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NASA NTRS1992

Effects of COMT inhibitors on striatal dopamine metabolism: A microdialysis study

In vivo microdialysis was used to examine the effect of two new catechol-O-methyltransferase (COMT) inhibitors, Ro 40-7592 and OR-611, on extracellular levels of dopamine, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in rat striatum. The interactions of the COMT inhibitors with nomifensine, clorgyline, and deprenyl were also studied. Ro 40-7592 (3-30 mg/kg. i.p.) decreased dose-dependently the efflux of HVA, increased that of DOPAC, and tended to increase that of dopamine. Higher doses of OR-611 (30-100 mg/kg, i.p.) also decreased the dialysate level of HVA, increased that of DOPAC, and tended to increase that of dopamine. Ro 40-7592 was about ten-fold as potent as OR-611. Neither of the COMT inhibitors changed dialysate levels of 6-HIAA. An OR-611 dose of 10 mg/kg i.p. had no significant effect, in contrast to Ro 40-7592, on any of the parameters studied; this dose was thus used to differentiate between the effects of central and peripheral COMT inhibition. Both nomifensine (15 mg/kg, i.p.) and clorgyline (4 mg/kg, i.p.) alone elevated extracellular dopamine levels, and lowered those of DOPAC and HVA, though there were quantitative and temporal differences between the drugs. L-deprenyl (1 mg/kg, i.p.) alone had no significant effect on any of the compounds measured. Ro 40-7592 (10 mg/kg, i.p.) potentiated the effect of nomifensine on dopamine efflux, and it tended to increase clorgyline-induced dopamine efflux. DOPAC levels in dialysates were significantly increased by combinations of Ro 40-7592 and nomifensine or clorgyline, whereas HVA remained about as low as they were after Ro 40-7592 alone. Ro 40-7592 had no significant interactions with L-deprenyl. OR-611 (10 mg/kg, i.p.) did not modify the effects on dopamine metabolism of nomifensine, clorgyline, or L-deprenyl. These data show that Ro 40-7592 is a potent centrally active COMT inhibitor, whereas OR-611 is principally a peripherally active inhibitor. Use of drugs which inhibit brain COMT can considerably modify dopamine metabolism. COMT inhibitors may be of clinical significance in treating Parkinson's disease.

Kaakkola, S.↗

NASA NTRS1947

Wind-tunnel investigation of the effect of power and flaps on the static lateral characteristics of a single-engine low-wing airplane model

Tests were made in the Langley 7- by 10-foot tunnel to determine the lateral-stability characteristics with and without power of a model of a typical low-wing single-engine airplane with flaps neutral, with a full-span single slotted flap, and with a full-span double slotted flap. Power decreased the dihedral effect regardless of flap condition, and the double-slotted flap configuration showed the most marked decrease. The usual effect of power in increasing the directional stability was also shown. Deflection of the single slotted flap produced negative dihedral effect, but increased the directional stability. The effects of deflecting the double slotted flap were erratic and marked changes in both effective dihedral and directional stability occurred. The addition of the tail surfaces always contributed directional stability and generally produced positive dihedral effect.

Tamburello, Vito↗

NASA NTRS1946

Wind-tunnel Investigation of End-plate Effects of Horizontal Tails on a Vertical Tail Compared with Available Theory

A vertical-tail model with stub fuselage was tested in combination with various simulated horizontal tails to determine the effect of horizontal-tail span and location on the aerodynamic characteristics of the vertical tail. Available theoretical data on end-plate effects were collected and presented in the form most suitable for design purposes. Reasonable agreement was obtained between the measured and theoretical end-plate effects of horizontal tails on vertical tails, and the data indicated that the end-plate effect was determined more by the location of the horizontal tail than by the span of the horizontal tail. The horizontal tail gave most end-plate effect when located near either tip of the vertical tail and, when located near the base of the vertical tail, the end-plate effect was increased by moving the horizontal tail rearward.

TAIL SURFACES - HINGE MOMENTS↗

NASA NTRS1925

Relation of "Lilienthal effect" to dynamic soaring flight

In this article, the phenomena of the upward component in the case of flat surfaces will be referred to as the "Lilienthal effect." The Lilienthal effect will be distinguished from the Knoller-Betz effect which is explained by means of vertical wind oscillations, at the basis of which, however, there lie air motions which the Lilienthal effect could not produce. It will be shown that the same cause, which can produce the Lilienthal effect on flat airfoils, considerably strengthens the thrust due to the Knoller-Betz effect.

Fick, Roderich↗

NASA NTRS1994

Effects of fiber, matrix, and interphase on carbon fiber composite compression strength

The major goal of this project was to obtain basic information on compression failure properties of carbon fiber composites. To do this, we investigated fiber effects, matrix effects, and fiber/matrix interface effects. Using each of nine fiber types, we prepared embedded single-fiber specimens, single-ply specimens, and full laminates. From the single-fiber specimens, in addition to the standard fragmentation test analysis, we were able to use the low crack density data to provide information about the distribution of fiber flaws. The single-ply specimens provided evidence of a correlation between the size of kink band zones and the quality of the interface. Results of the laminate compression experiments mostly agreed with the results from single-ply experiments, although the ultimate compression strengths of laminates were higher. Generally, these experiments showed a strong effect of interfacial properties. Matrix effects were examined using laminates subjected to precracking under mixed-mode loading conditions. A large effect of precracking conditions on the mode 1 toughness of the laminates was found. In order to control the properties of the fiber/matrix interface, we prepared composites of carbon fiber and polycarbonate and subjected these to annealing. The changes in interfacial properties directly correlated with changes in compression strength.

Nairn, John A.↗

NASA NTRS1995

Numerical Study of Contaminant Effects on Combustion of Hydrogen, Ethane, and Methane in Air

A numerical study was performed to assess the effects of vitiated air on the chemical kinetics of hydrogen, ethane, and methane combustion with air. A series of calculations in static reacting systems was performed, where the initial temperature was specified and reactions occurred at constant pressure. Three different types of test flow contaminants were considered: NP, H2O, and a combustion of H2O and CO2. These contaminants are present in the test flows of facilities used for hypersonic propulsion testing. The results were computed using a detailed reaction mechanism and are presented in terms of ignition and reaction times. Calculations were made for a wide range of contaminant concentrations, temperatures and pressures. The results indicate a pronounced kinetic effect over a range of temperatures, especially with NO contamination and, to a lesser degree, with H2O contamination. In all cases studied, CO2 remained kinetically inert, but had a thermodynamic effect on results by acting as a third body. The largest effect is observed with combustion using hydrogen fuel, less effect is seen with combustion of ethane, and little effect of contaminants is shown with methane combustion.

Lai, H. T.↗

NASA NTRS1995

From LDEF to a national Space Environment and Effects (SEE) program: A natural progression

As the LDEF program draws to a close, it leaves in place the fundamental building blocks for a Space Environment and Effects (SEE) program. Results from LDEF data analyses and investigations now form a substantial core of knowledge on the long term effects of the space environment on materials, system and structures. In addition, these investigations form the basic structure of a critically-needed SEE archive and database system. An agency-wide effort is required to capture all elements of a SEE program to provide a more comprehensive and focused approach to understanding the space environment, determining the best techniques for both flight and ground-based experimentation, updating the models which predict both the environments and those effects on subsystems and spacecraft, and, finally, ensuring that this multitudinous information is properly maintained, and inserted into spacecraft design programs. Many parts and pieces of a SEE program already exist at various locations to fulfill specific needs. The primary purpose of this program, under the direction of the Office of Advanced Concepts and Technology (OACT) in NASA Headquarters, is to take advantage of these parts; apply synergisms where possible; identify and when possible fill-in gaps; coordinate and advocate a comprehensive SEE program. The SEE program must coordinate and support the efforts of well-established technical communities wherein the bulk of the work will continue to be done. The SEE program will consist of a NASA-led SEE Steering Committee, consisting of government and industry users, with the responsibility for coordination between technology developers and NASA customers; and Technical Working Groups with primary responsibility for program technical content in response to user needs. The Technical Working Groups are as follows: Materials and Processes; Plasma and Fields; Ionizing Radiation; Meteoroids and Orbital Debris; Neutral External Contamination; Thermosphere, Thermal, and Solar Conditions; Electromagnetic Effects; Integrated Assessments and Databases. Specific technology development tasks will be solicited through a NASA Research Announcement to be released in May of 1994. The areas in which tasks are solicited include: (1) engineering environment definitions, (2) environments and effects design guidelines, (3) environments and effects assessment models and databases, and (4) flight/ground simulation/technology assessment data.

Bowles, David E.↗

NASA NTRS1995

Analytical investigation of the hygrothermal effects and parametric study of the Edge Crack Torsion (ECT) mode 3 test lay-ups

A shear deformation theory including residual thermal and moisture effects is developed for the analysis of either symmetric or unsymmetric laminates with mid-plane edge delamination under torsion loading. The theory is based on an assumed displacement field which includes shear deformation. The governing equations and boundary conditions are obtained from the principle of virtual work. The analysis of the (90/(+/- 45)(n)/(-/+ 45)(n)/90)(s) ECT mode 3 test lay-up indicates that there are no hygrothermal effects on the mode 3 strain energy release rate because the laminate, and both sublaminates above and below the delamination, are symmetric lay-ups. A further parametric study reveals that some other lay-ups can have negligible hygrothermal effects even when the sublaminates above and below the delamination are not symmetric about their own mid-planes. However, these lay-ups may suffer from distortion after the curing process. Another Interesting set of lay-ups investigated is a class of antisymmetric laminates with (+/-(theta/(theta -90)(2)/theta))(n) lay-ups. It is observed that when n takes on even numbers (2 and 4), both hygrothermal and mode 1 effects can be neglected. From this point of view, these lay-ups provide a way to determine the mode 3 toughness between two dissimilar layers. However, when n takes on odd numbers (1 and 3), both hygrothermal and mode 1 effects may be strong in these lay-ups. In particular, when theta equals 45 deg, the lay-ups are free from both hygrothermal and mode 1 effects irrespective of n.

Li, Jian↗

NASA NTRS1995

Numerical study of contaminant effects on combustion of hydrogen, ethane, and methane in air

A numerical study was performed to assess the effects of vitiated air on the chemical kinetics of hydrogen, ethane, and methane combustion with air. A series of calculations in static reacting systems was performed, where the initial temperature was specified and reactions occurred at constant pressure. Three different types of test flow contaminants were considered: NO, H2O, and a combination of H2O and CO2. These contaminants are present in the test flows of facilities used for hypersonic propulsion testing. The results were computed using a detailed reaction mechanism and are presented in terms of ignition and reaction times. Calculations were made for a wide range of contaminant concentrations, temperatures and pressures. The results indicate a pronounced kinetic effect over a range of temperatures, especially with NO contamination and, to a lesser degree, with H2O contamination. In all cases studied, CO2 remained kinetically inert, but had a thermodynamically effect on results by acting as a third body. The largest effect is observed with combustion using hydrogen fuel, less effect is seen with combustion of ethane, and little effect of contaminants is shown with methane combustion.

Lai, H. T.↗

NASA NTRS1996

Ice Detector and Deicing Fluid Effectiveness Monitoring System

An ice detector and deicing fluid effectiveness monitoring system for an aircraft is disclosed. The ice detection portion is particularly suited for use in flight to notify the flight crew of an accumulation of ice on an aircraft lifting and control surfaces, or helicopter rotors, whereas the deicing fluid effectiveness monitoring portion is particularly suited for use on the ground to notify the flight crew of the possible loss of the effectiveness of the deicing fluid. The ice detection portion comprises a temperature sensor and a parallel arrangement of electrodes whose coefficient of coupling is indicative of the formation of the ice, as well as the thickness of the formed ice. The fluid effectiveness monitoring portion comprises a temperature sensor and an ionic-conduction cell array that measures the conductivity of the deicing fluid which is indicative of its concentration and, thus, its freezing point. By measuring the temperature and having knowledge of the freezing point of the deicing fluid, the fluid effectiveness monitoring portion predicts when the deicing fluid may lose its effectiveness because its freezing point may correspond to the temperature of the ambient.

Seegmiller, H. Lee B.↗

NASA NTRS1996

Marangoni Effects in the Boiling of Binary Fluid Mixtures

Results of very recent experimental studies indicate that during nucleate boiling in some binary mixture, Marangoni effects augment the gravity driven flow of liquid towards the heated surface. With gravity present, it is impossible to separate the two effects. The reduced gravity environment gives an unique opportunity to explore th role of Marangoni effects on the boiling mechanisms free of gravitational body forces that obscure the role of such effects. However, recent experimental results suggest that under reduced gravity conditions, Marangoni effects is the dominant mechanism of vapor-liquid exchange at the surface for some binary mixture. To further explore such effects, experiments have been conducted with water/2-propanol mixtures at three different concentrations under normal gravity with different orientations of the heater surface and under reduce gravity aboard the DC-9 aircraft at NASA Lewis Research Center. The system pressure was sub atmospheric (approx. 8 kP at 1g(n)) and the bulk liquid temperature varied from low subcooling to near saturation. The molar concentrations of 2-propanol tested were 0.015, 0.025, and 0.1. Boiling curves were obtained both for high gravity (approx. 2g(n)) and reduce gravity (approx. 0.01g(n)). For each concentration of 2-propanol, the critical heat flux has been determined in the flight experiments only for reduced gravity conditions. Comparison of boiling curves and CHF obtained under l-g(n) an reduced gravity indicates that boiling mechanism in this mixtures is nearly independent of gravity. The results also indicate that the Marangoni mechanism is strong enough in these mixtures to sustain the boiling under reduced gravity conditions.

Ahmed, Sayeed↗

NASA NTRS1997

Effects of Buoyancy on Laminar and Turbulent Premixed V-Flame

Turbulent combustion occurs naturally in almost all combustion systems and involves complex dynamic coupling of chemical and fluid mechanical processes. It is considered as one of the most challenging combustion research problems today. Though buoyancy has little effect on power generating systems operating under high pressures (e.g., IC engines and turbines), flames in atmospheric burners and the operation of small to medium furnaces and boilers are profoundly affected by buoyancy. Changes in burner orientation impacts on their blow-off, flash-back and extinction limits, and their range of operation, burning rate, heat transfer, and emissions. Theoretically, buoyancy is often neglected in turbulent combustion models. Yet the modeling results are routinely compared with experiments of open laboratory flames that are obviously affected by buoyancy. This inconsistency is an obstacle to reconciling experiments and theories. Consequently, a fundamental understanding of the coupling between turbulent flames and buoyancy is significant to both turbulent combustion science and applications. The overall effect of buoyancy relates to the dynamic interaction between the flame and its surrounding, i.e., the so-called elliptical problem. The overall flame shape, its flowfield, stability, and mean and local burning rates are dictated by both upstream and downstream boundary conditions. In steady propagating premixed flames, buoyancy affects the products region downstream of the flame zone. These effects are manifested upstream through the mean and fluctuating pressure fields to influence flame stretch and flame wrinkling. Intuitively, the effects buoyancy should diminish with increasing flow momentum. This is the justification for excluding buoyancy in turbulent combustion models that treats high Reynolds number flows. The objectives of our experimental research program is to elucidate flame-buoyancy coupling processes in laminar and turbulent premixed flames, and to characterize microgravity (micro g) premixed flames. The results are used to derive appropriate scaling parameters for guiding the development of theoretical models to include the effects of buoyancy. Knowledge gain from the analysis will also contribute to further understanding of the elliptical nature of premixed flames. Our current emphasis is to examine the momentum limit above which the effects of buoyancy would become insignificant. This is accomplished by comparing the flowfields and the mean properties of normal gravity flames (+g), and reversed gravity flames (-g, up-side-down flames) at different flow velocities and turbulence intensities. Microgravity (micro g) flames experiments provide the key reference data to reconcile the differences between flames in +g and -g. As flame configuration has significant impact on premixed flames characteristics we have studied axi-symmetric conical flames and plane-symmetric rod-stabilized v-flames. The two configurations produce distinct features that dictates how the flames couple with buoyancy. In a conical flame, the hot products plume completely envelopes the flame cone and shields the flame from direct interaction with the ambient air. The plume originates at the burner rim and generates a divergent flowfield. In comparison, the products region of v-flames forms between the twin flame sheets and it is convergent towards the center-plane. Interaction with ambient air is limited to the two end regions of the stabilized rod and beyond the flame sheets.

Cheng, Robert K.↗

NASA NTRS1961

Aerodynamic Characteristics of a Four-Propeller Tilt-Wing VTOL Model with Twin Vertical Tails, Including Effects of Ground Proximity

Results are presented of a wind-tunnel investigation of the aerodynamic stability, control, and performance characteristics of a model of a four-propeller tilt-wing VTOL airplane employing flaps and speed brakes through the transition speed range. The results indicate that the wing was stalled for steady level flight for all conditions of the investigation; however, the flapped configuration did produce a higher maximum lift. The effectiveness of the flap in delaying the stall in the present investigation was not as great as in some previous investigations because the flap used was smaller than that used previously. The wing stall resulted in an appreciable reduction of aileron effectiveness during the transition. Out of ground effect the low horizontal tail did not appear to be in an adverse flow field as had been expected and showed no erratic changes in effectiveness; however, in ground effect a large nose-down moment was experienced by the model. In general, the lateral aerodynamic data indicate that the configuration is directionally stable and possesses positive dihedral effect throughout the transition, and the data show no signs of erratic flow at the vertical tails.

Grunwald, Kalman J.↗

NASA NTRS1999

Effects of Microgravity on the Formation of Aerogels

This paper describes research to investigate fundamental aspects of the effects of microgravity on the formation of the microstructure of metal oxide alcogels and aerogels. We are studying the role of gravity on pore structure and gel uniformity in collaboration with Marshall Space Flight Center (MSFC) on gelling systems under microgravity conditions. While this project was just initiated in May 1998, related research performed earlier is described along with the plans and rationale for the current microgravity investigation to provide background and describe newly developing techniques that should be useful for the current gellation studies. The role of gravity in materials processing must be investigated through the study of well-mastered systems. Sol-gel processed materials are near-perfect candidates to determine the effect of gravity on the formation and growth of random clusters from hierarchies of aggregated units. The processes of hydrolysis, condensation, aggregation and gellation in the formation of alcogels are affected by gravity and therefore provide a rich system to study under microgravity conditions. Supercritical drying of the otherwise unstable wet alcogel preserves the alcogel structure produced during sol-gel processing as aerogel. Supercritically dried aerogel provides for the study of material microstructures without interference from the effects of surface tension, evaporation, and solvent flow. Aerogels are microstructured, low density open-pore solids. They have many unusual properties including: transparency, excellent thermal resistance, high surface area, very low refractive index, a dielectric constant approaching that of air, and extremely low sound velocity. Aerogels are synthesized using sol-gel processing followed by supercritical solvent extraction that leaves the original gel structure virtually intact. These studies will elucidate the effects of microgravity on the homogeneity of the microstructure and porosity of aerogel. The presence of poorly controlled microporosity in aerogel leads to material non-uniformity that gives rise to increased light scattering. Investigation of the effect of gravity driven solute flows within microclusters and their effect on condensation and agglomeration reactions will enable us to improve the preparation and properties of aerogel. Increased clarity of images viewed through aerogel and decreased scattering from the pores of aerogel will significantly improve the prospects for large-scale adoption of aerogel in such applications as transparent insulating windows, high performance thermal insulation, and Cherenkov detectors.

Hunt, A. J.↗

NASA NTRS1997

Compensation for Spherical Geometric and Absorption Effects on Lower Thermospheric Emission Intensities Derived from High Earth Orbit Images

Remote sensing of the atmosphere from high earth orbit is very attractive due to the large field of view obtained and a true global perspective. This viewpoint is complicated by earth curvature effects so that slant path enhancement and absorption effects, small from low earth orbit, become dominant even at small nadir view angles. The effect is further complicated by the large range of local times and solar zenith angles in a single image leading to a modulation of the image intensity by a significant portion of the diurnal height variation of the absorbing layer. The latter effect is significant in particular for mesospheric, stratospheric and auroral emissions due to their depth in the atmosphere. As a particular case, the emissions from atomic oxygen (130.4 and 135.6 nm) and molecular nitrogen (two LBH bands, LBHS from 140 to 160 nm and LBHL from 160 to 180 nm) as viewed from the Ultraviolet Imager (UVI) are examined. The LBH emissions are of particular interest since LBHS has significant 02 absorption while LBHL does not, In the case of auroral emissions this differential absorption, well examined in the nadir, gives information about the height of the emission and therefore the energy of the precipitating particles. Using simulations of the viewing geometry and images from the UVI we examine these effects and obtain correction factors to adjust to the nadir case with a significant improvement of the derived characteristic energy. There is a surprisingly large effect on the images from the 02 diurnal layer height changes. An empirical compensation to the nadir case is explored based on the local nadir and local zenith angles for each portion of the image. These compensations are demonstrated as applied to the above emissions in both auroral and dayglow images and compared to models. The extension of these findings to other instruments, emissions and spectral regions is examined.

Swift, W.↗

NASA NTRS1996

An Electrothermodynamic Model with Distributed Properties for Effective Permittivities of Sea Ice

This paper presents a model to calculate the temperature dependence of effective permittivities for sea ice, a heterogeneous medium containing multiphase scatterers. With the strong permittivity fluctuation approach the model accounts for the electrodynamic scattering effect together with the quasi-static characteristics of multiple species and subspecies of inhomogeneities with distributed orientations, sizes, and shapes. Because of a preferential direction in the orientation distribution, the medium is effectively anisotropic. The size distribution is described with a probability density function in terms of normalized volumetric sizes. Scatterer shapes are nonuniform and have a general ellipsoidal form characterized by arbitrary axial ratios of correlation lengths which are related to physical geometries of the scatterers. In this formulation, sea ice consisting of solid ice, liquid brine, and gaseous inclusions is modeled to derive effective permittivities with thermodynamic phase redistribution and structural metamorphism. Theoretical results are in good agreement with experimental data at the C band frequency of 4.8 GHz for saline ice undergoing warming and cooling cycles. A competitive effect between the increase of liquid brine and the shape rounding of ellipsoidal scatterers at increasing temperatures explains the trend observed in measured data. Sensitivities of effective permittivities to structural and physical parameters characterizing sea ice are also studied.

Nghiem, S. V.↗

NASA NTRS1998

NASA's Space Environments and Effects (SEE) Program: The Pursuit of Tomorrow's Space Technology

A hazard to all spacecraft orbiting the earth and exploring the unknown in deep space is the existence of a harsh and ever changing environment with its subsequent effects. Some of these environmental hazards, such as plasma, extreme thermal excursions, meteoroids, and ionizing radiation result from natural sources, whereas others, such as orbital debris and neutral contamination are induced by the presence of spacecraft themselves. The subsequent effects can provide damaging or even disabling effects on spacecraft, its materials, and its instruments. In partnership with industry, academia, and other government agencies, National Aeronautics & Space Administration's (NASA's) Space Environments & Effects (SEE) Program defines the space environments and advocates technology development to accommodate or mitigate these harmful environments on the spacecraft. This program provides a very comprehensive and focused approach to understanding the space environment, to define the best techniques for both flight and ground-based experimentation, to update the models which predict both the environments and the environmental effects on spacecraft, and finally to ensure that this information is properly maintained and inserted into spacecraft design programs. This paper will provide an overview of the Program's purpose, goals, database management and technical activities. In particular, the SEE Program has been very active in developing improved ionizing radiation models and developing related flight experiments which should aid in determining the effect of the radiation environment on modern electronics.

Pearson, Steven D.↗

NASA NTRS1999

The Effect of Skeletal Unloading on Bone Formation: Role of IGF-I

The best documented change in bone during space flight is the near cessation of bone formation. Space flight leads to a decrease in osteoblast number and activity, likely the result of altered differentiation of osteoblast precursors. The net result of these space flight induced changes is weaker bone. To understand the mechanism for these changes poses a challenge. Space flight studies must overcome enormous technical problems, and are necessarily limited in size and frequency. Therefore, ground based models have been developed to evaluate the effects of skeletal unloading. The hindlimb elevation (tail suspension) model simulates space flight better than other models because it reproduces the fluid shifts seen in space travel, is reversible, and is well tolerated by the animals with minimal evidence of stress as indicated by continued weight gain and normal levels and circadian rhythms of corticosterone. This is the model we have used for our experiments. Skeletal unloading by the hindlimb elevation method simulates a number of features of space flight in that bone formation, mineralization, and maturation are inhibited, osteoblast number is decreased, serum and skeletal osteocalcin levels fall, the ash content of bone decreases, and bone strength diminishes. We and others have shown that when osteoblasts or osteoprogenitor cells from the bones of the unloaded limbs are cultured in vitro they proliferate and differentiate more slowly, suggesting that skeletal unloading causes a persistent change in cell function which can be assessed in vitro. In contrast to the unweighted bones of the hindlimbs, no significant change in bone mass or bone formation is observed in the humeri, mandible, and cervical vertebrae during hindlimb elevation. The lack of effect of hindlimb elevation on bones like the humeri, mandible, and cervical vertebrae which are not unloaded by this procedure suggests that local factors rather than systemic effects dominate the response of bone to skeletal unloading. We have focussed on the role of IGF- 1 as the local factor mediating the effects of skeletal unloading on bone formation. IGF-I is produced by bone cells and chondrocytes; these cells have receptors for IGF-I, and respond to IGF-I with an increase in proliferation and function (e.g. collagen, and glycosaminoglycan production, respectively). IGF-I production by bone is under hormonal control, principally by GH and PTH, and IGF-I is thought to mediate some if not all of the effects of GH and PTH on bone growth. Thus, systemic changes in hormones such as GH and PTH may still have effects which vary from bone to bone depending on the loading history.

Bikle, D. D.↗