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PubMed2006

The stumbling block in lung repair of emphysema: elastic fiber assembly.

The mechanical properties of the lung are largely determined by the connective tissue networks laid down during development. The macromolecules most important for lung mechanics and structural integrity are collagen, elastin, and proteoglycans. Members of the fibrillar collagen gene family provide the structural framework of the various lung compartments and elastic fibers provide elastic recoil. Elastin is also an important architectural component that influences lung development, predominantly during the alveolar stage. Previous studies have conclusively shown that elastin degradation is a key step in the pathogenesis of chronic obstructive pulmonary disease. Exacerbating the disease process is the inability of lung cells to repair damaged elastic fibers, which leads to permanently compromised lung function and ongoing degenerative disease. Elastic fibers are among the most difficult matrix structures to repair because of their size, molecular complexity, and the requirement for numerous helper proteins to facilitate fiber assembly. Recent studies of elastin assembly combined with new insight into the functional role of elastic fiber proteins obtained from gene inactivation studies and linkage of human disease to elastin mutations provide new insight into the molecular and cellular complexities of elastin homeostasis.

Animals↗
PubMed1998

Degradation and repair of elastic fibers in rat lung interstitial fibroblast cultures.

BACKGROUND: Evidence from in vitro and in vivo studies indicates that damaged elastic fibers can be repaired. METHODS: Lipid interstitial pulmonary fibroblasts were cultured for 6 weeks. Cultures were then exposed to 25 microg of porcine pancreatic elastase and fixed in pairs (control, elastase-treated) immediately after exposure and at 1, 2, 3, 4, 7, 10, 14, and 22 days for ultrastructural examination. Elastin was also analyzed biochemically for resistance to hot alkali, an indicator of repair. Steady-state levels of tropoelastin and lysyl oxidase mRNA at 2, 4, and 7 days after elastase treatment were determined by Northern blot analysis. RESULTS: Immediately after exposure to elastase, damaged elastic fibers exhibited a frayed, porous appearance and a granular texture. Through day 4, fibers showed no evidence of repair. By day 7, the granular texture of damaged fibers was no longer evident and a gradual filling-in of porous areas appeared to be taking place. By 22 days, elastic fibers were indistinguishable from elastic fibers in control cultures. The ultrastructural changes were paralleled by changes in hot alkali resistance. Through day 4, there was no change in the level of hot alkali resistant elastin. Between day 4 and day 7, resistance to hot alkali increased sharply and continued to increase at a slower rate, reaching 84% of the control level by day 22. Steady-state levels of tropoelastin and lysyl oxidase mRNA showed no increase over control levels at 2, 4, and 7 days after elastase treatment. CONCLUSIONS: Elastic fibers synthesized by lipid interstitial pulmonary fibroblasts in culture were repaired after damage by elastase. This type of repair may have relevance to the prevention of pathological conditions, such as emphysema.

Animals↗
PubMed1997

Altered mechanical properties in aortic elastic tissue using glutaraldehyde/solvent solutions of various dielectric constant.

The extent to which elastic tissue can be crosslinked in aldehydes and the mechanism of such action is unresolved in the literature. We have used glutaraldehyde/solvent solutions of decreasing dielectric constant (phosphate buffer, methanol, 95% ethanol, n-propanol, n-butanol) to alter the mechanical properties of aortic elastic tissue obtained from autoclaved and CNBr-purified bovine aortae. Treated and untreated hoop samples were examined for stress-strain and stress relaxation behavior and for residual stress using opening angle experiments as per Fung. The extent of exogenous crosslinking was analyzed through amino acid analysis. Mechanical properties of autoclaved elastic tissue varied with dielectric constant in glutaraldehyde/solvent treatments; however, solvent treatment alone produced no effect. Extensibility decreased with decreasing dielectric constant while tensile modulus changed over a range from -2.4% (-0.86 kPa) for glutaraldehyde/buffer to +35.3% (+14.3 kPa) for glutaraldehyde/n-propanol (untreated-treated). Residual stress experiments similarly showed a systematic decrease in opening angle with decreasing dielectric constant. Differences ranged from 10.5 degrees for glutaraldehyde/buffer to 22.2 degrees for glutaraldehyde/n-butanol. Interestingly, purification of aortae with CNBr reduced the effects of glutaraldehyde/n-butanol treatment. We hypothesize that CNBr differentially degraded the elastin-associated microfibrillar proteins in aortic elastic tissue, thus producing the observed differences in mechanical behavior. The observed phenomena in this study may be attributed to the composite structure of elastic tissue: elastin and microfibrillar protein. During treatment, conformational changes in elastin facilitated by polar/nonpolar interactions occurred which then were "locked" in by glutaraldehyde crosslinking of the microfibrillar proteins. By this mechanism the increases in both stiffness and time-dependent behavior observed after treatment may be explained.

Amino Acids↗
PubMed2000

Elastic properties and masticatory bone stress in the macaque mandible.

One important limitation of mechanical analyses with strain gages is the difficulty in directly estimating patterns of stress or loading in skeletal elements from strain measurements. Because of the inherent anisotropy in cortical bone, orientation of principal strains and stresses do not necessarily coincide, and it has been demonstrated theoretically that such differences may be as great as 45 degrees (Cowin and Hart, 1990). Likewise, relative proportions of stress and strain magnitudes may differ. This investigation measured the elastic properties of a region of cortical bone on both the buccal and lingual surfaces of the lower border of the macaque mandible. The elastic property data was then combined with macaque mandibular strain data from published and a new in vivo strain gage experiment to determine directions and magnitudes of maximum and minimum principal stresses. The goal was to compare the stresses and strains and assess the differences in orientation and relative magnitude between them. The main question was whether these differences might lead to different interpretations of mandibular function. Elastic and shear moduli, and Poisson's ratios were measured using an ultrasonic technique from buccal and lingual cortical surfaces in 12 macaque mandibles. Mandibular strain gage data were taken from a published set of experiments (Hylander, 1979), and from a new experiment in which rosette strain gauges were fixed to the buccal and lingual cortices of the mandibular corpus of an adult female Macaca fascicularis, after which bone strain was recorded during mastication. Averaged elastic properties were combined with strain data to calculate an estimate of stresses in the mandibular corpus. The elastic properties were similar to those of the human mandibular cortex. Near its lower border, the macaque mandible was most stiff in a longitudinal direction, less stiff in an inferosuperior direction, and least stiff in a direction normal to the bone's surface. The lingual aspect of the mandible was slightly stiffer than the buccal aspect. Magnitudes of stresses calculated from average strains ranged from a compressive stress of -16.00 GPa to a tensile stress of 8.84 GPa. The orientation of the principal stresses depended on whether the strain gage site was on the working or balancing side. On the balancing side of the mandibles, maximum principal stresses were oriented nearly perpendicular to the lower border of the mandible. On the working side of the mandibles, the orientation of the maximum principal stresses was more variable than on the balancing side, indicating a larger range of possible mechanisms of loading. Near the lower border of the mandible, differences between the orientation of stresses and strains were 12 degrees or less. Compared to ratios between maximum and minimum strains, ratios between maximum and minimum stresses were more divergent from a ratio of 1.0. Results did not provide any major reinterpretations of mandibular function in macaques, but rather confirmed and extended existing work. The differences between stresses and strains on the balancing side of the mandible generally supported the view that during the power stroke the mandible was bent and slightly twisted both during mastication and transducer biting. The calculated stresses served to de-emphasize the relative importance of torsion. On the working side, the greater range of variability in the stress analysis compared to the strain analysis suggested that a more detailed examination of loadings and stress patterns in each individual experiment would be useful to interpret the results. Torsion was evident on the working side; but in a number of experiments, further information was needed to interpret other superimposed regional loading patterns, which may have included parasagittal bending and reverse parasagittal bending.

Animals↗
PubMed1977

Elastic tissue in the limiting membrane of the human seminiferous tubule.

The structure and distribution of elastic tissue were studied in the limiting membrane of the seminiferous tubule from normal human testis. The elastic and elastic-related fibers (oxytalan and elaunin) were recognized by their tinctorial and ultrastructural characteristics. The connective structures of the limiting membrane, including the fibrotubules and the amorphous material of the elastic system, were studied after tannic acid-glutaraldehyde fixation. Fibrotubules (oxytalan fibers) were observed in almost all intercellular spaces of the limiting membrane, closely related to the contractile cells; the elaunin fibers (patches of amorphous material surrounded by bundles of fibrotubules) were evident in the outermost layers. The function of this system of elastic tissue and myoid cells is discussed, considering the permeability membrane and the role of the myoid cells in the elastogenesis and contractility of the seminiferous tubule.

Elastic Tissue↗
PubMed2006

Elastic properties of external cortical bone in the craniofacial skeleton of the rhesus monkey.

Knowledge of elastic properties and of their variation in the cortical bone of the craniofacial skeleton is indispensable for creating accurate finite-element models to explore the biomechanics and adaptation of the skull in primates. In this study, we measured elastic properties of the external cortex of the rhesus monkey craniofacial skeleton, using an ultrasonic technique. Twenty-eight cylindrical cortical specimens were removed from each of six craniofacial skeletons of adult Macaca mulatta. Thickness, density, and a set of longitudinal and transverse ultrasonic velocities were measured on each specimen to allow calculation of the elastic properties in three dimensions, according to equations derived from Newton's second law and Hooke's law. The axes of maximum stiffness were determined by fitting longitudinal velocities measured along the perimeter of each cortical specimen to a sinusoidal function. Results showed significant differences in elastic properties between different functional areas of the rhesus cranium, and that many sites have a consistent orientation of maximum stiffness among specimens. Overall, the cortical bones of the rhesus monkey skull can be modeled as orthotropic in many regions, and as transversely isotropic in some regions, e.g., the supraorbital region. There are differences from human crania, suggesting that structural differences in skeletal form relate to differences in cortical material properties across species. These differences also suggest that we require more comparative data on elastic properties in primate craniofacial skeletons to explore effectively the functional significance of these differences, especially when these differences are elucidated through modeling approaches, such as finite-element modeling.

Animals↗
PubMed2002

Distribution of the elastic fiber and associated proteins in flexor tendon reflects function.

The elastic fiber is known to be an important component of skin, lung, and vasculature. Much less is known about the distribution of elastin and elastic fiber-related proteins in connective tissues, yet genetic defects of elastic fiber constituents can lead to deficiencies in these tissues. For the first time, we determine the distribution of elastin, fibrillins 1 and 2, and microfibril-associated glycoproteins (MAGPs) 1 and 2 in the flexor digitorum profundus (FDP) tendon. Three functionally distinct regions of the FDP tendon, the fibrocartilagenous (FC) region, avascular/tensional (AV/T) region, and insertion region, were evaluated by immunohistochemical methods for these five proteins. Biochemical analysis of desmosine content, an elastin-specific cross-link, demonstrated the presence of elastin in each region, and this was verified histochemically. The fibrillins were found with elastin and also pericellularly with internal fibroblasts where elastin was not detected. Although there was overlapping distribution, fibrillin 2 was more prominent in the interior of the tendon while fibrillin 1 was prominent in outer cell layers that contained elastic fibers. Both MAGP-1 and -2 were found throughout the tendon, although the greatest abundance was near the tendon insertion to bone. Surprisingly, MAGP-1 demonstrated a filamentous appearance within the fibrocartilage that did not correspond to the fibrillin 1 or 2 or MAGP-2 staining pattern. Lastly, we have shown that a vincular membrane located along the dorsal surface of the tendon near the insertion has a very high elastin content and a unique interface with the tendon that consists of an elastic anchor within the tendon body.

Animals↗
PubMed1987

Segmental variations in the elastic fiber content of the lateral costotransverse ligaments in the vervet monkey (Cercopithecus pygerythrus aethiops).

The segmental and zonal variations in the quantitative relationships between elastic and collagen fibers within the lateral costotransverse ligaments have been investigated in the vervet monkey. The lateral costotransverse ligaments of the caudal segments have a largely elastic structure in contrast to those of the cranial segments, which are characteristically collagenous. In the transitional zone extending from the 4th through to the 6th costotransverse joints, the lateral costotransverse ligaments show a zonal differentiation into a superficial collagenous portion and a deep elastic portion. It is noted that the craniocaudal structural differentiation in the lateral costotransverse ligaments corresponds with similar changes in the vertebral ligaments in that the ligamenta flava gradually extend into the interspinous spaces from the 1st thoracic vertebra (T1) so that at T5 the ligaments occupy 50% of the interspinous space and at T7 the elastic fibers almost completely replace the interspinous ligament. Functionally, however, the regional differences in the elastic fiber content of the lateral costotransverse ligament may have no collateral relationship with the morphology of the ligamenta flava, but are conditioned by movements of the ribs. Whereas movements of the upper six joints are limited by virtue of the configuration of their articular surfaces, which are reciprocally curved, on the 7th to 10th joints the articular facets are almost flat and, therefore, allow considerable movements between the ribs and the corresponding transverse processes.

Animals↗
PubMed1990

Ultrastructural and cytochemical study of elastic fibers in the ventral aorta of a teleost, Anguilla japonica.

Previous studies have revealed that amorphous elastin and microfibrils are structural entities of mammalian elastic fibers. Elastin shows a wide phylogenetic distribution, but the presence of elastin-associated microfibrils has not been demonstrated in teleost aorta. Thus, we have ultrastructurally and cytochemically examined elastic fibers in the ventral aorta of eel, a teleost, by utilizing routine uranyl acetate and lead double staining, the tannic acid (pH 7.0)-uranyl acetate (TA-UA) method, elastase en bloc digestion, Thiéry's periodic acid-thiocarbohydrazide-silver proteinate (PA-TCH-SP) method, and the horseradish-peroxidase-labeled concanavalin A (Con A) method. In the ventral aorta of eel, a little ultrastructural difference between elastic fibers in the intima and media and those in the adventitia was noticed, but in either tunic each elastic fiber was basically composed of a "fibrillar core" and surrounding microfibrils. The fibrillar core was a collection of fibrils which showed a tendency to coalesce with each other, and these constituent fibrils were TA-UA positive and elastase-sensitive, representing their nature of elastin. By contrast, microfibrils associated with the fibrillar core were TA-UA negative and elastase-resistant, and their glycoproteinaceous nature was demonstrated by PA-TCH-SP and Con A methods. Thus, this study provides evidence for the presence of elastin-associated microfibrils in teleost aorta. These results are discussed in relation to the topographical difference of elastic fibers in eel aortic wall.

Anguilla↗
PubMed1995

Morphology, histochemistry, and differentiation of the cat's epiglottic cartilage: a supporting organ composed of elastic cartilage, fibrous cartilage, myxoid tissue, and fat tissue.

BACKGROUND: In carnivores, the supporting organ of the epiglottis is usually called "epiglottic cartilage" (EC) although it is composed of elastic cartilage and unilocular fat storing cells. We studied the cat's EC in order to decide whether these fat storing cells are true adipocytes or fat storing (dedifferentiated) chondrocytes. METHODS: ECs were studied in cat embryos at gestation days 40 and 60, in newborn, postnatal, and adult cats. We used classical staining methods, immunohistochemistry, and transmission electron microscopy to identify the different kinds of tissues contributing to the EC and to follow their differentiation. RESULTS: The cat's EC was defined by a layer of coarse collagen fibers representing a tunica albuginea. This tunica covered irregularly formed and irregularly sized areas of elastic cartilage, fibrous cartilage, myxoid tissue, and lobules of unilocular fat cells. All these tissue showed regular morphology. Adipocytes were provided with continuous basal laminae and fat lobules were well supplied with capillaries. Alcianophilia of ground substance was observed in all tissue components but was strongest in elastic cartilage. Most islets of elastic cartilage adhered to the tunica albuginea of the EC at one surface and were connected to the opposite surface by coarse strands of connective tissue traversing the organ. Intercalated areas of fibrous cartilage contained fuchsinophilic collagen bundles. Myxoid tissue was characterized by stellate cells in alcianophilic ground substance with intermingled fuchsinophilic bundles. All kinds of supporting tissues combined with each other without clear demarcation. Immunohistochemistry revealed strong reactivity for S-100 of chondrocytes, myxoid cells, and fat cells. Chondrocytes and myxoid cells also stained for glial fibrillary acidic protein, neurofilament protein 200, and neuron specific enolase. During development, condensation of mesenchymal cells indicated the blastema of the EC at gestation day 40. At day 60, delicate collagen fibrils indicated the future tunica albuginea, faint alcianophilia was noted in the ground substance, and multilocular fat cells were scattered throughout the blastema. At birth, alcianophilia was moderate and multilocular fat cells were numerous. Three weeks after birth, single and grouped unilocular fat cells were seen, alcianophilia of ground substance was prominent, and former blastema cells presented as ramified myxoid cells. Eight weeks after birth, the EC primarily consisted of myxoid tissue, but the first islets of cartilage were seen in the center of myxoid areas. Unilocular fat cells already formed lobules. CONCLUSIONS: These results show that in the cat EC a) differentiation of adipocytes precedes differentiation of all the other tissue components, and b) differentiation of myxoid tissue precedes differentiation of cartilage. It is concluded that myxoid tissue may serve as a precursor of fibrous and elastic cartilage.

Adipocytes↗
PubMed2003

Reduced arterial elasticity in rheumatoid arthritis and the relationship to vascular disease risk factors and inflammation.

OBJECTIVE: Rheumatoid arthritis (RA) is associated with increased rates of cardiovascular disease. Reduced small artery elasticity (SAE) and large artery elasticity (LAE) and increased systemic vascular resistance (SVR) have been found in other high-risk groups. In the present study, we sought to determine whether arterial elasticity was reduced and SVR was increased in RA patients compared with controls matched for coronary artery disease (CAD) status, and to relate the results to vascular disease risk factors, including measures of inflammation. METHODS: Arterial elasticity was assessed by pulse wave analysis in RA patients with (n = 15) and without (n = 38) CAD, and in controls matched 1:1 for age, sex, and CAD status. Vascular risk factors, including high-sensitivity C-reactive protein (hsCRP), soluble vascular cell adhesion molecule 1 (sVCAM-1), and serum amyloid A (SAA) levels, were assessed. RESULTS: SAE and LAE were significantly lower and SVR was significantly higher in RA patients than in controls. RA patients also had higher levels of hsCRP, SAA, and sVCAM-1. SAE and LAE values were inversely correlated with markers of inflammation. Associations of SAE and LAE with RA were independent of conventional risk factors, but were dependent on markers of inflammation. CONCLUSION: Vascular function is abnormal in RA, with reduced SAE and LAE and increased SVR relative to controls. Arterial elasticity is inversely associated with measures of inflammation. These measures may be clinically useful in the detection and monitoring of vascular disease in RA.

Aged↗
PubMed1979

A resonance frequency technique to determine elastic modulus of hydroxyapatite.

A resonance frequency technique was applied to determine the elastic modulus of hydroxyapatite. A Free-Free Vibration Transducer was designed to determine elastic modulus in a longitudinal direction. A Fixed-Free Vibration Transducer was also designed to study elastic modulus of materials were specimens longer than 3 cm in length were not available. Six lots of hydroxyapatite were prepared utilizing the same process. The elastic modulus of hydroxyapatite varied between 3.94 x 10(10) (dyn/cm2) and 6.30 x 10(10) (dyn/cm2) in a longitudinal direction. For the same six lots, it varied between 1.95 x 10(10) (dyn/cm2) and 3.20 x 10(10) (dyn/cm2) in a cross direction. The elastic modulus values of cortical bone from dog tibias, fibulas, and femurs were also determined.

Acoustics↗
PubMed2007

Shape-engineered fibroblasts: cell elasticity and actin cytoskeletal features characterized by fluorescence and atomic force microscopy.

The regulation of cell shape, which determines cell behaviors including adhesion, spreading, migration, and proliferation in an engineered artificial extracellular milieu, is an important task in tissue engineering and in development of functional biomaterials. To deepen the understandings of shape-dependent cell mechanics, the cell elasticity and structural features of the actin cytoskeleton (CSK) were characterized for shape-engineered fibroblasts; round and spindle-shaped cells cultured on photolithographically microprocessed surfaces, employing the cellular microindentation tests and fluorescence observation of actin CSK by the combination of atomic force microscopy (AFM) and fluorescence microscopy (FM). The relationships among cell elasticity, the structural features of actin CSK, and engineered cell shape were analyzed and compared with those of control cells that had been cultured on nonprocessed surfaces (termed naturally extended cells). Results showed that the spindle-shaped cells with sparse or no apical stress fibers (ASFs) exhibited similar stiffness to that of the naturally extended cells with dense ASFs. The elasticity of spindle-shaped cells was affected only slightly by the stress fiber (SF) density, which is in marked contrast to the significant correlation shown between cell elasticity and SF density in naturally extended cells. This result implies that the elasticity of regionally restricted adhesion-surface-induced shape-engineered cells, particularly of highly elongated cells, is affected predominantly by cell shape rather than by structural features of SFs.

3T3 Cells↗
PubMed1999

Elastic fibers of musculoskeletal tissues in bovine Marfan syndrome: a morphometric study.

Bovine Marfan syndrome has all the major pathognomonic, clinical, and pathological features of the human syndrome. To further explore the alterations characterizing Marfan syndrome, musculoskeletal tissues from affected and healthy cattle were subjected to histochemical and histomorphometric analysis. Our findings demonstrated reduced elastic fiber content in the periosteum, capsule, interosseous ligament, and flexor tendons of the metatarsophalangeal joint of affected cattle. The elastic properties of a tissue are supplied by elastic fibers in the extracellular matrix; therefore, their reduced content in articular tissues suggests that these fibers could be functionally incompetent to withstand normal stress, causing a predisposition to joint laxity and dislocation. Moreover, perichondrial-periosteal membranes, which are made of collagen and elastic fibers, are known to affect the growth process of the long bones. The decrease in the number of elastic fibers in these membranes could result in reduced restraint of skeletal growth and explain some skeletal abnormalities of Marfan syndrome (i.e., dolichostenomelic habitus).

Animals↗
PubMed2000

Age, gender, and bone lamellae elastic moduli.

To enhance preventative and therapeutic strategies for metabolic bone diseases and bone fragility disorders, we began to explore the physical properties of bone tissue at the cellular level. Proximal femurs were harvested from 27 cadavera (16 male and 11 female) for in vitro measurement of the mechanical properties. We measured the variations in lamellar-level elastic modulus and hardness in human bone as a function of age and gender to identify microstructural properties responsible for age and gender-related reductions in the mechanical integrity. The lateral femoral necks were examined, and age, gender, height, body mass, and body mass index were not found to correlate with lamellar-level elastic modulus or hardness. This result was consistent for osteonal, interstitial, and trabecular tissue. These data suggest that increased bone mass maintenance, known to occur in heavier individuals, is not accompanied by increases in the lamellar-level elastic modulus or hardness. The independence of elastic modulus and hardness from age and gender suggests that age and gender-related decreases in mechanical integrity do not involve alterations in elastic modulus or hardness of the extracellular matrix. Lamellar-level ultimate, fatigue, and fracture toughness properties should also be investigated. Other factors, such as tissue mass and organization, may also contribute to age and gender-related decreases in the mechanical integrity.

Adult↗
PubMed2007

Elastic liposomes mediated transdermal delivery of an anti-hypertensive agent: propranolol hydrochloride.

One major problem encountered in transdermal drug delivery is the low permeability of drugs through the skin barrier. In the present investigation ultradeformable lipid vesicles, that is, elastic liposomes were prepared incorporating propranolol hydrochloride for enhanced transdermal delivery. Elastic liposomes bearing propranolol hydrochloride were prepared by conventional rotary evaporation method and characterized for various parameters including vesicles shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, turbidity, and in vitro drug release. In vitro flux, enhancement ratio (ER), and release pattern of propranolol hydrochloride were calculated for transdermal delivery. In vivo study conducted on male albino rats (Sprague Dawley) was also taken as a measure of performance of elastic liposomal, liposomal, and plain drug solution. The better permeation through the skin was confirmed by confocal laser scanning microscopy (CLSM). Results indicate that the elastic liposomal formulation for transdermal delivery of propranolol hydrochloride provides better transdermal flux, higher entrapment efficiency, ability as a self-penetration enhancer and effectiveness for transdermal delivery as compared to liposomes.

Administration, Cutaneous↗
PubMed1986

Reactivity of enprostil stereoisomers in soft elastic gelatin capsules.

Enprostil (methyl 7-[(1R*,2R*,3R*)-3-hydroxy-2-[(E)-(3R*)-3-hydroxy-4-phenoxy-1-butenyl]- 5-oxocyclopentyl]-4,5-heptadienoate), a gastric acid secretion inhibitor and potent anti-ulcer drug, is formulated as a propylene carbonate solution which is filled into soft elastic gelatin capsules. The drug molecule features two unresolved asymmetric carbon atoms, and synthesis yields an equimolar mixture of four different optical isomers (two diastereomeric pairs of enantiomers). The objective of this study was to establish the degree to which enprostil does or does not degrade stereoselectively in the soft elastic gelatin capsule formulation. Accordingly, we developed an HPLC method capable of resolving enprostil diastereoisomers and applied the method to determining reaction rates of enprostil in soft elastic gelatin capsules maintained at 40 degrees C. The study included three soft elastic gelatin capsule lots: the first two contained an equimolar mixture of all four enprostil enantiomers; and the third contained an equimolar mixture of two individual diastereoisomers of known optical purity. Comparing enprostil degradation rates in the three capsule lots showed that reactivity ratios in all cases were (within the limits of experimental uncertainty) equal to unity. This observation conclusively excludes the possibility of significant enantioselectivity for enprostil degradation in the soft elastic gelatin capsule formulation. We also report kinetic equations for the general case of relating stereospecific reactivity ratios to drug product shelf life when drug concentrations are monitored with nonstereoselective analytical techniques.

Capsules↗
PubMed2004

In vivo elasticity measurements of extremity skeletal muscle with MR elastography.

MR elastography (MRE) has been shown to be capable of non-invasively measuring tissue elasticity even in deep-lying regions. Although limited studies have already been published examining in vivo muscle elasticity, it is still not clear over what range the in vivo elasticity values vary. The present study intends to produce further information by examining four different skeletal muscles in a group of 12 healthy volunteers in the age range of 27-38 years. The examinations were performed in the biceps brachii, the flexor digitorum profundus, the soleus and the gastrocnemius. The average shear modulus was determined to be 17.9 (+/- 5.5), 8.7 (+/- 2.8), 12.5 (+/- 7.3) and 9.9 (+/- 6.8) kPa for each muscle, respectively. To ascertain the reproducibility of the examination, the stiffness measurements in two volunteers were repeated seven times for the biceps brachii. These examinations yielded a mean shear modulus of 11.3 +/-.7 and 13.3 +/- 4.7 kPa for the two subjects. For elasticity reconstruction, an automated reconstruction algorithm is introduced which eliminates variation due to subjective manual image analysis. This study yields new information regarding the expected variation in muscle elasticity in a healthy population, and also reveals the expected variability of the MRE technique in skeletal muscle.

Adult↗