pH as a variable in free zinc ion concentration from zinc-containing lozenges.
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Humans↗
Biomedical subjects
R B Martin
Publications and source records attributed to R B Martin.
Effects of estrogen deficiency on the growth of tissue into porous titanium implants.
The effect of systemic deficiency of estrogen on the growth of tissue into porous titanium-fiber implants was studied in ovariectomized Beagle dogs. Five dogs were ovariectomized and five dogs had a sham operation. After waiting four months to allow the levels of circulating estrogen to decline, a titanium-alloy implant that contained four surface pads of titanium-alloy mesh was implanted in the proximal part of the humerus of each dog bilaterally. Two months later, the implants were harvested and subjected to a mechanical push-out test and quantitative histological study. The push-out strength of the implants from the ovariectomized dogs was 31 per cent less than in the control animals. Ovariectomy caused no difference in the amount of ingrowth of bone but resulted in a significant increase in the amount of fibrous connective tissue within the porous pads. The presence of this fibrous tissue appeared to have an important effect on bone-implant fixation: in the control dogs, strength correlated positively with ingrowth of bone and negatively with ingrowth of fibrous tissue, whereas in the ovariectomized dogs, strength correlated positively with ingrowth of fibrous tissue and not at all with ingrowth of bone.
Animals↗
Promotion of tubulin assembly by aluminum ion in vitro.
It has been proposed that aluminum ion is a contributing factor in a variety of neurological diseases. In many of these diseases, aberrations in the cytoskeleton have been noted. The effects of aluminum ion on the in vitro assembly of tubulin into microtubules has been examined by determining the association constants for the metal ion-guanosine triphosphate-tubulin ternary complex required for polymerization. The association constant for aluminum ion was approximately 10(7) times that of magnesium ion, the physiological mediator of microtubule assembly. In addition, aluminum ion at 4.0 X 10(-10) mole per liter competed effectively with magnesium ion for support of tubulin polymerization when magnesium ion falls below 1.0 millimole per liter. The microtubules produced by aluminum ion were indistinguishable from those produced by magnesium ion when viewed by electron microscopy, and they showed identical critical tubulin concentrations for assembly and sensitivities to cold-induced depolymerization. However, the rate of guanosine triphosphate hydrolysis and the sensitivity to calcium ion-induced depolymerization, critical regulatory processes of microtubules in vivo, were markedly lower for aluminum ion microtubules than for magnesium ion microtubules.
Aluminum↗
Osteonal remodeling in response to screw implantation in canine femora.
We examined the patterns of osteonal remodeling associated with the implantation of a screw in the femoral diaphysis of four mongrel dogs. The dogs were killed at intervals ranging from 11 to 93 days after implantation, and resorption spaces and tetracycline-labeled osteons were counted as functions of postimplant time and distance from the screw. The contralateral femur was used as a control. We found that implantation of the screw initiated a sequence of remodeling activity at the screw site; numerous resorption spaces were observed after 3 weeks, followed by numerous refilling osteons at 7 weeks. When sequential sections along the shaft adjacent to the screw were examined, it appeared that the increased resorption and refilling activity subsequently migrated away from the screw site, both proximally and distally. Also, both the implanted and control femurs exhibited occasional zones along the shaft within which the numbers of labeled osteons were sharply reduced. These "extinction zones" were found to be associated with local maxima in resorption space density. We further noted that the ratio of singly to doubly labeled osteons in the experimental control femurs was high as compared with that in humans, but similar to that previously observed in the canine iliac crest.
Adaptation, Physiological↗
Ovariectomy and trabecular bone remodeling in the dog.
The early effects of ovariectomy (OX) on serum biochemistry and trabecular bone remodeling in the dog were investigated. Adult beagle dams were ovariectomized (n = 8) or sham-ovariectomized (n = 6) and followed for 6 months. All dogs received an iliac crest biopsy at the time of surgery to establish baseline remodeling data. A second contralateral biopsy was obtained at sacrifice. Serum osteocalcin became significantly elevated approximately 8 weeks following OX and remained elevated for the duration of the study. Histomorphometric analysis of serial transilial specimens showed that, at 6 months, OX had significantly increased the rate of bone remodeling in the ilium. Six months following OX in the dog, changes in serum biochemistry and trabecular bone remodeling in the ilium are consistent with those seen in postmenopausal women suffering from "high remodeling osteoporosis".
Animals↗
Effects of ovariectomy in beagle dogs.
Beagle dogs 3-7 years old were ovariectomized (n = 9) or sham operated (n = 6) and followed for 48 weeks with measurements of body weight, tibial shaft bone mineral content (BMC), and serum biochemistry. Following killing, measurements were made of bone strength and histomorphometry. Ovariectomy (OX) significantly reduced serum estrone and estradiol concentrations and their variability from month to month. There was a transient decrease in cortical BMC of the OX dogs during the first 12 postoperative weeks but no difference between the groups after 48 weeks. Serum osteocalcin was elevated, but there was little effect on serum alkaline phosphatase, Ca, P, or calcitonin. OX increased the number of tetracycline-labeled osteons in cortical bone but reduced the percent trabecular surface labeled with tetracycline. OX produced no significant changes in the composition of the bones or loss of cortical area, but a statistically significant 15% trabecular bone loss occurred in the spine. However, bone strength had not been significantly affected at the time of sacrifice.
Animals↗
The stress-moderating effects of weeping and humor.
The moderating effects of emotional weeping and humor on the impact of negative life events were examined. Subjects who reported weeping frequently showed more mood disturbance at high levels of negative events and less to low levels of negative events than those who reported less frequent weeping. Humor-coping buffered stress in all groups except for males who reported frequent crying.
Adaptation, Psychological↗
Fragility and composition of growing rat bone after one week in spaceflight.
To gain some insight into the early effects of spaceflight on skeletal metabolism, we quantified the major chemical constituents and a noncollagenous protein, osteocalcin, in the third-lumbar vertebrae and humeri from 8-wk-old rats that were part of the 7-day NASA Spacelab 3 flight experiments. The ratio of calcium to hydroxyproline in the humeral diaphysis increased from 8.5 in preflight to 9.8 in ground simulation control and only to 8.9 in flight bones. There was no demonstrable change in the fraction of nonmineralized collagen. Osteocalcin content was reduced in the humerus and vertebra. Reduced accumulation of mineral and osteocalcin with no associated decrease in collagen in flight animals suggests that both mineralization and collagen metabolism are impaired in growing animals during spaceflight within a few days after launch. Strength tests of the humeri of flight rats showed substantial deficits that appeared to be related, not only to the reduced bone mass, but also to the composition and quality of new bone formed.
Animals↗
Transferrin binding of Al3+ and Fe3+.
An understanding of Al3+-induced diseases requires identification of the blood carrier of Al3+ to the tissues where Al3+ exerts a toxic action. Quantitative studies demonstrate that the protein transferrin (iron-free) is the strongest Al3+ binder in blood plasma. Under plasma conditions of pH 7.4 and [HCO3-]27 mmol/L, the successive stability constant values for Al3+ binding to transferrin are log K1 = 12.9 and log K2 = 12.3. When the concentration of total Al3+ in plasma is 1 mumol/L, the free Al3+ concentration permitted by transferrin is 10(-14.6) mol/L, less than that allowed by insoluble Al(OH)3, by Al(OH)2H2PO4, or by complexing with citrate. Thus transferrin is the ultimate carrier of Al3+ in the blood. We also used intensity changes produced by metal ion binding to determine the stability constants for Fe3+ binding to transferrin: log K1 = 22.7 and log K2 = 22.1. These constants agree closely with a revision of the reported values obtained by equilibrium dialysis. By comparison with Fe3+ binding, the Al3+ stability constants are weaker than expected; this suggests that the significantly smaller Al3+ ions cannot coordinate to all the transferrin donor atoms available to Fe3+.
Aluminum↗
The addition of tobramycin to contrast bone cement. Effect on flexural strength.
Samples of polymethylmethacrylate (PMMA) bone cement were polymerized in vitro with no additives and with the following additives: methylene blue dye, tobramycin, methylene blue plus tobramycin. After storage for 7 days in saline, samples were tested to failure in three-point bending. Addition of the antibiotic significantly weakened the cement (to 87% of control). However, the combination of tobramycin plus methylene blue was no weaker than tobramycin alone, suggesting that addition of both dye and antibiotic to bone cement is probably a reasonable clinical practice.
Bone Cements↗
Symbiotic Characteristics and Rhizobium Requirements of a Leucaena leucocephala x Leucaena diversifolia Hybrid and Its Parental Genotypes.
In 56-day-old plants, Leucaena leucocephala and its hybrid with L. diversifolia showed 100% more total N than did L. diversifolia. Significant (P < 0.01) host-inoculation interaction in total N was 14.4% of the total phenotypic variation. The most effective and competitive Rhizobium sp. for the leucaenas was TAL 1145. Three-strain mixed inoculation was inferior to TAL 1145 alone.
Journal Article↗
The chemistry of aluminum as related to biology and medicine.
The increasing number of roles discovered for Al3+ in physiological processes demands an understanding of how Al3+ interacts with compounds in biological systems. Al3+ is expected to complex with oxygen donor ligands, especially phosphates, and it does so in soils, in the gastrointestinal tract, and in cells. The stability of Al3+ complexes has generally been misjudged because of lack of recognition that free, aqueous Al3+ is not the dominant form in neutral solutions and that the solubility of Al(OH)3 limits the free Al3+ at the plasma pH 7.4 to less than 10(-11) mol/L. In the presence of inorganic phosphate, the permitted free Al3+ is decreased further, through formation of insoluble aluminum phosphate. This precipitate facilitates the elimination of Al3+ from the body. In contrast, citrate solubilizes Al3+, and an appreciable fraction occurs as a neutral complex that may pass through membranes and provide a vehicle for Al3+ absorption into the body. In the blood plasma the most likely small-molecule complex is that with citrate, while the only competitive protein complex is that with transferrin, a protein built to transport Fe3+ but whose sites are only 30% occupied.
Aluminum↗
An estimation of the equivalent solution dielectric constant in the active-site cavity of metalloenzymes. Dependence of carboxylate-metal-ion complex stabilities on the polarity of mixed aqueous/organic solvents.
The stability constants of the 1:1 complexes between Cu2+ and Zn2+ with formate, acetate and several phenylalkanecarboxylates, i.e. C6H5-(CH2)n-COO- with n = 0 to 5, are summarized for water, 50% aqueous ethanol and 50% aqueous dioxane (I = 0.1 M; 25 degrees C): Complex stability depends upon carboxylate group basicity. The influence of varying amounts of ethanol or dioxane (up to 90%) on the stability of the Cu2+ and Zn2+ (M2+) complexes with formate and acetate (CA) was measured by potentiometric pH titrations. The values for pKHH(CA) and log KMM(CA) increase, as expected, with increasing amounts of the organic solvents, i.e. with decreasing solvent polarity. The changes in the equilibrium constants are also evaluated with regard to the mole fractions of the organic solvents and the corresponding dielectric constants. These results may be used to estimate for low dielectric cavities in proteins the equivalent solution dielectric constant on the basis of enhanced carboxylate basicity or metal ion binding capability (method 1). Furthermore, the measured stability constants are used for comparisons of the coordination tendency of carboxylate ligands towards zinc(II)-metalloenzymes (method 2); in this way the equivalent solution dielectric constants in the active-site cavities of bovine carbonic anhydrase and carboxypeptidase A are estimated: the values are of the order of 35 and 70, respectively. This method seems to be generally applicable to metalloproteins.
Binding Sites↗
Effects of age and sex on the amount and distribution of mineral in Eskimo tibiae.
The bone mineral content (BMC), bone width, and cross-sectional moment of inertia (CSMI) of 141 Alaskan Eskimo tibias were measured using photon absorptiometry. The effects of age and sex on the bones' structural properties were studied. It was found that in women, BMC decreased by 50% between the third and sixth decades, but that of the males did not decline significantly with age. This was true of the CSMI as well, for bending in both the anteroposterior (AP) and mediolateral (ML) planes. This result is different than that in some other prehistoric native American populations, where tibia CSMI increases with age in both sexes. The CSMI values were significantly higher in men than in women. Also, in men the AP CSMI was 55% larger than the ML CSMI; in women this difference was only 25%, and declined with age. Since the tibia is preferentially loaded in the AP plane by locomotor activities, the platycnemic differences between the sexes may reflect sex-related differences in activity which become more pronounced with age. The non-destructive method for obtaining data on the cross-sectional geometry of dry bones which is described here may be useful in studying other archaeological collections.
Adult↗
Bone remodeling in response to in vivo fatigue microdamage.
It has been suggested that osteonal remodeling is triggered by bone microdamage. The validity of this theory rests on the assumption that loading within the physiological range will produce substantial microdamage with relatively few load cycles. The object of the first experiment was to determine threshold values required to consistently produce fatigue microdamage in vivo. The left forelimb of five groups of dogs, characterized by different strain levels and different numbers of load cycles, were loaded in three point bending. The number of microscopic fields which contained some microdamage was calculated as a percentage of the total number of fields. This experiment indicated that loads producing strains as low as 1500 microstrain on the radius and 1400 microstrain on the ulna for 10,000 cycles will produce significant bone microdamage. A second experiment was performed to verify this threshold and to determine whether microcracks are associated with the initiation of bone remodeling. Procedures in this experiment were the same as those in the first, except that all dogs were loaded in such a way as to produce strains on the radius of 1500 microstrain for 10,000 cycles, and the dogs were sacrificed 1-4 days after loading. The loaded limb demonstrated significantly more microdamage than the control limb (p = 0.03). Moreover, we observed 44 times as many microcracks in association with resorption spaces as expected by chance alone. These data support the hypothesis that fatigue microdamage is a significant factor in the initiation of intracortical bone remodeling.
Animals↗
Osteocalcin as an indicator of bone metabolism during spaceflight.
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Animals↗
Senile osteoporosis. The effects of exercise.
The available literature indicates that a high level of physical activity throughout life can result in increased skeletal mass during the fourth decade. Such a large reservoir of bone mass at midlife may delay the clinical manifestations of osteoporosis in later life. Furthermore, the published studies of animal models and humans strongly suggest that physical activity retards or prevents involutional bone loss in both recently postmenopausal and very elderly women.
Adult↗
Effects of mechanical loading on the tissues of the rabbit knee.
We studied changes in subchondral bone and articular cartilage in an animal model of osteoarthrosis. In this model we applied repetitive impulsive loads to rabbits' knees. Their legs were held in short leg splints so the rabbits were unable to dampen the peak applied load with ankle flexion. After sacrifice, at 1 day to 6 weeks, we studied proximal tibial load-bearing cartilage histologically, biochemically, and with radioactive sulfate uptake. We also studied the subchondral bone under that cartilage histologically, histomorphometrically, with bone scan (99mTc pyrophosphate), and by tetracycline labeling. An increase in 99mTc labeling of the subchondral bone was the first reliable change observed. This was followed by an increase in tetracycline labeling, bone formation, and a decrease in porosity, which has been associated with relative stiffening of bone. Horizontal splitting and deep fibrillation of the overlying articular cartilage followed the early bone changes. All of these changes preceded changes in content and characterization of cartilage proteoglycans or increased chondrocyte activity as manifested by incorporation of radioactive sulfate. In this model the early bone changes preceded changes in the articular cartilage. The deep splitting of articular cartilage occurred prior to metabolic alteration of that tissue.
Animals↗