Percentage Of Collagen Content Research Articles

Tibial Cortex Transverse Transport Facilitates Severe Diabetic Foot Wound Healing via HIF-1α-Induced Angiogenesis.

Management of severe diabetic foot ulcers (DFUs) remains challenging. Tibial cortex transverse transport (TTT) facilitates healing and limb salvage in patients with recalcitrant DFUs. However, the underlying mechanism is largely unknown, necessitating the establishment of an animal model and mechanism exploration. Severe DFUs were induced in rats, then assigned to TTT, sham, or control groups (n=16/group). The TTT group underwent a tibial corticotomy, with 6 days each of medial and lateral transport; the sham group had a corticotomy without transport. Ulcer healing was assessed through Laser Doppler, CT angiography, histology, and immunohistochemistry. Serum HIF-1α, PDGF-BB, SDF-1, and VEGF levels were measured by ELISA. The TTT group showed lower percentages of wound area, higher dermis thickness (all p < 0.001 expect for p = 0.001 for TTT vs Sham at day 6) and percentage of collagen content (all p < 0.001) than the other two groups. The TTT group had higher perfusion and vessel volume in the hindlimb (all p < 0.001). The number of CD31+ cells (all p < 0.001) and VEGFR2+ cells (at day 6, TTT vs Control, p = 0.001, TTT vs Sham, p = 0.006; at day 12, TTT vs Control, p = 0.003, TTT vs Sham, p = 0.01) were higher in the TTT group. The activity of HIF-1α, PDGF-BB, and SDF-1 was increased in the TTT group (all p < 0.001 except for SDF-1 at day 12, TTT vs Sham, p = 0.005). The TTT group had higher levels of HIF-1α, PDGF-BB, SDF-1, and VEGF in serum than the other groups (all p < 0.001). TTT enhanced neovascularization and perfusion at the hindlimb and accelerated healing of the severe DFUs. The underlying mechanism is related to HIF-1α-induced angiogenesis.

Radiation induced changes in profibrotic markers in the submental muscles and their correlation with tongue movement.

Swallowing impairment is a major complication of radiation treatment for oropharyngeal cancers. Developing targeted therapies that improve swallowing outcomes relies on an understanding of the mechanisms that influence motor function after radiation treatment. The purpose of this study was to determine whether there is a correlation between radiation induced changes in tongue movement and structural changes in irradiated submental muscles, as well as assess other possible causes for dysfunction. We hypothesized that a clinically relevant total radiation dose to the submental muscles would result in: a) quantifiable changes in tongue strength and displacement during drinking two months post treatment; and b) a profibrotic response and/or fiber type transition in the irradiated tissue. Sprague-Dawley adult male rats received radiation to the submental muscles at total dose-volumes known to provoke dysphagia in humans. A clinical linear accelerator administered 8 fractions of 8Gy for a total of 64Gy. Comparisons were made to sham-treated rats that received anesthesia only. Swallowing function was assessed using videofluoroscopy and tongue strength was analyzed via force lickometer. TGFβ1 expression was analyzed via ELISA. The amount of total collagen was analyzed by picrosirius red staining. Immunofluorescence was used to assess fiber type composition and size. Significant changes in licking function during drinking were observed at two months post treatment, including a slower lick rate and reduced tongue protrusion during licking. In the mylohyoid muscle, significant increases in TGFβ1 protein expression were found post radiation. Significant increases in the percentage of collagen content were observed in the irradiated geniohyoid muscle. No changes in fiber type expression were observed. Results indicate a profibrotic transition within the irradiated swallowing muscles that contributes to tongue dysfunction post-radiation treatment.

Consistency of Pituitary Adenoma: Prediction by Pharmacokinetic Dynamic Contrast-Enhanced MRI and Comparison with Histologic Collagen Content.

Simple SummaryTranssphenoidal resection of hard pituitary adenomas have a particularly high risk of residual tumor and complications. Therefore, prediction of tumor consistency is valuable for planning pituitary adenoma surgery. We prospectively examined whether quantitative pharmacokinetic analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is useful for predicting consistency of pituitary adenoma in 49 participants. We found that the measure of volume of extravascular extracellular space per unit volume of tissue derived from DCE-MRI could predict the consistency of pituitary adenomas. Furthermore, the volume of extravascular extracellular space per unit volume of tissue was significantly positively correlated with histopathologic collagen content of the adenoma. Our results suggest that volume of extravascular extracellular space per unit volume of tissue derived from quantitative pharmacokinetic analysis of DCE-MRI has a predictive value for consistency of pituitary adenomas.Prediction of tumor consistency is valuable for planning transsphenoidal surgery for pituitary adenoma. A prospective study was conducted involving 49 participants with pituitary adenoma to determine whether quantitative pharmacokinetic analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is useful for predicting consistency of adenomas. Pharmacokinetic parameters in the adenomas including volume of extravascular extracellular space (EES) per unit volume of tissue (ve), blood plasma volume per unit volume of tissue (vp), volume transfer constant between blood plasma and EES (Ktrans), and rate constant between EES and blood plasma (kep) were obtained. The pharmacokinetic parameters and the histologic percentage of collagen content (PCC) were compared between soft and hard adenomas using Mann–Whitney U test. Pearson’s correlation coefficient was used to correlate pharmacokinetic parameters with PCC. Hard adenomas showed significantly higher PCC (44.08 ± 15.14% vs. 6.62 ± 3.47%, p < 0.01), ve (0.332 ± 0.124% vs. 0.221 ± 0.104%, p < 0.01), and Ktrans (0.775 ± 0.401/min vs. 0.601 ± 0.612/min, p = 0.02) than soft adenomas. Moreover, a significant positive correlation was found between ve and PCC (r = 0.601, p < 0.01). The ve derived using DCE-MRI may have predictive value for consistency of pituitary adenoma.

Longitudinal assessment of bleomycin-induced lung fibrosis by Micro-CT correlates with histological evaluation in mice

BackgroundThe intratracheal instillation of bleomycin in mice induces early damage to alveolar epithelial cells and development of inflammation followed by fibrotic tissue changes and represents the most widely used model of pulmonary fibrosis to investigate human IPF.Histopathology is the gold standard for assessing lung fibrosis in rodents, however it precludes repeated and longitudinal measurements of disease progression and does not provide information on spatial and temporal distribution of tissue damage.Here we investigated the use of the Micro-CT technique to allow the evaluation of disease onset and progression at different time-points in the mouse bleomycin model of lung fibrosis. Micro-CT was throughout coupled with histological analysis for the validation of the imaging results.MethodsIn bleomycin-instilled and control mice, airways and lung morphology changes were assessed and reconstructed at baseline, 7, 14 and 21 days post-treatment based on Micro-CT images. Ashcroft score, percentage of collagen content and percentage of alveolar air area were detected on lung slides processed by histology and subsequently compared with Micro-CT parameters.ResultsExtent (%) of fibrosis measured by Micro-CT correlated with Ashcroft score, the percentage of collagen content and the percentage of alveolar air area (r2 = 0.91; 0.77; 0.94, respectively). Distal airway radius also correlated with the Ashcroft score, the collagen content and alveolar air area percentage (r2 = 0.89; 0.78; 0.98, respectively).ConclusionsMicro-CT data were in good agreement with histological read-outs as micro-CT was able to quantify effectively and non-invasively disease progression longitudinally and to reduce the variability and number of animals used to assess the damage. This suggests that this technique is a powerful tool for understanding experimental pulmonary fibrosis and that its use could translate into a more efficient drug discovery process, also helping to fill the gap between preclinical setting and clinical practice.

Longitudinal assessment of bleomycin-induced lung fibrosis by Micro-CT correlates with histological evaluation in mice

Background: The intratracheal instillation of bleomycin in mice induces early damage to alveolar epithelial cells and development of inflammation followed by fibrotic tissue changes and represents the most widely used model of pulmonary fibrosis to investigate human IPF. Histopathology is the gold standard for assessing lung fibrosis in rodents, however it precludes repeated and longitudinal measurements of disease progression and does not provide information on spatial and temporal distribution of tissue damage. Here we investigated the use of the Micro-CT technique to allow the evaluation of disease onset and progression at different time-points in the mouse bleomycin model of lung fibrosis. Micro-CT was throughout coupled with histological analysis for the validation of the imaging results.&#x0D; Methods: In bleomycin-instilled and control mice, airways and lung morphology changes were assessed and reconstructed at baseline, 7, 14 and 21 days post-treatment based on Micro-CT images. Ashcroft score, percentage of collagen content and percentage of alveolar air area were detected on lung slides processed by histology and subsequently compared with Micro-CT parameters.&#x0D; Results: Extent (%) of fibrosis measured by Micro-CT correlated with Ashcroft score, the percentage of collagen content and the percentage of alveolar air area (r2 = 0.91; 0.77; 0.94, respectively). Distal airway radius also correlated with the Ashcroft score, the collagen content and alveolar air area percentage (r2 = 0.89; 0.78; 0.98, respectively).&#x0D; Conclusions: Micro-CT data were in good agreement with histological read-outs as micro-CT was able to quantify effectively and non-invasively disease progression longitudinally and to reduce the variability and number of animals used to assess the damage. This suggests that this technique is a powerful tool for understanding experimental pulmonary fibrosis and that its use could translate into a more efficient drug discovery process, also helping to fill the gap between preclinical setting and clinical practice.

Assessment of liver fibrosis in primary biliary cholangitis: Comparison between indirect serum markers and fibrosis morphometry

BackgroundThe accuracy of non-invasive methods for the quantification of liver fibrosis in primary biliary cholangitis (PBC) is still debated. AimsTo determine the histo-morphometric measurement of fibrotic tissue and to explore the possible association between indirect markers (APRI, FORNS, FIB-4, and Lok) and morphometry. MethodsRetrospective analysis of medical data from patients with PBC, on whom needle liver biopsy was performed as part of the diagnostic assessment. One section of each biopsy stained with Sirius red was used for calculating the percentage of collagen. Quantitative measure of fibrotic tissue (fibrosis morphometry) was calculated as a percentage of collagen content by digital image analysis. Morphometry results were divided into four groups reflecting Ludwig's staging and compared with values for indirect serum markers. Results50 PBC patients were enrolled (86% females, mean age 57±12.30 years), 19 were Ludwig's stage I (38%), 14 stage II (28%), 12 stage III (24%), and five stage IV (10%). Morphometry results were significantly different among Ludwig stages (p<0.05). No significant differences were found for indirect serum markers. A significant correlation was found between morphometry results and indirect serum markers tested (p<0.05). ConclusionIn our cohort, the histo-morphometric values of fibrotic tissue increased progressively with Ludwig's stages of PBC, while non-invasive markers did not.

VESSEL WALL HETEROGENEITY IS AN IMPORTANT FACTOR IN ABDOMINAL AORTIC ANEURYSM RUPTURE RISK PREDICTION

Current indications for the repair of abdominal aortic aneurysms (AAA) emphasize aortic diameter as a marker for risk of rupture. However, the use of aortic size alone may overlook the role that vessel heterogeneity plays in assessing the risk of rupture. Biomechanics may provide a more nuanced approach to predict the behavior of AAA. The current study was undertaken as a feasibility trial to use pre-operative CT scanning to compute mechanical and fluid mechanical stress profiles on the aortic wall for patients undergoing open AAA repair, and to correlate these stress characteristics with aortic wall histopathology obtained via a sampling grid during aortic reconstruction. One patient with non-ruptured AAA (maximum diameter of 57mm) underwent routine CTA scan examination two weeks prior to the scheduled surgery. The pre-operative mechanical wall stress (MWS) and the time average wall shear stress (TAWSS) fields were predicted by means of finite element analysis (FEA) and computational fluid dynamics (CFD) simulations, respectively. The derived stress maps served as a guide during surgery to collect specimens from patient diseased aorta. Elastin fragmentation and collagen content was evaluated on the collected samples and the correlation between MWS, TAWSS and the underlying histological structure was investigated. The macroscopic MWS and TAWSS were distributed non-uniformly over the wall and large variability of collagen content and elastin fragmentation was observed within the aortic sampling grid.There was a moderate negative correlation between thrombus thickness (TT) and MWS (Pearson’s ρ=-0.43, p=0.03) and between TT and TAWSS (ρ= -0.47, p=0.02). Elastin fragmentation was strongly correlated with the percentage of collagen content in the media (ρ=0.94, p=0.02). The observed regional differences are a consequence of local response of tissue to both mechanical and biological triggers. Therefore, the use of aortic size alone is insufficient to characterize the large degree of heterogeneity present in AAA walls even when considering a single patient. Non- invasive methods to infer local properties would greatly increase the reliability of the pre-operative risk of rupture prediction.

Prediction of Tumor Consistency of Meningiomas using Diffusion Tensor Imaging

Introduction: Skull base meningiomas tend to be intimately attached to cranial nerves, major feeding vessel arteries as well as eloquent brain, thus making their resection quite challenging. In addition, endoscopic skull base approaches limit the natural dexterity available to traditional open surgeons. When deciding between a fully endoscopic approach versus an open approach, surgeons may benefit from knowledge of meningioma consistency (hard vs. soft) to facilitate decision making. Diffusion tensor imaging (DTI) relies on the principles of water diffusion, and we hypothesize that “soft” tumors have greater water diffusion in random directions whereas “hard” tumors have less water diffusion in random directions. In addition, we hypothesize that high content of intercellular collagen is responsible for the hard consistency. The goal of this study is to determine whether DTI can predict tumor consistency as determined by percent collagen contents. Materials and Methods: A total of 42 meningiomas with histopathologic diagnosis of atypical (n = 7; grade II, 7M; age, 47–80 years), anaplastic (n = 2; grade III, 2F; age, 44–56 years), and typical (n = 33;grade I; 8M/25F; age, 27–86 years) meningiomas were included in this study. Subtypes of typical meningiomas include 10 fibroblastic, 7 transitional, 15 meningothelial, and 1 angiomatous. All patients underwent MR studies before surgery on a 3T Siemens scanner. DTI data were acquired using a single shot spin echo EPI sequence with parallel imaging using GRAPPA (acceleration factor = 2). Contrast-enhanced T1-weighted images, FLAIR, and DTI metrics including fractional anisotropy (FA), mean diffusity (MD), linear anisotropy (CL), planar anisotropy (CP), and spherical anisotropy (CS) maps were coregistered and the median values were measured from the enhancing region. After the surgery, the histologic slides from the patients were evaluated for collagen content using sirius red stain. The percentage of collagen content was calculated using the following equation: Collagen content (%) = (collagen area/total tumor area) × 100. DTI metrics and collagen contents were compared between different subtypes. Results: Fibroblastic meningiomas demonstrated significantly higher collagen contents compared with other subtypes. The median FA and CP values were significantly higher in fibroblastic meningiomas compared with other subtypes and atypical meningiomas. The correlation coefficient between FA and collagen contents was 0.43 and between CP and collagen contents was 0.35. Conclusion: DTI may be helpful to predict tumor consistency as determined by collagen contents. This information may influence decision making in skull base surgery for meningiomas.

Age-Related Morphological Changes in Smooth Muscle and Collagen Content in Human Corpus Cavernosum

Aging process has been related to erectile dysfunction (ED) possibly due to morphological changes in corpus cavernosum among many other causes. To evaluate smooth muscle and collagen content in human corpus cavernosum and to correlate it to age. Cadaveric human cavernosal tissue was collected during the period of 1 year. Morphological analysis of a whole corpus cavernosum was performed in tissue sections stained with Masson's trichromic method to differentiate smooth muscle (red) from collagen (blue) content. Analysis was performed with specialized micrographs image analysis software. Pearson's correlation test was used to establish correlation between corpus cavernosum morphology (smooth muscle and collagen content) and age. A total sample of 89 tissues from different male cadavers were analyzed. The average age of the sample was 49.2 ± 19.1 years, with a range between 14 and 90 years. There was a statistically significant inverse correlation between age and the percentage of smooth muscle content (P = 0.012), direct correlation between age and percentage of collagen content (P = 0.019), and inverse correlation between age and the ratio of smooth muscle : collagen content (P = 0.007). Age-related morphological changes in terms of smooth muscle and collagen content are observed in human corpus cavernosum as a possible contributing factor to the development of ED.

Prevention of rupture of atherosclerotic plaque by Candesartan in rabbit model

To evaluate Candesartan therapeutic effect against atherosclerotic plaque rupture and to explore the related mechanisms. Thirty-four New Zealand White male rabbits were randomly divided into three groups: the control group, the model control group and the Candesartan intervention group. The control group rabbits were fed with a normal diet. Rabbits of the latter two groups were fed with a 1% high-cholesterol diet and received a balloon catheter injury respectively one week after the cholesterol feeding. Candesartan (0.5 mgⁱkg⁻¹ⁱd⁻¹) was given to the Candesartan group rabbits 2 days before the performance of the balloon catheter injury. By the end of 12(th) week of the experiment, Russell's viper venom was used for rabbits of both the model control and the Candesartan groups in order to induce rupture of the plaques developed and followed by sacrifice of all the rabbits of the 3 groups. The aortas were removed and fixed for histological evaluation. Immunohistochemistry of MMP-9, macrophage markers and collagen were performed. The protein expression of MMP-9 was determined using Western blot analysis. In the model control group, 7 of 9 rabbits with a total of 12 plaques developed rupture and thrombosis of the plaques after the induction. In contrast, only 2 of 10 rabbits with a total of 3 plaques demonstrated rupture and thrombosis in the Candesartan group (P < 0.05). The control group rabbits did not have plaque rupture and thrombosis. Compared with the model group, both the percentage area of MMP-9 and macrophages in the plaques were significantly decreased in the Candesartan group (12.35% ± 4.28% vs 32.58% ± 9.16%, P < 0.05; 13.87% ± 4.91% vs 23.8% ± 7.45%, P < 0.05). There was an increased percentage of collagen content in total plaques of the Candesartan group (30.27% ± 11.36% vs 4.18% ± 1.28%, P < 0.01). Compared with the model group, the protein expression of MMP-9 was significantly decreased in the Candesartan group (P < 0.01). Candesartan has a preventive value against atherosclerotic plaque rupture in hypercholesterolemic rabbits, likely through its reduction of MMP-9 expression, inhibition of macrophage accumulation and increase of collagen content within the plaques.

Abstract 519: Pathogenic Mechanisms of Il-17 In Atherogenesis - In Vivo and In Vitro Studies

Atherosclerotic plaque typically contains infiltrates of activated macrophages and T cells. In human carotid artery plaques, we previously showed the presence of IL-17 producing T cells (Th17) and IL-23. This study investigated possible pathogenic mechanisms of IL-17 on atherogenesis in ApoE −/− mice and its effects on vascular cells in vitro. 25 female ApoE −/− mice fed a normal diet were treated with a specific blocking antibody against IL-17 for 12 weeks (100 μg intraperitoneally once per week) compared to unteated mice (reveiving a control IgG). In vitro endothelial cells and RAW cells were either treated with IL-17 1000ng/ml alone as well as in addition to TNF-α or LPS. SMCs were incubated with IL-17 or additional IFN-γ to induce apoptosis. IL-17 mAb treatment resulted in a &gt; 60% reduction of plaque volume and fractional luminal stenosis in the aortic root. IL-17 mAb treated mice showed higher percentage of collagen content in the lesion, especially in the area of the fibrous cap. In addition, the amount of SMCs was also significantly higher in the area of the fibrous cap in IL-17 mAb treated mice. RT-PCR results showed signifcantly reduced caspase 3 expression in IL-17 mAb treated mice. The possible stabilizing effects in IL-17 mAb treated mice was in line with findings that IL-17 was found to induce apoptosis in SMCs in vitro. In vitro studies further showed that IL-17 itself induced pro-inflammatory changes in macrophages as well as endothelial cells and also acted synergistically with TNF-α or LPS. Functional blockade of Th1 cytokine IL-17 reduces atherosclerotic plaque, stabilizes the atherosclerotic lesion by higher amount of SMC and collagen content in the area of the fibrous cap as well as reduced apoptosis in the lesion. Inflammatory changes in ECs, Ms and SMCs leading to cell death and increased immune cell infiltration may represent possible pathogenic mechanisms of IL-17 in atherogenesis.

Pituitary Macroadenomas: Preoperative Evaluation of Consistency with Diffusion-weighted MR Imaging—Initial Experience

To prospectively evaluate use of diffusion-weighted (DW) magnetic resonance (MR) images and apparent diffusion coefficient (ADC) maps for determination of the consistency of macroadenomas. The study protocol was approved by the institutional ethics committee, and informed consent was obtained from all patients. Twenty-two patients with pituitary macroadenoma (10 men, 12 women; mean age, 54 years +/- 17.09 [standard deviation]; range, 21-75 years) were examined. All patients underwent MR examination, which included T1-weighted spin-echo and T2-weighted turbo spin-echo DW imaging with ADC mapping and contrast material-enhanced T1-weighted spin-echo imaging. Regions of interest (ROIs) were drawn in the macroadenomas and in normal white matter on DW images, ADC maps, and conventional MR images. Consistency of macroadenomas was evaluated at surgery and was classified as soft, intermediate, or hard. Histologic examination was performed on surgical specimens of macroadenomas. Mean ADC values, signal intensity (SI) ratios of tumor to white matter within ROIs on conventional and DW MR images, and degree of enhancement were compared with tumor consistency and with percentage of collagen content at histologic examination by using analysis of variance for linear trend. The mean value of ADC in the soft group was (0.663 +/- 0.109) x 10(-3) mm(2)/sec; in the intermediate group, (0.842 +/- 0.081) x 10(-3) mm(2)/sec; and in the hard group, (1.363 +/- 0.259) x 10(-3) mm(2)/sec. Statistical analysis revealed a significant correlation between tumor consistency and ADC values, DW image SI ratios, T2-weighted image SI ratios, and percentage of collagen content (P < .001, analysis of variance). No other statistically significant correlations were found. Findings in this study suggest that DW MR images with ADC maps can provide information about the consistency of macroadenomas.

Technical Considerations of Transsphenoidal Removal of Fibrous Pituitary Adenomas and Evaluation of Collagen Content and Subtype in the Adenomas.

Pituitary adenomas are usually soft, but 5-13.5% are fibrous adenomas which are difficult to remove. Magnetic resonance (MR) imaging and operative findings were evaluated in eight patients (12.1%) with fibrous pituitary adenoma among 66 patients. Tumor specimens were examined histologically and immunohistochemically for collagen content and subtypes. Seven patients had clinically inactive non-functioning pituitary adenomas and one patient growth hormone-secreting adenoma. All patients underwent transsphenoidal surgery. Four cases were giant adenomas with suprasellar extension of more than 2 cm. T1- and T2-weighted MR imaging showed the tumors as nearly isointense to the surrounding brain, except in one case where the tumor was high intense on T2-weighted MR imaging. All tumors required piecemeal resection using a micro-dissector and tumor forceps. Four tumors of maximum size more than 3 cm needed a second operation. The interface between the thinned normal pituitary gland and fibrous adenoma was intended to identify at the anterior-superior portion in recent four cases, which was helpful to remove the tumors and preserve pituitary functions. Histological examination revealed prominent deposition of collagen in the perivascular area. The percentage of collagen content in fibrous adenomas was more than 5% and significantly higher than that in soft adenomas and normal pituitary glands. Immunohistochemical examination showed positive staining for collagen types I and III in the fibrous adenomas, but only for type V collagen in the normal pituitary glands. Large fibrous adenomas can be resected by transsphenoidal surgery which may require two-stage operations. Identification of the interface between the normal pituitary gland and adenoma is helpful to remove fibrous adenomas and to preserve pituitary functions. We propose that firm adenomas containing more than 5% collagen are "fibrous" adenomas.

MRI prediction of fibrous pituitary adenomas.

The transsphenoidal approach is a less invasive and safer procedure for removing pituitary adenomas. However, this procedure becomes extremely difficult when the tumour consistency is fibrous as encountered in about 10% of pituitary adenomas. In this study, we investigated predicting factors of tumour consistency in magnetic resonance images (MRIs). MRIs of two groups, twenty-one soft and five firm (fibrous) adenomas, were retrospectively evaluated and compared in respect of tumour consistency. To compare the two groups objectively, tumour densities on MRI films and percentage of collagen content on operative specimens were expressed as numerical data using NIH-image. The relationships between collagen content and T1-weighted images, T2-weighted images, grade of enhancement effect, and heterogeneity of enhancement were investigated. Signal intensities on T1-weighted images were not correlated with tumour consistency, whereas those on T2-weighted images were significantly correlated with the percentage of collagen content. Adenomas, showing lower signal intensities on T2-weighted images, contained more collagen. On enhanced images, homogeneously enhanced adenomas tended to include more collagen, even though the grade of enhancement effect showed only weak correlation with the tumour hardness. MRIs give us useful information on tumour consistency. Adenomas may be firm and fibrous if they show low signal intensities on T2-weighted images and homogeneous enhancement. To remove such tumours, a long sized and small-calibred ultrasonic aspirators applicable to transsphenoidal approach must be prepared and multistaged operations may be more than likely needed.

Changes in collagen composition and cross-links in bone and skin of osteoporotic postmenopausal women treated with percutaneous estradiol implants

To determine the effects of percutaneous estradiol (E2) implants on the collagen composition and maturity in the bone and skin of osteoporotic postmenopausal women.Sixteen postmenopausal women with low bone mineral density were treated for 1 year with 75-mg E2 implants. Iliac crest bone and skin biopsies were analyzed for collagen content and collagen cross-links before treatment and at 1 year. Dual energy x-ray absorptiometry of the lumbar spine and proximal femur was also performed before and after 1 year of therapy.The cortical bone showed a significant increase in the mature cross-links of both hydroxylysylpyridinoline (P < .01) and lysylpyridinoline (P < .01), with a significant reduction in the percentage of collagen (P < .001). The pattern was similar in trabecular bone, with lysylpyridinoline increasing significantly (P < .05). The skin exhibited a significant reduction in the immature cross-link hydroxylysinonorleucine (P < .01), but no significant change in the percentage of collagen content or the mature cross-link histidinohydroxylysinonorleucine. The median increases in bone density were 11.5% at the spine and 4.34% at the total hip. The median post-treatment serum E2 level was 639 pmol/L.Bone mineral density increased at all the sites measured in the spine and proximal hip. The quality of the collagen within the transiliac biopsies had matured in that the concentration of the mature collagen cross-links had increased. These findings support a reduction in the turnover of bone collagen following estrogen replacement therapy. More important, the formation of a more mature collagen fiber should help to reduce the risk of future bone fracture.