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Biomedical subjects

S A Bloomfield

Publications and source records attributed to S A Bloomfield.

At least 19 recordsLinked to original sources
PubMed2005

Effects of eccentric exercise training on cortical bone and muscle strength in the estrogen-deficient mouse.

The purpose of this study was to determine whether eccentrically biased exercise training could attenuate changes in muscle and bone function associated with estrogen deficiency in the mouse model. Four groups of ICR mice were used: control (Con), sham ovariectomized (Sham), ovariectomized (OVX), and ovariectomized + high-force resistance training (OVX+Train). All groups except Con were implanted with a nerve cuff surrounding the peroneal nerve to stimulate the left ankle dorsiflexors. Training consisted of 30 stimulated eccentric contractions of the left ankle dorsiflexors at approximately 150% of peak isometric torque every third day for 8 wk. After the training period, groups were not significantly different with regard to peak torque or muscle size. However, the tibial midshaft of the trained leg in the OVX+Train mice exhibited greater stiffness (+15%) than that in the untrained OVX mice, which could not be explained by changes in cross-sectional geometry of the tibia. Scaling of bone mechanical properties to muscle strength were not altered by ovariectomy or training. These data indicate that eccentric exercise training in adult mice can significantly increase bone stiffness, despite the absence of ovarian hormones.

Animals↗
PubMed2004

Functional recovery of the plantarflexor muscle group after hindlimb unloading in the rat.

Research into skeletal muscle's response to hindlimb unloading (HU) of the rodent has focused on that of the markedly affected slow-twitch anti-gravity muscles (e.g., soleus). However, the ability of the animal to locomote following HU should be best determined by the in vivo functional properties of the muscle groups involved and, to our knowledge, this has not been investigated. Our objective was to determine how the in vivo functional properties of the rat ankle plantarflexor group change after 28 days of HU and during a subsequent 28-day recovery. Rats ( n=48) were unloaded for 28 days after which they were either tested immediately or allowed to recover for 7, 14, or 28 days before being tested. Control rats ( n=61) were tested at comparable times. In vivo functional properties of the ankle plantarflexors were assessed under anesthesia using an isokinetic dynamometer and included determination of the isometric torque-frequency relationship, the concentric torque-ankle angular velocity relationship, and fatigability. Immediately after HU, plantarflexor muscle weight was reduced by 24% but isometric torque production was reduced by 7-9% only at > or =100 Hz and concentric torque production was not significantly affected. However, after 7 days of recovery, in vivo function was more adversely affected; isometric and concentric torques were reduced by 12-33% and 16-36%, respectively, relative to control levels. In vivo plantarflexor function was recovered by 14 days. In conclusion, 28 days of HU has minor adverse effects on the in vivo function of the rat ankle plantarflexors. During the first week of recovery from HU, injury apparently occurs to the plantarflexors resulting in a transient impairment of functional capacity.

Animals↗
PubMed2002

Site- and compartment-specific changes in bone with hindlimb unloading in mature adult rats.

The purpose of this study was to examine site- and compartment-specific changes in bone induced by hindlimb unloading (HU) in the mature adult male rat (6 months old). Tibiae, femora, and humeri were removed after 14, 21, and 28 days of HU for determination of bone mineral density (BMD) and geometry by peripheral quantitative computed tomography (pQCT), mechanical properties, and bone formation rate (BFR), and compared with baseline (0 day) and aging (28 day) controls. HU resulted in 20%-21% declines in cancellous BMD at the proximal tibia and femoral neck after 28 day HU vs. 0 day controls (CON). Cortical shell BMD at these sites was greater (by 4%-6%) in both 28 day HU and 28 day CON vs. 0 day CON animals, and nearly identical to that gain seen in the weight-bearing humerus. Mechanical properties at the proximal tibia exhibited a nonsignificant decline after HU vs. those of 0 day CON rats. At the femoral neck, a 10% decrement was noted in ultimate load in 28 day HU rats vs. 28 day CON animals. Middiaphyseal tibial bone increased slightly in density and area during HU; no differences in structural and material properties between 28 day HU and 28 day CON rats were noted. BFR at the tibial midshaft was significantly lower (by 90%) after 21 day HU vs. 0 day CON; this decline was maintained throughout 28 day HU. These results suggest there are compartment-specific differences in the mature adult skeletal response to hindlimb unloading, and that the major impact over 28 days of unloading is on cancellous bone sites. Given the sharp decline in BFR for midshaft cortical bone, it appears likely that deficits in BMD, area, or mechanical properties would develop with longer duration unloading.

Aging↗
PubMed2001

Morphology and physiology of the polyaxonal amacrine cells in the rabbit retina.

We examined the morphology and physiological response properties of the axon-bearing, long-range amacrine cells in the rabbit retina. These so-called polyaxonal amacrine cells all displayed two distinct systems of processes: (1) a dendritic field composed of highly branched and relatively thick processes and (2) a more extended, often sparsely branched axonal arbor derived from multiple thin axons emitted from the soma or dendritic branches. However, we distinguished six morphological types of polyaxonal cells based on differences in the fine details of their soma/dendritic/axonal architecture, level of stratification within the inner plexiform layer (IPL), and tracer coupling patterns. These morphological types also showed clear differences in their light-evoked response activity. Three of the polyaxonal amacrine cell types showed on-off responses, whereas the remaining cells showed on-center responses; we did not encounter polyaxonal cells with off-center physiology. Polyaxonal cells respected the on/off sublamination scheme in that on-off cells maintained dendritic/axonal processes in both sublamina a and b of the IPL, whereas processes of on-center cells were restricted to sublamina b. All polyaxonal amacrine cell types displayed large somatic action potentials, but we found no evidence for low-amplitude dendritic spikes that have been reported for other classes of amacrine cell. The center-receptive fields of the polyaxonal cells were comparable to the diameter of their respective dendritic arbors and, thus, were significantly smaller than their extensive axonal fields. This correspondence between receptive and dendritic field size was seen even for cells showing extensive homotypic and/or heterotypic tracer coupling to neighboring neurons. These data suggest that all polyaxonal amacrine cells are polarized functionally into receptive dendritic and transmitting axonal zones.

Amacrine Cells↗
PubMed2001

Rod vision: pathways and processing in the mammalian retina.

Bipolar cells in the mammalian retina are postsynaptic to either rod or cone photoreceptors, thereby segregating their respective signals into parallel vertical streams. In contrast to the cone pathways, only one type of rod bipolar cell exists, apparently limiting the routes available for the propagation of rod signals. However, due to numerous interactions between the rod and cone circuitry, there is now strong evidence for the existence of up to three different pathways for the transmission of scotopic visual information. Here we survey work over the last decade or so that have defined the structure and function of the interneurons subserving the rod pathways in the mammalian retina. We have focused on: (1) the synaptic ultrastructure of the interneurons; (2) their light-evoked physiologies; (3) localization of specific transmitter receptor subtypes; (4) plasticity of gap junctions related to changes in adaptational state; and (5) the functional implications of the existence of multiple rod pathways. Special emphasis has been placed on defining the circuits underlying the different response components of the AII amacrine cell, a central element in the transmission of scotopic signals.

Animals↗
PubMed2001

Cellular and molecular mechanisms for the bone response to mechanical loading.

To define the cellular and molecular mechanisms for the osteogenic response of bone to increased loading, several key steps must be defined: sensing of the mechanical signal by cells in bone, transduction of the mechanical signal to a biochemical one, and transmission of that biochemical signal to effector cells. Osteocytes are likely to serve as sensors of loading, probably via interstitial fluid flow produced during loading. Evidence is presented for the role of integrins, the cell's actin cytoskeleton, G proteins, and various intracellular signaling pathways in transducing that mechanical signal to a biochemical one. Nitric oxide, prostaglandins, and insulin-like growth factors all play important roles in these pathways. There is growing evidence for modulation of these mechanotransduction steps by endocrine factors, particularly parathyroid hormone and estrogen. The efficiency of this process is also impaired in the aged animal, yet what remains undefined is at what step mechanotransduction is affected.

Animals↗
PubMed2000

A flattened retina-eyecup preparation suitable for electrophysiological studies of neurons visualized with trans-scleral infrared illumination.

We present an in vitro flattened retinal-scleral preparation suitable for electrophysiological studies from visually targeted amacrine and ganglion cells of the rabbit retina. In a newly designed superfusion chamber, the retinal-scleral tissue is stained with Azure B allowing for imaging of neurons in the ganglion cell layer with an infrared (IR)-sensitive CCD camera via trans-scleral IR illumination. Neurons can be visually identified and targeted for both extracellular and intracellular recordings made singly or in simultaneous pairs. The quality and stability of the recordings are excellent and the tissue remains viable for up to 10 h. This relatively simple preparation avoids the extensive surgical manipulations inherent to those based on isolated retinas or retinal slices. Moreover, the use of trans-scleral IR illumination rather than fluorescent dyes to visualize and target neurons allows for electrophysiological studies of the retina under controlled adaptational states including dark-adapted conditions.

Action Potentials↗
PubMed2000

Surround inhibition of mammalian AII amacrine cells is generated in the proximal retina.

1. Intracellular recordings were obtained from neurons in the superfused retina-eyecup preparation of the rabbit under dark-adapted conditions. Neurotransmitter agonists and antagonists were applied exogenously via the superfusate to dissect the synaptic pathways pharmacologically and thereby determine those pathways responsible for the generation of the on-centre/off-surround receptive fields of AII amacrine cells. 2. Application of the metabotropic glutamate receptor agonist, APB, reversibly blocked both the on-centre and off-surround responses of AII cells. These data were consistent with the idea that both the centre- and surround-mediated responses are derived from inputs from the presynaptic rod bipolar cells. 3. Whereas rod bipolar cells showed on-receptive fields approximately 100 microm across, we found no evidence for an antagonistic off-surround response using light stimuli which effectively elicited the off-surrounds of AII amacrine cells. These results indicated that the surrounds of AII cells are not derived from rod bipolar cell inputs. 4. Application of the ionotropic glutamate receptor antagonists CNQX or DNQX enhanced the on-centre responses of AII cells but attenuated the off-surround responses. These data indicated that the centre- and surround-mediated responses could not both be derived from signals crossing the rod bipolar-to-AII cell synapse. 5. Application of the glycine antagonist, strychnine, had only minor and variable effects on AII cell responses. However, the GABA antagonists picrotoxin and bicuculline enhanced the on-centre response but attenuated or completely blocked the off-surround response of AII cells. The GABA antagonists had no effect on the responses of horizontal cells indicating that their effects on AII cell responses reflected actions on inner retinal circuitry rather than feedback circuitry in the outer plexiform layer. 6. Application of the voltage-gated sodium channel blocker TTX enhanced the on-centre responses of AII cells but attenuated or abolished their off-surround responses. 7. Taken together, our results suggest that the on-centre responses of AII cells result from the major excitatory drive from rod bipolar cells. However, the surround receptive fields of AII cells appear to be generated by lateral, inhibitory signals derived from neighbouring GABAergic, on-centre amacrine cells. A model is presented whereby the S1 amacrine cells produce the surround receptive fields of AII amacrine cells via inhibitory, feedback circuitry to the axon terminals of rod bipolar cells.

Aminobutyrates↗
PubMed2000

Alterations in skeletal perfusion with simulated microgravity: a possible mechanism for bone remodeling.

Bone loss occurs as a consequence of exposure to microgravity. Using the hindlimb-unloaded rat to model spaceflight, this study had as its purpose to determine whether skeletal unloading and cephalic fluid shifts alter bone blood flow. We hypothesized that perfusion would be diminished in the hindlimb bones and increased in skeletal structures of the forelimbs and head. Using radiolabeled microspheres, we measured skeletal perfusion during control standing and after 10 min, 7 days, and 28 days of hindlimb unloading (HU). Femoral and tibial perfusion were reduced with 10 min of HU, and blood flow to the femoral shaft and marrow were further diminished with 28 days of HU. Correspondingly, the mass of femora (-11%, P < 0. 05) and tibiae (-6%, P < 0.1) was lowered with 28 days of HU. In contrast, blood flow to the skull, mandible, clavicle, and humerus was increased with 10 min HU but returned to control levels with 7 days HU. Mandibular (+10%, P < 0.05), clavicular (+18%, P < 0.05), and humeral (+8%, P < 0.1) mass was increased with chronic HU. The data demonstrate that simulated microgravity alters bone perfusion and that such alterations correspond to unloading-induced changes in bone mass. These results support the hypothesis that alterations in bone blood flow provide a stimulus for bone remodeling during periods of microgravity.

Animals↗
PubMed1999

Dark- and light-induced changes in coupling between horizontal cells in mammalian retina.

Retinal horizontal cells exhibit large receptive fields derived from their extensive electrical coupling by means of gap junctions. The conductance of these gap junctions seems to be regulated by dopamine acting through a cAMP-mediated cascade. There is now abundant evidence that extracellular dopamine levels vary with changes in ambient light intensity, suggesting that changes in the dark/light adaptational state of the retina can modulate coupling between horizontal cells. We studied this question in the mammalian retina by determining the effects of ambient light levels, in the form of changing background light intensity, on the coupling profiles of A- and B-type horizontal cells in the rabbit. Changes in coupling were assessed by measurements of the space constants of the syncytium formed by horizontal cells and the intercellular spread of the biotinylated tracer Neurobiotin. Our results indicate that dark-adapted horizontal cells show relatively weak coupling. However, presentation of background lights as dim as one-quarter log unit above rod threshold resulted in increases in both the averaged extent of tracer coupling and space constants of A- and B-type horizontal cells. Coupling expanded further as background light intensities were increased by 1-1.5 log units, after which additional light adaptation brought about an uncoupling of cells. Coupling reached its minimum at light intensities about 3 log units above rod threshold, after which, with further light adaptation, it stabilized at levels close to those seen in dark-adapted retinas. Our results indicate that electrical coupling between mammalian horizontal cells is modulated dramatically by changes in the adaptational state of the retina: coupling is maximized under dim ambient light conditions and diminishes as the retina is dark or light adapted from this level.

Adaptation, Ocular↗
PubMed1999

Mechanical loading attenuates bone loss due to immobilization and calcium deficiency.

Our purpose was to determine the effects of a mechanical loading intervention on mass, geometry, and strength of rat cortical bone during a period of disuse concurrent with calcium deficiency (CD). Adult female rats were assigned to unilateral hindlimb immobilization, immobilized-loaded, or control (standard chow, 1.85% calcium) treatments. Both immobilized groups were fed a CD rat chow (0.01% calcium) to induce high bone turnover. Three times weekly, immobilized-loaded rats were subjected to 36 cycles of 4-point bending of the immobilized lower leg. After 6 wk, the immobilized rats exhibited decreased tibial shaft bone mineral density (-12%), ultimate load (-19%), and stiffness (-20%; tested in 3-point bending to failure) vs. control rats. Loading prevented this decline in bone density and attenuated decreases in ultimate load and stiffness. Elastic modulus was unaffected by disuse or loading. Bone cross-sectional area in the immobilized-loaded rats was equivalent to that of control animals, even though endocortical resorption continued unabated. On the medial periosteum, percent mineralizing surface doubled vs. that in immobilized rats. This loading regimen stimulated periosteal mineralization and maintained bone mineral density, thereby attenuating the loss in bone strength incurred with disuse and concurrent calcium deficiency.

Animals↗
PubMed1998

Effects of ethanol on gene expression in rat bone: transient dose-dependent changes in mRNA levels for matrix proteins, skeletal growth factors, and cytokines are followed by reductions in bone formation.

Several studies were performed in female rats to determine dose and time course changes in mRNA levels for matrix proteins in bone after a single administration of ethanol. As expected, dose-dependent transient increases in blood ethanol were measured. Additionally, there was mild hypocalcemia with no change in immunoreactive parathyroid hormone. Coordinated dose-dependent increases in mRNA for type 1 collagen, osteonectin, and osteocalcin were noted in the proximal tibial metaphysis 6 hr after ethanol was given, with the peak values occurring at a dose of 1.2 g/kg (0.4 ml). Similar increases in mRNA levels for matrix proteins were noted in lumbar vertebrae after ethanol treatment. The changes were specific for bone; ethanol had no effect on mRNA levels for matrix proteins in the uterus or liver, although the mRNA concentrations tended to be reduced in uterus. Message levels for several cytokines implicated in the regulation of bone turnover were also assayed; mRNA levels for transforming growth factor-beta1, transforming growth factor-beta2, interferon-gamma, and interleukin-6 were unchanged at doses ranging from 0.14 to 1.7 g/kg. At the highest dose of ethanol, the mRNA level for tumor necrosis factor-alpha was elevated while the level for insulin-like growth factor-1 was reduced. The time course effects of ethanol (0.4 ml dose) were determined in a separate experiment. Ethanol resulted in a transient increase in mRNA levels for the three bone matrix proteins assayed. However, matrix protein synthesis, as determined by incorporation of 3H-proline into the proximal tibial metaphysis, was not changed after 6 hr. The changes in mRNA levels for the matrix proteins were preceded by brief, transient decreases in mRNA levels for interleukin-1beta, interferon-gamma, and migration inhibitory factor, and followed by a more prolonged decrease in the mRNA level for insulin-like growth factor-1. A subsequent study was performed to determine the effects of repetitive daily treatment with ethanol on rat bone. After 7 days, there were highly significant decreases in the mRNA level for type 1 collagen, as well as decreased bone formation. These results suggest that ethanol may alter bone metabolism by disturbing signal transduction pathways that regulate the expression of genes for bone matrix proteins, skeletal growth factors, and cytokines.

Animals↗
PubMed1997

Tracer coupling pattern of amacrine and ganglion cells in the rabbit retina.

We examined the tracer coupling pattern of more than 15 morphological types of amacrine and ganglion cells in the rabbit retina. Individual cells were injected intracellularly with the biotinylated tracer Neurobiotin, which was then allowed to diffuse across gap junctions to label neighboring neurons. We found that homologous and/or heterologous tracer coupling was common for most proximal neurons. In fact, the starburst amacrine cell was the only amacrine cell type that showed no evidence of coupling. The remaining types of amacrine cell were coupled exclusively to other amacrines, either homologously or, more often, through a combination of homologous and heterologous junctions. In only one case did we visualize labeled ganglion cells following injection of Neurobiotin into an amacrine cell. In contrast, injection of Neurobiotin into ganglion cells almost always resulted in the labeling of amacrine cells. Taken together, these results suggest a directionality to the movement of tracer across gap junctions connecting amacrine and ganglion cells. We found that the coupling pattern for a given morphological type of cell was generally stereotypic and consistent across retinas. The notable exceptions to this finding were alpha ganglion cells and cells with morphology corresponding to that of on-off direction selective ganglion cells. In both cases, individual cells showed either extensive coupling to both amacrine and ganglion cells or no coupling at all. A notable finding was that, in every case, the neighboring cells within a tracer-coupled array were always within one gap junction of the injected neuron. Furthermore, in many cases, the array formed by the somata of tracer-coupled cells was almost perfectly coincident with the dendritic arbor of the injected cell. Thus, our results indicate that whereas coupling is extensive within the proximal retina, individual cells partake in coupled networks that are stereotypic and highly circumscribed.

Animals↗
PubMed1997

An overview of the issues: physiological effects of bed rest and restricted physical activity.

Reduction of exercise capacity with confinement to bed rest is well recognized. Underlying physiological mechanisms include dramatic reductions in maximal stroke volume, cardiac output, and oxygen uptake. However, bed rest by itself does not appear to contribute to cardiac dysfunction. Increased muscle fatigue is associated with reduced muscle blood flow, red cell volume, capillarization and oxidative enzymes. Loss of muscle mass and bone density may be reflected by reduced muscle strength and higher risk for injury to bones and joints. The resultant deconditioning caused by bed rest can be independent of the primary disease and physically debilitating in patients who attempt to reambulate to normal active living and working. A challenge to clinicians and health care specialists has been the identification of appropriate and effective methods to restore physical capacity of patients during or after restricted physical activity associated with prolonged bed rest. The examination of physiological responses to bed rest deconditioning and exercise training in healthy subjects has provided significant information to develop effective rehabilitation treatments. The successful application of acute exercise to enhance orthostatic stability, daily endurance exercise to maintain aerobic capacity, or specific resistance exercises to maintain musculoskeletal integrity rather than the use of surgical, pharmacological, and other medical treatments for clinical conditions has been enhanced by investigation and understanding of underlying mechanisms that distinguish physical deconditioning from the disease. This symposium presents an overview of cardiovascular and musculoskeletal deconditioning associated with reduced physical work capacity following prolonged bed rest and exercise training regimens that have proven successful in ameliorating or reversing these adverse effects.

Bed Rest↗
PubMed1997

Changes in musculoskeletal structure and function with prolonged bed rest.

Prolonged bed rest produces profound changes in muscle and bone, particularly of the lower limb. This review first addresses the various models used by researchers to study disuse-induced changes in muscle and bone as observed during prolonged bed rest in humans. Dramatic change in muscle mass occurs within 4-6 wk of bed rest, accompanied by decreases of 6 to 40% in muscle strength. Immobilization studies in humans suggest that most of this lost muscle mass and strength can be regained with appropriate resistance training within several weeks after a period of disuse. Significant decrements in bone mineral density of the lumbar spine, femoral neck, and calcaneus observed in able-bodied men after bed rest are not fully reversed after 6 months of normal weightbearing activity. Importantly, the lost bone mass is not regained for some weeks or months after muscle mass and strength have returned to normal, further contributing to the risk of fracture. Those who enter a period of bed rest with subnormal muscle and bone mass, especially the elderly, are likely to incur additional risk of injury upon reambulation. Practical implications for exercise professionals working with individuals confined to bed rest are discussed.

Animals↗
PubMed1997

Effects of vigorous exercise training and beta-agonist administration on bone response to hindlimb suspension.

The effectiveness of dobutamine (Dob) in preventing bone loss during 14 days of hindlimb suspension (Sus) was tested in exercise-trained (Ex; n = 25) and sedentary (Sed; n = 22) rats (age 155 days). One-half of each group was given Dob (2 mg . kg-1 . day-1) or saline (Sal). Histomorphometric measurements at midfemur revealed a 17% smaller cortical bone area (CBA) and a 32% lower periosteal mineral apposition rate (MAR) in suspended vs. nonsuspended Sed/Sal rats. Dob abolished this decline in CBA in Sed/Sus rats, probably via an attenuation of the decrease in periosteal MAR; similar but nonsignificant effects on cross-sectional moment of inertia were observed. Nonsuspended Ex rats had no change in bone CBA when CBA is indexed to body weight. Sus appeared to uncouple the relationship between soleus weight and CBA. Dob attenuated the 43% decline in soleus weight after Sus in Ex but not in Sed rats. In summary, vigorous Ex before Sus does not affect loss of bone mass due to unloading; Dob effectively maintains CBA in Sed rats subjected to suspension.

Adrenergic beta-Agonists↗
PubMed1996

Bone mass and endocrine adaptations to training in spinal cord injured individuals.

To investigate whether exercise training can produce increases in bone mass in spinal cord-injured (SCI) individuals with established disuse osteopenia, nine subjects (age 28.2 years, time since injury 6.0 years, level of injury C5-T7) were recruited for a 9-month training program using functional electrical stimulation cycle ergometry (FES-CE), which produces active muscle contractions in the paralyzed limb. After training, bone mineral density (BMD, by X-ray absorptiometry) increased by 0.047 +/- 0.010 g/cm2 at the lumbar spine; changes in BMD at the femoral neck, distal femur, and proximal tibia were not significant for the group as a whole. In a subset of subjects training at > or = 18 W for at least 3 months (n = 4), BMD increased by 0.095 +/- 0.026 g/cm2 (+18%) at the distal femur. By 6 months of training, a 78% increase in serum osteocalcin was observed, indicating an increase in bone turnover. Urinary calcium and hydroxyproline, indicators of resorptive activity, did not change over the same period. Serum PTH increased 75% over baseline values (from 2.98 +/- 0.15 to 5.22 +/- 0.62 pmol/L) after 6 months' training, with several individual values in hyperparathyroid range; PTH declined toward baseline values by 9 months. These data establish the feasibility of stimulating site-specific increases in bone mass in severely osteopenic bone with muscle contractions independent of weight-bearing for those subjects able to achieve a threshold power output of 18 W with FES-CE. Calcium supplementation from the outset of training in osteopenic individuals may be advisable to prevent training-induced increases in PTH.

Adult↗