Polypropelene-mesh properties and type of anchoring do not influence strength of parietal ingrowth.

PURPOSE: In laparoscopic ventral hernia repair, parietal ingrowth of the mesh is of crucial importance. Until significant ingrowth occurs integrity of the repair depends solely on mesh overlap and anchoring device. Relatively few studies have addressed the effect of mesh properties and anchoring device on long-term parietal ingrowth. METHODS: In 20 sheep, using laparoscopy, we inserted two different polypropylene-based meshes, Physiomesh™ and Ventralight™ ST, anchored with Protack™, SecureStrap™, or Glubran™. After 6 and 12 months, 10 sheep at each time point were euthanized, and we harvested the meshes with corresponding fascia. Mesh with fascia was attached on an Alwetron™ materials testing machine and pulled apart obtaining the peel-off energy (kilojoule (kJ)). RESULTS: The strength of parietal ingrowth at 6 months was 5.99 ± 0.54 kJ (mean ± SEM), 4.94 ± 0.54 kJ and 7.35 ± 0.55 kJ when anchored with Protack™, Glubran™, or SecureStrap™, respectively. At 6 months, the strength of parietal ingrowth of SecureStrap™ was significantly higher than Glubran™ (p = 0.04). No significant difference was seen between any other combinations. Parietal ingrowth at 12 months was 7.05 ± 0.56 kJ, 7.55 ± 0.54 kJ, and 5.73 ± 0.54 kJ when anchored with Protack™, Glubran™, and SecureStrap™, respectively. No significant difference in strength of parietal ingrowth was seen between the three types of anchoring, (p = 1.00, p = 1.00, and p = 0.29). CONCLUSIONS: At 12 months, the strength of parietal ingrowth was the same for all comparisons. The two polypropylene meshes showed equal strength of parietal ingrowth independent of mesh properties and anchoring devices used.

Mesh shrinkage depends on mesh properties and anchoring device: an experimental long-term study in sheep.

PURPOSE: The choice of mesh and anchoring device in laparoscopic ventral hernia repair is controversial. Clinically important long-term properties of mesh and anchoring device such as mesh shrinkage have been sparsely investigated. Furthermore, the effect of various anchoring devices on mesh properties has never been examined. METHODS: In 20 sheep, using laparoscopy, we inserted three PhysiomeshTM (large pore, lightweight) and three VentralightTMST (small pore, mediumweight), anchored with ProTackTM, SecurestrapTM or GlubranTM, respectively. After 6 and 12 months, 10 sheep at each time-point, we euthanized the animals, harvested the meshes with fascia, and measured the exact size and area of the mesh, expressing mesh shrinkage as a percentage of the initial area. RESULTS: The shrinkage of PhysiomeshTM was 35.7 %, 23.8 % and 17.7 % when anchored with ProtackTM, GlubranTM or SecurestrapTM, respectively. Shrinkage with ProtackTM was significantly higher than with either GlubranTM or SecurestrapTM, respectively (p<0.01 and p<0.01). The shrinkage of VentralightTMST was 19.3 %, 22.2 % and 19.6 % when anchored with ProtackTM, GlubranTM and SecurestrapTM, respectively (p>0.05 for all pairwise comparisons). Overall shrinkage of PhysiomeshTM anchored with ProtackTM was significantly higher for all comparisons (p<0.01). CONCLUSION: Our results suggest that mesh shrinkage in sheep takes place within 6 months after implantation. A significant interaction between mesh and type of anchoring indicates that shrinkage may depend on both mesh properties and anchoring device. The results of the current study imply that the combined effect of mesh and anchoring device should be evaluated in future studies.

The giraffe kidney tolerates high arterial blood pressure by high renal interstitial pressure and low glomerular filtration rate.

BACKGROUND: The tallest animal on earth, the giraffe (Giraffa camelopardalis) is endowed with a mean arterial blood pressure (MAP) twice that of other mammals. The kidneys reside at heart level and show no sign of hypertension-related damage. We hypothesized that a species-specific evolutionary adaption in the giraffe kidney allows normal for size renal haemodynamics and glomerular filtration rate (GFR) despite a MAP double that of other mammals. METHODS: Fourteen anaesthetized giraffes were instrumented with vascular and bladder catheters to measure glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Renal interstitial hydrostatic pressure (RIHP) was assessed by inserting a needle into the medullary parenchyma. Doppler ultrasound measurements provided renal artery resistive index (RI). Hormone concentrations as well as biomechanical, structural and histological characteristics of vascular and renal tissues were determined. RESULTS: GFR averaged 342 ± 99 mL min(-1) and ERPF 1252 ± 305 mL min(-1) . RIHP varied between 45 and 140 mmHg. Renal pelvic pressure was 39 ± 2 mmHg and renal venous pressure 32 ± 4 mmHg. A valve-like structure at the junction of the renal and vena cava generated a pressure drop of 12 ± 2 mmHg. RI was 0.27. The renal capsule was durable with a calculated burst pressure of 600 mmHg. Plasma renin and AngII were 2.6 ± 0.5 mIU L(-1) and 9.1 ± 1.5 pg mL(-1) respectively. CONCLUSION: In giraffes, GFR, ERPF and RI appear much lower than expected based on body mass. A strong renal capsule supports a RIHP, which is >10-fold that of other mammals effectively reducing the net filtration pressure and protecting against the high MAP.

Work instability in rheumatoid arthritis patients from Argentina: prevalence and associated factors.

To determine the prevalence of and associated factors to work instability (WI) in rheumatoid arthritis (RA) Argentinean patients. Observational cross-sectional study that assessing employment status in currently working RA patients. They answered the validated version of RA work instability scale (RA-WIS). High-risk WI was considered when RA-WIS was ≥17. Factors associated with high-risk WI were examined by univariable and multivariable analysis. Four-hundred and fifty RA patients were enrolled; of these, 205 patients were currently employed, but only 172 have completed questionnaires required [RA-WIS and health assessment questionnaire (HAQ-A)]. Their mean age was 49.3 ± 10.8 years; 81.3 % were female; and their mean disease duration was 8.1 ± 7.2 years. Fifty-two percent of patients were doing manual work. The mean RA-WIS score was 11.4 ± 6.8, and 41 % of patients had a high-risk WI. High-risk WI was associated with radiographic erosions (p < 0.001) and HAQ-A >0.87 (p < 0.001) in the univariable analysis, whereas in the multivariable logistic regression analysis the variables associated with a high-risk WI were as follows: HAQ-A >0.87 [odds ratio (OR) 12.31; 95 % CI 5.38-28.18] and the presence of radiographic erosions (OR 4.848; 95 % CI 2.22-10.5). In this model, having a higher monthly income (OR 0.301; 95 % CI 0.096-0.943) and a better functional class (OR 0.151; 95 % CI 0.036-0.632) were protective. Forty-one percent of RA working patients had high-risk WI. The predictors of high RA-WIS were HAQ-A ≥0.87 and radiographic erosions, whereas having a better functional class and have higher incomes were protective.

No effect of risedronate on articular cartilage damage in the Dunkin Hartley guinea pig model of osteoarthritis.

OBJECTIVES: To investigate whether treatment with a bisphosphonate would influence the subchondral bone plate stiffness and the development of cartilage damage in Dunkin Hartley guinea pigs, which develop osteoarthritis (OA) spontaneously. METHOD: Fifty-six 3-month-old male Dunkin Hartley guinea pigs were randomized into a baseline group and six groups receiving either the bisphosphonate risedronate (30 µg/kg) or vehicle five times a week for 6, 12, or 24 weeks. The medial condyle of the right stifle joint was investigated by histology, using the Osteoarthritis Research Society International (OARSI) score, along with static and dynamic histomorphometry. The subchondral bone plate of the left tibia was tested mechanically with indentation testing. Degradation products of C-terminal telopeptides of type II collagen (CTX-II) were measured in serum. RESULTS: The OARSI score did not differ between risedronate-treated and control animals at any time point. The fraction of bone surfaces covered with osteoclasts (Oc.S/BS) was significantly suppressed in risedronate-treated animals at all time points, as were the fractions of mineralizing surfaces (MS/BS) and osteoid-covered surfaces (OS/BS), and also serum CTX-II. This was accompanied by a significant increase in the epiphyseal content of calcified tissue and in the thickness of the subchondral bone plate. However, this did not result in a stiffer subchondral bone at any time point. DISCUSSION: The risedronate treatment inhibited osteoclastic resorption of calcified cartilage in the primary spongiosa under the epiphyseal growth plate, explaining the risedronate-mediated decrease in CTX-II. Moreover, the serum CTX-II level was not related to the OA-induced articular cartilage degradation seen in this model. CONCLUSIONS: Risedronate did not influence the OARSI score and subchondral plate stiffness, but decreased serum CTX-II in Dunkin Hartley guinea pigs.

Relationship between articular cartilage damage and subchondral bone properties and meniscal ossification in the Dunkin Hartley guinea pig model of osteoarthritis.

OBJECTIVES: To describe the age-related changes of articular cartilage, subchondral bone morphology, and stiffness. Furthermore, to investigate whether subchondral bone histological and mechanical properties and meniscal histological properties are related to articular cartilage damage in the Dunkin Hartley guinea pig model of osteoarthritis (OA). METHODS: Forty male Dunkin Hartley guinea pigs aged 2, 6, 9, and 12 months were studied. The right stifle joints and the left menisci were embedded undecalcified and the tibial articular cartilage and subchondral bone and the menisci were examined using histology. The stiffness of the left tibial subchondral bone was determined with indentation testing. RESULTS: The Osteoarthritis Research Society International (OARSI) grade of the osteoarthritic cartilage lesions of the medial (p < 0.001) and lateral (p < 0.001) condyle and the ossification of the medial (p < 0.001) and lateral (p < 0.001) meniscus increased significantly with age and was significantly more pronounced at the medial condyle than at the lateral condyle. The grade of the osteoarthritic cartilage lesions was significantly correlated (r = 0.78, p < 0.001) with the meniscal ossification, weakly correlated (r = 0.34, p < 0.007) with the subchondral bone plate thickness, and not correlated with the subchondral bone density (r = -0.010, p = 0.94) and the subchondral bone stiffness (r = -0.13, p = 0.30). CONCLUSION: The meniscal ossification observed in Dunkin Hartley guinea pigs may play an important role in the pathogenesis of OA in these animals.

The anabolic effect of PTH on bone is attenuated by simultaneous glucocorticoid treatment.

Glucocorticoids (GC) are used for the treatment of a wide spectrum of diseases because of their potent anti-inflammatory and immunosuppressive effects, and they are serious and common causes of secondary osteoporosis. Administration of intermittent parathyroid hormone (PTH) may induce formation of new bone and may counteract the bone loss induced by GC treatment. Effects of simultaneous PTH and GC treatment were investigated on bone biomechanics, static and dynamic histomorphometry, and bone metabolism. Twenty-seven-month-old female rats were divided randomly into the following groups: baseline, vehicle, PTH, GC, and PTH + GC. PTH (1-34) 25 mug/kg and GC (methylprednisolone) 2.5 mg/kg were injected subcutaneously each day for a treatment period of 8 weeks. The rats were labeled with fluorochromes 3 times during the experiment. Bone sections were studied by fluorescence microscopy. The PTH injections resulted in a 5-fold increase in cancellous bone volume. At the proximal tibia, PTH induced a pronounced formation of new cancellous bone which originated from the endocortical bone surfaces and from thin trabeculae. Formation and modeling of connections between trabeculae were observed. Similar but less pronounced structural changes were seen in the PTH + GC group. The compressive strength of the cancellous bone was increased by 6-fold in the PTH group compared with the vehicle group. GC partially inhibited the increase in compressive strength induced by PTH. Concerning cortical bone, PTH induced a pronounced increase in the endocortical bone formation rate (BFR) and a smaller increase in periosteal BFR. The combination of PTH + GC resulted in a partial inhibition of the PTH-induced increase in bone formation. Serum-osteocalcin was increased by 65% in the PTH group and reduced by 39% in the GC group. The pronounced anabolic effect of PTH injections on the endocortical and trabecular bone surfaces and less pronounced anabolic effect on periosteal surfaces were partially inhibited, but not prevented, by simultaneous GC treatment in old rats. Both cortical and cancellous bone possessed full mechanical competence after treatment with PTH + GC.

Age-related three-dimensional microarchitectural adaptations of subchondral bone tissues in guinea pig primary osteoarthrosis.

We explored potential mechanisms of the microarchitectural adaptations of subchondral bone tissues in a guinea pig primary osteoarthrosis (OA) model. We harvested proximal tibiae of male Dunkin-Hartley (Charles River strain) guinea pigs at 3, 6, 9, 12, and 24 months of age (10 in each group). These proximal tibiae were scanned by micro-computed tomography to quantify the three-dimensional microarchitecture of the subchondral plate, cancellous bone, and cortical bone. Subsequently, the bones were compression-tested to determine their mechanical properties. Furthermore, bone collagen, bone mineral, and bone density were determined. Mankin's score corresponded to OA grading from absent or minimal cartilage degeneration in 3-month-old to severe degeneration in 24-month-old guinea pigs. In young guinea pigs, the volume fraction and thickness of the subchondral plate markedly increased from 3 to 6 months, whereas the volume fraction of the subchondral cancellous bone displayed an initial decline followed by an increase. With age, the trabeculae increased in thickness, changed from rod-like to plate-like, and became more axially oriented. An increasing ratio of bone collagen to mineral in subchondral bone indicated undermineralized bone tissues. In subchondral cancellous bone, Young's modulus was maximal at 6 months of age, whereas ultimate stress and failure energy showed a gradual increase with age. The findings show pronounced alterations of the microarchitecture and bone matrix composition of the subchondral bone. These alterations did not appear to follow the same pattern as in normal aging and may have different influences on the resulting mechanical properties.

Effects of short-term alendronate treatment on the three-dimensional microstructural, physical, and mechanical properties of dog trabecular bone.

The bisphosphonate, alendronate, is well known for its potent inhibition of osteoclast-mediated bone resorption. It has been used clinically for the treatment of osteoporosis and has also recently been used to reduce osteolysis around prostheses in a canine revision model of implant loosening (femoral condyle). In this study, the effects of alendronate on trabecular bone properties were assessed in dogs at an oral dose of 0.5 mg/kg per day over a 12 week period, and compared with control dogs. Cubic cancellous bone specimens were produced from lumbar vertebrae (L-1 and L-2) and bilateral proximal humeri. These specimens were scanned using a high-resolution microcomputed tomography (micro-CT) system. From accurate data sets, three-dimensional microstructural properties were calculated and physical and mechanical properties were determined. Treatment with alendronate increased bone volume fraction by 9.5%, 7.7%, 7.4%, and 18.4%, respectively, in L-1, L-2, humeral greater tuberosity, and humeral head trabecular bone. In the lumbar vertebrae, the alendronate-treated trabeculae were thicker and lower in bone surface-to-volume ratio. In the greater tuberosity, the alendronate-treated trabeculae were thicker, lower in bone surface-to-volume ratio, and less anisotropic. In the humeral head, the alendronate-treated trabeculae were thicker, less anisotropic, lower in surface density, and showed decreased trabecular separation. Alendronate significantly increased apparent density and collagen density in the lumbar vertebrae and humeral heads, and significantly decreased collagen concentration in the vertebrae. In the lumbar vertebrae, Young's modulus in the cephalocaudal direction, ultimate stress, and failure energy were significantly increased in the alendronate-treated group. The changes in mechanical properties in the humeral head trabecular bone were similar to those seen in the lumbar vertebrae. Our results demonstrate that alendronate increases the mechanical properties of healthy canine trabecular bone after short-term treatment. The physical and microstructural changes of trabecular bone are consistent with the significantly increased mechanical properties.

Dietary supplementation with methionine and homocysteine promotes early atherosclerosis but not plaque rupture in ApoE-deficient mice.

Hyperhomocysteinemia is an independent risk factor for atherothrombosis. However, causality is unproven, and it remains unknown whether hyperhomocysteinemia promotes atherosclerosis, plaque rupture, and/or thrombosis. We evaluated the short- and long-term effects of hyperhomocysteinemia on plaque size and structure in 99 atherosclerosis-prone apolipoprotein E-deficient mice. Hyperhomocysteinemia was induced by methionine (Met) or homocysteine (HcyH) supplementation: low Met (+11 g Met/kg food), high Met (+33 g Met/kg food), low HcyH (0.9 g HcyH/L drinking water), and high HcyH (1.8 g HcyH/L drinking water). Met and HcyH supplementation significantly raised plasma total homocysteine levels by 4- to 16-fold above those observed in mice fed a control diet (up to 146.1 micromol/L). Compared with controls, aortic root plaque size was significantly larger in supplemented groups after 3 months (56% and 173% larger in high-Met and high-HcyH, respectively) but not after 12 months. Hyperhomocysteinemia was associated with an increase in the amount of collagen in plaques after both 3 and 12 months. Mechanical testing of the tail tendons revealed no weakening of collagen after 12 months of hyperhomocysteinemia. Many plaques in both control and supplemented mice appeared rupture prone morphologically, but all aortic root plaques and all but 1 coronary plaque had an intact surface without rupture or thrombosis. Thus, diet-induced hyperhomocysteinemia promotes early atherosclerosis and plaque fibrosis but does not, even in the long term, weaken collagen or induce plaque rupture.

Bone density does not reflect mechanical properties in early-stage arthrosis.

Subchondral cancellous bone specimens were removed from 10 human postmortem early-stage arthrotic proximal tibiae (mean age 73 (63-81) years) and 10 age- and gender-matched normal proximal tibiae. The early-stage arthrosis was confirmed histologically and the specimens were divided into 4 groups: medial arthrosis, lateral control, normal medial and normal lateral controls. The specimens were tested in compression to determine mechanical properties and then physical/compositional properties. Compared to the normal medial control, we found reductions in ultimate stress, Young's modulus, and failure energy, and an increase in ultimate strain of arthrotic cancellous bone. Bone volume fraction, apparent density, apparent ash density, and collagen density were higher in cancellous bone with arthrosis, but no differences were found in tissue density, mineral and collagen concentrations between arthrotic cancellous bone and the 3 controls. None of the mechanical properties of arthrotic cancellous bone could be predicted by the physical/compositional properties measured. The increase in bone tissue in early-stage arthrotic cancellous bone did not make up for the loss of mechanical properties, which suggests a deterioration in the quality of arthrotic cancellous bone.

Properties of growing trabecular ovine bone. Part I: mechanical and physical properties.

Our aim was to determine the relationship between age and the mechanical and physical properties of trabecular bone, to describe the patterns in which the variations in these properties take place, and to investigate the influence of the physical properties on the mechanical characteristics of trabecular bone during growth. We used 30 lambs in three age groups and 20 sheep in two age groups. Cubes of subchondral bone were cut from the proximal tibia according to a standardised protocol. We performed non-destructive compression tests of the specimens in three orthogonal directions and compression tests to failure in the axial direction. The physical properties of the specimens were also determined. The data were correlated with age and compared in skeletally immature and mature animals. Multiple regression analyses were performed between the mechanical and the physical properties. Age correlated positively with elastic modulus, bone strength, energy absorption to failure, elastic energy, mechanical anisotropy ratio, tissue density, apparent density, apparent ash density, and bone mineral content, and inversely with ultimate strain, viscoelastic energy absorption, relative energy loss, the collagen content of bone and the percentage porosity. The values of all variables were significantly different in the skeletally mature and immature groups. The apparent density of trabecular bone tissue was found to be the major predictor of its compressive mechanical properties. Together with the content of bone muscle and bone collagen, the apparent density could explain 84% of the variation in the elastic modulus, whereas only a small portion of the variation in ultimate strain could be explained by the variation in apparent density.

Increased amounts of collagenase and gelatinase in porcine myocardium following ischemia and reperfusion.

We studied the presence of collagen degrading enzymes (matrix metalloproteinases, MMPs) in porcine myocardium following ischemia and late reperfusion. In nine pigs, left anterior descending coronary artery was occluded for 6 h followed by reperfusion for 3 h. Six pigs without coronary occlusion served as controls. After the reperfusion period, transmural biopsies from the anterior (ischemic zone) and posterior wall (non-ischemic myocardium) in the left ventricle were obtained and extracted. Heparin-Sepharose isolated components in extracts were analysed for collagenase (triple-helical collagen degradation) and gelatinase activity (zymography). Immunohistochemistry using anti-human (MMP-1, MMP-2, MMP-9, and fibronectin) antibodies was performed on additional biopsies. Collagenase (MMP-1) and gelatinases (MMP-2, MMP-9) could be demonstrated in the extracts of non-ischemic myocardium from ischemic/reperfused as well as control pigs and MMP-1 and MMP-9 activity was found to be increased in ischemic/reperfused myocardium compared with non-ischemic myocardium. In ischemic/reperfused myocardium from live pigs investigated, myocyte necrosis could be confirmed by fibronectin immunoreaction in myocytes and MMP-1 and MMP-9 immunoreactions were increased. MMP-9 was present in cells likely to be infiltrating leukocytes in a patchy distribution throughout the ischemic myocardium. Quite coincident with MMP-9 positive cells, MMP-1 immunoreaction appeared in necrotic myocytes, in addition to reactions observed in vessel walls, endo- and epicardium, and extracellular matrix in non-ischemic myocardium. Thus, the results showed increased amounts of collagenase (MMP-1) and gelatinase (MMP-9) in ischemic/ reperfused myocardium, indicating the appearance of increased amounts of collagen degrading enzymes very early following ischemia and late reperfusion.

Thermal and mechanical stability of the lens capsule.

PURPOSE: Several procedures in cataract surgery carry the risk of high temperature increases in the capsular bag. The present study was undertaken to determine the shrinkage temperature of the human lens capsule and to investigate the effect of temperature on the mechanical behavior of the lens capsule. METHOD: Thermal-shrinkage characteristics of the lens capsule were determined during gradual heating of circular specimens (2 mm in diameter) prepared from anterior lens capsules from 25 human donors, ranging in age from 20 to 98 years. Uniaxial mechanical testing was carried out at 22 degrees C, 36 degrees C and 61 degrees C on ring-shaped test specimens prepared from anterior lens capsules from 5- to 6-month-old pigs. RESULTS: The mean shrinkage temperature (Ts) for the human lens capsule was 51.5 degrees C (range 49.3-54.3) and the mean shrinkage area in percent of the original area (AST) was 49% (36-66). Ts was significantly associated with the age of the donors and decreased 0.1 degree C per year until age 65 after which Ts was found to increase. AST showed no association with age. The mechanical effect of temperatures below the shrinkage temperature was modest. The capsule became slightly more extensible with increasing temperature. The effect of temperatures above the shrinkage temperature was an increased ultimate strain, a reduced ultimate stiffness and a slightly reduced ultimate stress. CONCLUSION: Thermal stability of the human lens capsule (type IV collagen) seems to be considerably lower than that of fibrous connective tissue (type I collagen). A potential risk of capsular shrinking has to be taken into account when the capsule is exposed to thermal stress during cataract surgery.

Thermal stability of bone collagen as an indicator of bone turnover in gonadectomized and multiparous rats.

Previous findings indicate that the thermal stability of bone collagen is related to age. In this study, collagen from rat bone with reported different turnover rates was investigated. Cortical and trabecular bone from femur were obtained from intact, ovariectomized, orchidectomized and multiparous breeder rats. Thermal stabilities of fibrillar collagen in decalcified bone matrix and molecular collagen obtained by pepsin treatment were measured as shrinkage (Ts) and 'melting' temperature (Tm), respectively. Both Ts and Tm of cortical collagen from intact female rats decreased in parallel with age as previously found in male rats indicating that Ts and Tm measurements are interchangeable techniques in characterizing the thermal stability of bone collagen. Tm of trabecular collagen from intact rats decreased with age, however, with a decay only one-third of that for cortical collagen. The different rates possibly reflect different ages of collagen due to remodeling activity present in trabecular and minimal in cortical bone. Compared with control rats the Tm of trabecular collagen from gonadectomized and multiparous rats with a reported increased trabecular turnover rate was elevated, whereas only minor variations in Tm of cortical collagen were found. In conclusion, the thermal stability of bone collagen decreases with the age of the collagen. Increased bone turnover implies elevated thermal stability of bone collagen. Thus, thermal stability of bone collagen appears to be an indicator of bone turnover.

Age variations in the properties of human tibial trabecular bone.

We tested in compression specimens of human proximal tibial trabecular bone from 31 normal donors aged from 16 to 83 years and determined the mechanical properties, density and mineral and collagen content. Young's modulus and ultimate stress were highest between 40 and 50 years, whereas ultimate strain and failure energy showed maxima at younger ages. These age-related variations (except for failure energy) were non-linear. Tissue density and mineral concentration were constant throughout life, whereas apparent density (the amount of bone) varied with ultimate stress. Collagen density (the amount of collagen) varied with failure energy. Collagen concentration was maximal at younger ages but varied little with age. Our results suggest that the decrease in mechanical properties of trabecular bone such as Young's modulus and ultimate stress is mainly a consequence of the loss of trabecular bone substance, rather than a decrease in the quality of the substance itself. Linear regression analysis showed that collagen density was consistently the single best predictor of failure energy, and collagen concentration was the only predictor of ultimate strain.

Mast cells in cervical ripening--an immunohistochemical and biomechanical study in rats.

Cervical ripening purportedly involves different cell types and mediators normally associated with inflammatory reactions. The purpose of the present study was to determine the presence of mast cells in rat cervices during spontaneous and antigestagen induced ripening and to test whether a mast cell stabilizer was able to inhibit the antigestagen induced cervical ripening. Immunohistochemical examinations demonstrated an increased number of mast cells in pregnant and intrapartum rats. Furthermore, mast cell degranulation was found to be prominent after antigestagen treatment. The degranulation was completely abolished by co-treatment with the mast cell stabilizer. Biomechanical analysis showed that the mast cell stabilizer also inhibited the antigestagen induced cervical ripening to some extent. Thus, it is concluded that mast cell stabilizers might constitute a new approach in the treatment of preterm cervical ripening.

Ischemia and reperfusion of the porcine myocardium: effect on collagen.

We studied the effect of acute myocardial infarction and late reperfusion on myocardial collagen in a closed chest porcine model, to investigate if any collagen degradation could be detected in blood samples and myocardium. Sixteen 60-80 kg pigs were used with six animals serving as controls and 10 submitted to ischemia-reperfusion. In the ischemia-reperfusion group the left anterior descending coronary artery was occluded for 6 h by inflation of a percutaneous transluminal coronary angioplasty balloon followed by reperfusion for 3 h. Blood samples were taken from the aorta and the coronary sinus and analyzed for creatine kinase and collagen degradation products, i.e. the N-terminal propeptide of procollagen type III (PIIINP) and C-terminal pyridinoline cross-linked telopeptide of collagen type I (ICTP). Myocardial tissue samples were analyzed for content of hydroxyproline, collagen volume fraction and amount of extractable PIIINP/dry weight. Transmission electron microscopy of biopsies was performed to evaluate myocytes and collagen structure outside and within the infarct zone. Creatine kinase showed a statistically significant increase during ischemia and reperfusion but we found no evidence of release of collagen degradation products either during ischemia or reperfusion compared with control. Myocardial content of hydroxyproline, collagen volume fraction and extractable PIIINP/dry weight did not differ between groups. Transmission electron microscopy of biopsies from the infarct zone showed myocyte damage but no visible evidence of collagen degradation when photos were evaluated blindly. In this porcine model of acute myocardial infarction and late reperfusion no release of collagen degradation products from the myocardium or any decrease in or damage to myocardial collagen was detected.

Insulin-like growth factor I as a predictor of cortical bone mass in a long-term study of ovariectomized and estrogen-treated rats.

The relationship between serum insulin-like growth factor I (IGF-I) and cortical bone mass, formation and resorption and length of bone in a long-term experiment on intact, ovariectomized and estrogen-treated/substituted rats was studied by using multiple linear regression analysis. The study comprised intact rats killed at 2, 6, 9, 12, 15, and 24 months of age, rats ovariectomized 6 months old and killed at 9, 12, 15, and 24 months of age, and intact and ovariectomized rats treated with a low dose of estrogen for 8 months before they were killed at 24 months of age. Serum IGF-I, bone length and total, subperiosteal and subendocortical bone mass in mid-diaphyseal cross sections of the femur were determined. Changes in the latter two variables, respectively, represent the net result of subperiosteal bone formation and subendocortical bone resorption. Multiple linear regression analysis showed that IGF-I was a positive determinant of cortical bone mass and subperiosteal bone formation. In aged rats, IGF-I was also a positive determinant of bone length, whereas IGF-I was not found to be a determinant of subendocortical bone resorption. The analyses showed that long-term treatment of aged rats with a low dose of estrogen had a dual effect on cortical bone by inhibiting subperiosteal formation and subendocortical resorption. The results revealed a relationship between endogenous circulating IGF-I and local anabolic actions of the growth factor in bones. Thus, IGF-I may be a valuable serum marker of cortical bone formation and length of long bones when considering estrogen-depleted and estrogen-treated rats.