reduction occurring in anoxia is of cytoplasmic origin. c) When the animals were ventilated with a gas mixture containing 4-7% oxygen, the brain cortex became nearly anoxic, partly because of the gradual decrease of arterial blood pressure. Finally, the mechanism of potassium leakage is identical under prolonged severe arterial hypoxaemia and on anoxic terminal depolarization.

Action Potentials↗
PubMed1979

The significance of clinical assessment of brain tissue oxygenation in different pathological conditions: an overview.

The development of methods of measurement of brain oxygenation in man is reviewed and the possible clinical potential of some new and established laboratory techniques is evaluated. Advantages and problems associated with the various approaches are considered together with the difficulties that are encountered in interpretation of data obtained and the factors that may increase such difficulties. It is concluded that invasive techniques that can only be used intraoperatively are of limited value but may be helpful in confirming the edges of ischemic areas or the restoration of adequate local blood flow. Chronically implanted devices have been useful in detecting epileptic foci and in evaluation of anesthetic regimes in patients with brain lesions. Infrared spectroscopy may offer possibilities for noninvasive whole brain monitoring in patients, but the method lacks resolution.

Brain↗
PubMed1979

Resorption of insoluble, heterologous, fluorescein-collagen sponges in sensitized and non-sensitized rats.

Sponges of insoluble bovine collagen were slowly resorbed over a 35-day period when implanted under the back skin of rats. The cellular picture was typical of a mild foreign-body reaction. The reaction to fluorescein-labelled collagen sponges was similar but there was evidence also of a weak immunological response. An acute inflammatory reaction with massive oedema was elicited when fluorescein-labelled collagen sponges were implanted in rats previously sensitized to either fluorescein-collagen or fluorescein-bovine serum albumin. The early invasion by PMN leucocytes subsided after 4 days and caused no observable breakdown of the sponge. The implanted material was rapidly encapsulated by fibrous tissue which was then resorbed along with the sponge between the 7th and 12th day. Macrophages were very active in the sponge at this time, sometimes forming giant cells. Fibroblasts were invading from the periphery with the development of the granulation tissue. The small residue which remained after this time was overrun by granulation tissue and was slowly resorbed up to the 35th day. Throughout the period of study there was only a weak local immunological response after the 28th day. The level of circulating antibodies against the fluorescein hapten was high, but the titre for the antibodies against bovine collagen remained low. The significance of these findings in the pathological destruction of connective tissue is discussed.

Absorption↗