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Stability, tissue metabolism, tissue distribution, and blood partition of DA-1131, a new carbapenem.

The stability of DA-1131 after incubation in various pH solutions, human plasma, human urine, human gastric juice, rat liver homogenates and rat whole blood, the disappearance of DA-1131 after incubation in the 9000g supernatant fraction of various rat tissue homogenates in the presence of NADPH, the tissue distribution of DA-1131 after intravenous (i.v.) administration of DA-1131, 50 mg/kg, to rats, and the blood partition of DA-1131 between plasma and blood cells from rabbit blood were studied. DA-1131 was unstable when incubated in various pH solutions, especially at low and high pHs at the DA-1131 concentration of 10 micro g/ml; the degradation half-lives of DA-1131 were 0.260, 1.23, 2.20, 7.16, 14.2, 10.5, 31.3, 21.3, 0.262, 0.241, and 1.45 hr for pH solutions of 1-11, respectively. DA-1131 was also unstable after incubation in human plasma, rat liver homogenates, and human gastric juice. However, DA-1131 seemed to be sable in human plasma for up to 12 hr storage at -20 degrees C. The spleen, kidney, liver, lung, mesentery, and stomach homogenates from rats showed metabolic activity to DA-1131. The tissue-to-plasma ratios of DA-1131 were lower than unity in all tissues studied except kidney when each tissue was collected at 30 min after i.v. administration of DA-1131 to rats. The tissue-to-plasma ratios of DA-1131 were lower than unity in all tissues studied except kidney when each tissue was collected at 30 min after i.v. administration of DA-1131 to rats. The plasma-to-blood cell concentration ratios of DA-1131 were independent of DA-1131 blood concentrations when the whole blood was incubated up to 120 min; the mean values were 5.56 +/- 1.47, 5.80 +/- 2.19, and 4.61 +/- 1.82 at DA-1131 blood concentrations of 2, 10, and 20 microgram/ml, respectively, rabbits A-C. There was also considerable in vivo and in vitro blood storage effect in the plasma concentration of DA-1131 in rabbits.

Animals↗

Formation of granulation tissue in subcutaneously implanted sponges in rats. A comparison between granulation tissue developed in viscose cellulose sponges (Visella) and in polyvinyl alcohol sponges (Ivalon).

A comparison was made between the granulation tissue formation in two different synthetic sponge types. Visella and Ivalon, of different sizes. The granulation tissue formed in the two sponge types did not differ qualitatively, and had the character of wound tissue and inflammatory tissue in man. The rate of tissue formation in the Visella sponges was faster and the tissue was more homogenous than in the Ivalon sponges. Fourteen-day-old Visella implants of either size contained more granulation tissue than Ivalon sponges, probably owing to the smaller pore size of the former material. This may also account for the more frequent occurrence of giant cells in the Visella implants. In contrast to the Visella sponges, the trabeculae of the Ivalon polymer showed calcification and positive staining properties with histological staining procedures, and deformation was frequent among the Ivalon implants. Thin sponges of either type closed in about 21 days, thick ones after about 42 days of implantation. Calculated per 2 cm3 of implant, thin sponges produced more tissue after 14 days of implantation than thick noes. It is concluded that the Visella sponge type is best suitable for this experimental model of inflammation.

Animals↗

[Expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in joint tissues of rapidly destructive coxarthropathy (RDC), analyzed by immunohistochemical study].

OBJECTIVE: Rapidly destructive coxarthropathy (RDC) is characterized by rapid destruction of hip joints, but its pathogenetic mechanism is still obscure. Matrix metalloproteinases (MMPs) are possibly one of the candidates concerning with this mechanism. We attempted histochemical investigation to demonstrate MMPs and tissue inhibitor of metalloproteinases (TIMPs) in joint tissues obtained from RDC patients to clarify their roles in the destruction mechanism. MATERIALS AND METHODS: Joint tissues including synovia and cartilage-bone tissues were obtained from RDC patients at total hip replacement (THR). After fixation with 4% paraformaldehyde, cartilage-bone tissues were partly decalcified. We performed histochemical study for paraffin sections of these tissues by using avidin-biotin method. Antibodies used in this study were monoclonal antibodies to MMP-1, MMP-2, MMP-7, MMP-8, MMP-9, TIMP-1, TIMP-2 and polyclonal antibody to MMP-3. RESULTS: Histological feature of RDC was severe destruction of cartilage and bone by invasion of non-specific granulation tissues composed of many small vessels, macrophages and fibroblastic cells. At the same time, RDC showed apparently fewer lymphocytic cells in these granulation tissues compare with rheumatoid arthritis. MMP-2 and MMP-9 were expressed most demonstrably in synovia and destructive regions of femoral heads, especially in osteoclasts, macrophages, and fibroblastic cells, while MMP-1, MMP-3, were slightly expressed only in the superficial layer of synovia in limited cases. MMP-8, usually contained in neutrophils, was not present in RDC. On the other hand TIMP-1 and TIMP-2 were presented throughout the synovia and destructive regions of femoral heads including fibroblastic cells, macrophages, osteoblasts and osteocytes. CONCLUSION: Immunohistochemical study revealed obvious presence of MMP-2 and MMP-9 in synovia and destructive regions of femoral heads in RDC. Those evidence suggest that MMP-2 and MMP-9 share very important role in the destructive mechanism of RDC, possibly under imbalance between TIMPs.

Aged↗

Adipose tissue-derived mesenchymal stem cell yield and growth characteristics are affected by the tissue-harvesting procedure.

BACKGROUND: Adipose tissue contains a stromal vascular fraction that can be easily isolated and provides a rich source of adipose tissue-derived mesenchymal stem cells (ASC). These ASC are a potential source of cells for tissue engineering. We studied whether the yield and growth characteristics of ASC were affected by the type of surgical procedure used for adipose tissue harvesting, i.e. resection, tumescent liposuction and ultrasound-assisted liposuction. METHODS: Frequencies of ASC in the stromal vascular fraction were assessed in limiting dilution assays. The phenotypical marker profile of ASC was determined, using flow cytometry, and growth kinetics were investigated in culture. ASC were cultured under chondrogenic and osteogenic conditions to confirm their differentiation potential. RESULTS: The number of viable cells in the stromal vascular fraction was affected by neither the type of surgical procedure nor the anatomical site of the body from where the adipose tissue was harvested. After all three surgical procedures, cultured ASC did express a CD34+ CD31- CD105+ CD166+ CD45- CD90+ ASC phenotype. However, ultrasound-assisted liposuction resulted in a lower frequency of proliferating ASC, as well as a longer population doubling time of ASC, compared with resection. ASC demonstrated chondrogenic and osteogenic differentiation potential. DISCUSSION: We conclude that yield and growth characteristics of ASC are affected by the type of surgical procedure used for adipose tissue harvesting. Resection and tumescent liposuction seem to be preferable above ultrasound-assisted liposuction for tissue-engineering purposes.

Adipocytes↗

Higher production of IL-8 in visceral vs. subcutaneous adipose tissue. Implication of nonadipose cells in adipose tissue.

IL-8 is released from human adipose tissue. Circulating IL-8 is increased in obese compared with lean subjects and is associated with measures of insulin resistance, development of atherosclerosis, and cardiovascular disease. We studied 1) the production and release of IL-8 in vitro from paired samples of subcutaneous (SAT) and visceral (VAT) adipose tissue and 2) the production of IL-8 from whole adipose tissue, isolated adipocytes, and nonfat cells of adipose tissue. IL-8 release from VAT was fourfold higher than from SAT (P < 0.05), and IL-8 mRNA was twofold higher in VAT compared with SAT (P < 0.01). Dexamethasone (50 nM) attenuated IL-8 production by 50% (P < 0.05), and IL-1beta (2 microg/l) increased IL-8 production up to 15-fold (P < 0.001). IL-8 release from whole SAT explants correlated with body mass index (BMI; r = 0.78; P < 0.001), as did IL-8 release from nonfat cells (r = 0.79; P < 0.001). However, no correlation was found between IL-8 release from the fraction of isolated adipocytes and BMI (r = 0.01). In conclusion, we demonstrated an increased release of IL-8 from VAT compared with SAT. Furthermore, our data suggest that the observed elevation in circulating levels of IL-8 in obese subjects is due primarily to the release of IL-8 from nonfat cells from adipose tissue. The high levels of IL-8 release from human adipose tissue and accumulation of this tissue in obese subjects may account for some of the increase in circulating IL-8 observed in obesity.

Adipocytes↗

A comparison of 2 root coverage techniques: guided tissue regeneration with a bioabsorbable matrix style membrane versus a connective tissue graft combined with a coronally positioned pedicle graft without vertical incisions. results of a series of consecutive cases.

Root coverage procedures have become an important part of periodontal therapy. The purpose of this study was to compare 2 techniques, 1) guided tissue regeneration (GTR) with a bioabsorbable polylactic acid softened with citric acid ester membrane and 2) the connective tissue graft combined with a coronally positioned pedicle graft without vertical incisions. The GTR procedure produced a mean root coverage of 92.3% and the connective tissue graft combined with a coronally positioned pedicle graft, 95.0%. This difference was not statistically significant. Both procedures produced similar reductions in recession depth, recession width, and probing depth. The connective tissue graft combined with a coronally positioned pedicle graft resulted in a greater increase in the amount of keratinized tissue. Based on this study, both procedures can result in statistically similar amounts of mean root coverage, but the results are not identical. In most cases, the connective tissue with coronally positioned pedicle graft produced a more bulky result than guided tissue regeneration. Therefore, the procedures are not interchangeable.

Adult↗

Secretion of Osteopontin by macrophages and its accumulation at tissue surfaces during wound healing in mineralized tissues: a potential requirement for macrophage adhesion and phagocytosis.

Osteopontin (OPN), a noncollagenous, extracellular matrix sialoprotein found at relatively high levels in both normal and pathological mineralized tissues, is expressed by tissue-specific cells in bone, calcified cartilage, and teeth. On the other hand, a hallmark of OPN expression in pathologically mineralizing tissue, and in other soft tissues experiencing a more generalized type of necrotic injury, is the production of OPN by macrophages at the lesion site. In the present study, we have localized OPN and other noncollagenous proteins by ultrastructural colloidal-gold immunocytochemistry using a rat model in which mineralized tissue defects are surgically created in mandibular bone and teeth. The healing response was examined by immunocytochemistry and transmission electron microscopy at 10 min, 3 days and 7 days post-surgery using antibodies against OPN, bone sialoprotein, osteocalcin, bone acidic glycoprotein-75, fibronectin, and amelogenin. Whereas most of these proteins were characteristically distributed within their respective extracellular matrices as described previously, OPN was additionally observed to accumulate as a lamina limitans at surgically exposed bone and tooth surfaces, as well as at the surface of particulate, mineralized tissue debris. Intracellular labeling of the Golgi apparatus and secretory granules of macrophages at the lesion site demonstrated that OPN production by macrophages was a prominent secretory event of the inflammatory response during wound healing in mineralized tissues. Pseudopodal and lamellipodal cytoplasmic extensions of macrophages were observed in direct contact with the OPN-containing lamina limitans at these surfaces. Particulate, calcified debris internalized by macrophages also displayed a prominent surface "coating" of OPN. In conclusion, our interpretation of the present data is that OPN secreted by macrophages may serve as a macrophage adhesion protein, and where concentrated at the surface of small particulate, mineralized tissue debris, may act as an opsonin, thereby facilitating cell adhesion and phagocytosis by macrophages, a process likely mediated by integrin-binding, signal transduction, and cytoskeletal restructuring.

Amelogenin↗

Adjuvant chemotherapy for localised resectable soft tissue sarcoma in adults. Sarcoma Meta-analysis Collaboration (SMAC).

BACKGROUND: Individually, randomised trilas have not shown conclusively whether adjuvant chemotherapy benefits adult patients with localised resectable soft-tissue sarcoma. OBJECTIVES: Adjuvant chemotherapy aims to lessen the recurrence of cancer after surgery with or without radiotherapy. The objective of this review was to assess the effects of adjuvant chemotherapy in adults with resectable soft tissue sarcoma after such local treatment. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, UKCCCR Register of Cancer Trials, Physicians Data Query, EMBASE, MEDLINE and CancerLit. SELECTION CRITERIA: Randomised trials of adjuvant chemotherapy after local treatment in adults with localised resectable soft tissue sarcoma were included. Only trials in which accrual was completed by December 1992 were included. DATA COLLECTION AND ANALYSIS: Individual patient data were obtained. Accuracy of data and quality of randomisation and follow-up of trials was assessed. MAIN RESULTS: Fourteen trials of doxorubicin-based adjuvant chemotherapy involving 1568 patients were included. Median follow-up was 9.4 years. For local recurrence-free interval the hazard ratio with chemotherapy was 0.73 (95% Confidence Interval 0.56-0.94). For distant recurrence-free interval it was 0. 70 (95% CI 0.57-0.85). For overall recurrence-free survival it was 0. 75 (95% CI 0.64-0.87). These correspond to significant absolute benefits of 6-10% at 10 years. For overall survival the hazard ratio of 0.89 (95% CI 0.76-1.03) was not significant but potentially represents an absolute benefit of 4% (95% CI -1 to 9) at 10 years. There was no consistent evidence of a difference in effect according to age, sex, stage, site, grade, histology, extent of resection, tumour size or exposure to radiotherapy. However, the strongest evidence of a beneficial effect on survival was shown in patients with sarcoma of the extremities. REVIEWER'S CONCLUSIONS: Doxorubicin-based adjuvant chemotherapy appears to significantly improve time to local and distant recurrence and overall recurrence-free survival in adults with localised resectable soft tissue sarcoma. There is some evidence of a trend towards improved overall survival.

Adult↗

Three-dimensional method for comparing in vivo interventional MR images of thermally ablated tissue with tissue response.

PURPOSE: To investigate the ability of magnetic resonance (MR) to monitor radio-frequency (RF) ablation treatments by comparing MR images of thermal lesions to histologically assayed cellular damage. We developed a new methodology using three-dimensional registration for making spatial correlations. MATERIALS AND METHODS: A low-field, open MRI system was used to guide an ablation probe into rabbit thigh muscle and acquire MR volumes after ablation. After fixation, we sliced and photographed the tissue at 3-mm intervals, using a specially designed apparatus, to obtain a volume of tissue images. Histologic samples were digitized using a video microscopy system. For our three-dimensional registration method, we used the tissue images as the reference, and registered histology and MR images to them using two different computer alignment steps. First, the MR volume was aligned to the volume of tissue images by registering needle fiducials placed near the tissue of interest. Second, we registered the histology images with the tissue images using a two-dimensional warping technique that aligned internal features and the outside boundary of histology and tissue images. RESULTS: The MR and histology images were very well aligned, and registration accuracy, determined from displacement of needle fiducials, was 1.32 +/- 0.39 mm (mean +/- SD), which compared favorably to the MR voxel dimensions (0.70 mm in-plane and 3.0 mm thick). A preliminary comparison of MR and tissue response showed that the region inside the elliptical hyperintense rim in MR closely corresponds to the region of necrosis as established by histology, with a mean absolute distance between MR and histology boundaries of 1.17 mm, slightly smaller than the mean registration error. The MR region slightly overestimated the region of necrosis, with a mean signed distance between boundaries of 0.85 mm. CONCLUSION: Our results suggest that our methodology can be used to achieve three-dimensional registration of histology and in vivo MR images. In MR lesion images, the inner border of the hyperintense region corresponds to the border of irreversible cell damage. This is good evidence that during RF ablation treatments, iMRI lesion images can be used for real-time feedback.

Animals↗

Quantitative measurement of porphyrins in biological tissues and evaluation of tissue porphyrins during toxicant exposures.

Porphyrins are formed in most eukaryotic tissues as intermediates in the biosynthesis of heme. Assessment of changes in tissue porphyrin levels occurring in response to the actions of various drugs or toxicants is potentially useful in the evaluation of chemical exposures and effects. The present paper describes a rapid and sensitive method for the extraction and quantitation of porphyrins in biological tissues which overcomes difficulties encountered in previously described methods, particularly the loss of porphyrins during extraction and interference of porphyrin quantitation by coeluting fluorescent tissue constituents. In this procedure 8- through 2-carboxyl porphyrins are quantitatively extracted from tissue homogenates using HCl and methanol and are subsequently separated from potentially interfering contaminants by sequential methanol/phosphate elution on a C-18 preparatory column. Porphyrins are then separated and measured by reversed-phase high-performance liquid chromatography and spectrofluorometric techniques. Recovery of tissue porphyrins using this method is close to 100% with an intraassay variability of less than 10%. We have employed this procedure to measure liver and kidney porphyrin concentrations in male Fischer rats and to define the distinctive changes in tissue porphyrin patterns associated with treatment with the hepatic and renal porphyrinogenic chemicals, allylisopropylacetamide, and methyl mercury hydroxide, respectively. This method is applicable to the measurement of tissue porphyrin changes resulting from drug or toxicant exposures in clinical, experimental or environmental assessments.

Allylisopropylacetamide↗

Elevation of tissue PO2 with improvement of tissue perfusion by topically applied CO2.

Local absorption of CO2 was examined, by tissue gas analysis with medical mass spectrometry, in rabbits placed in a bath. The results obtained clearly showed that (1) Elevation of subcutaneous tissue PO2 was followed by elevation of PCO2 in the subcutaneous tissue. (2) Local absorption of CO2 through skin was confirmed by elevation of the levels of subcutaneous PO2 and PCO2 at the site exposed to CO2. (3) Tissue perfusion during the CO2 bath was moderately higher than that observed with tap water bathing. The mechanism of oxygen release into the tissue by CO2 bathing is thought to involve increased [H+] and PCO2 in the red blood cells, which shifts the hemoglobin dissociation curve to the right, thus facilitating oxygen release at the tissue level. There is, therefore a good possibility, that the improved tissue perfusion together with the increased oxygen in the tissue will favourably affect wound healing and chronic degenerative disorders, thus facilitating rehabilitation.

Animals↗

Bone sialoprotein in developing porcine dental tissues: cellular expression and comparison of tissue localization with osteopontin and osteonectin.

Bone sialoprotein (BSP) is a highly sulphated and glycosylated phosphoprotein that is a major constituent of bone and other mineralized connective tissues. Although BSP can mediate cell attachment through an RGD sequence and binds selectively to hydroxyapatite, its precise function in mineralized tissues is unknown. To provide insights into its possible function, affinity-purified polyclonal antibodies directed against porcine BSP were used to demonstrate the histological distribution of this protein in developing porcine mandibular alveolar bone and the associated tooth tissues from 35- and 50-day fetuses. In addition, a porcine cRNA probe was used to determine the cellular expression of BSP in the same tissues by in situ hybridization. Immunoreactivity to BSP protein was restricted to the cells and matrix of the mineralized tissues of alveolar bone and dentine. In dentine, BSP was localized to the odontoblasts and their processes and to the peritubular dentine. In the alveolar bone, immunoreactivity for BSP was evident in osteoblastic cells and osteocytes and in the bone matrix; the older bone stained more strongly than newly formed bone. In addition, BSP appeared to be concentrated in the reversal lines of the rapidly remodelling bone. The distribution of BSP in these tissues revealed distinct differences when compared to osteopontin and SPARC/osteonectin, which are also prominent non-collagenous proteins of mineralized tissues. Most notable was the localization of osteopontin and especially osteonectin in non-mineralizing tissues. The immunoreactivity of osteoblasts and osteocytes for BSP in bone was consistent with the high levels of BSP mRNA revealed by in situ hybridization. However, much lower levels of hybridization were evident in the odontoblasts of developing mandibular molars. These studies demonstrate that BSP is expressed during the early formation of dentine and alveolar bone and that the protein accumulates in the peritubular dentine and bone matrix.

Alveolar Process↗

Lean R value for DXA two-component soft-tissue model: influence of age and tissue or organ type.

Dual-energy X-ray absorptiometry (DXA) is an important new body composition method that is based on tissue attenuation of two main photon energies. When the two photon energies pass through tissue, attenuation at the lower energy compared with that at the higher energy can expressed as a ratio (R), which is used for tissue component identification. We tested whether: (1) the R value of lean tissue is related to age, and (2) the R value of lean tissue differs between soft tissue locations. Elemental content of various tissues from the literature was used. Results show that lean R values for 40 keV and 70 keV are independent of age and tissue type.

Absorptiometry, Photon↗

Charitable State-Controlled Foundation Human Tissue and Cell Research: Ethic and Legal Aspects in the Supply of Surgically Removed Human Tissue For Research in the Academic and Commercial Sector in Germany.

Tissue engineering using human cells and tissue has one of the greatest scientific and economical potential in the coming years. There are public concerns during the ongoing discussion about future trends in life sciences and if ethic boundaries might be respected sufficiently in the course of striving for industrial profit and scientific knowledge. Until now, the legal situation of using human tissue material for research is not clear. Accordingly, transparency of action and patients' information are a central component when handling patient material inside and outside of the patient-specific treatment. Whereas in the field of therapeutic use of tissue (e.g. transplantation) there is an emergency situation by the shortage of organs with the risk of the premature death of the potential recipient, this cannot be claimed for tissue donation for research. The basis of every surgical operation is the treatment contract, which places the doctor under obligation to the careful exercise of medical treatment containing the patient's informed consent. This contract only covers the treatment that is intended to cure the patient and the medical measures that are necessary therefor. The further scientific use of body-substances, which are discarded after an operation, are not included. Therefore a personal and independent written enlightenment of the patient and a declaration of informed consent is necessary. Examples of guidelines for tissue supply, Patients information and consent were worked out by theologists, lawyers, scientists and physicians reflecting their practical experience in transplant surgery and liver cell research. As a consequence to cover the ethical and legal aspect of tissue donation in Germany a charitable state-controlled foundation Human Tissue and Cell Research (HTCR) was introduced and established.

Journal Article↗

The promoter of the mouse tissue transglutaminase gene directs tissue-specific, retinoid-regulated and apoptosis-linked expression.

Tissue transglutaminase is a multifunctional enzyme that accumulates to high levels in cells undergoing apoptosis. Retinoids act as an acute and direct regulator of tissue transglutaminase gene transcription. The studies reported here were carried out to elucidate the molecular mechanisms involved in the regulation of tissue transglutaminase expression. We have isolated and characterized the mouse tissue transglutaminase gene promoter and 3.8 kb of 5'-flanking DNA. A large fragment of the promoter that includes both the core promoter and 3.8 kb of 5'-flanking DNA shows retinoid-dependent transcriptional activity when stably transfected into HeLa cells. In these stably transfected HeLa cells both the endogenous tissue transglutaminase gene and transfected mouse tissue transglutaminase promoter are activated by all-trans retinoic acid and by retinoic acid receptor (RAR)-specific and retinoid X receptor (RXR)-specific retinoids. In embryos made transgenic with a transglutaminase promoter-beta-galactosidase reporter gene, the transgene shows specific patterns of expression during limb development. The transglutaminase transgene is expressed in cartilage, the cells of the apical ectodermal ridge, and in regions of apoptotic cell death of the interdigital mesenchyme. It appears that cis-acting elements responsible for the complex retinoid regulation, tissue- and apoptosis-specific expression are embedded within the proximal 3.8 kb of DNA flanking the 5'-end of the mouse tissue transglutaminase gene.

Journal Article↗

Soft tissue to hard tissue advancement ratios for mandibular elongation using distraction osteogenesis in children.

Distraction osteogenesis is extensively used for the elongation of hypoplastic mandibles in children, yet the soft tissue profile response to this is not well understood. The pre- and posttreatment lateral cephalometric radiographs of 27 pediatric patients who underwent bilateral mandibular elongation using distraction osteogenesis were analyzed retrospectively to correlate horizontal soft tissue advancement with horizontal underlying bone advancement at B point and pogonion. Horizontal advancement (in millimeters) of bone and overlying soft tissue at these points was collected from the radiographs of each patient, and linear regression analysis was performed to determine the relationship of hard to soft tissue horizontal advancement at these points. A 1:0.90 mean ratio of bone to soft tissue advancement was observed at B point/labiomental sulcus and at pogonion/soft tissue pogonion (linear regression analysis demonstrated slopes [beta1 values] of 0.94 and 0.92, respectively). These ratios were consistent throughout the sample population and are highly predictive of the soft tissue response that can be anticipated. Magnitude of advancement, age, and sex of the patient had no effect on these ratios in our population. This study assists with our understanding of the soft tissue response that accompanies bony elongation during distraction osteogenesis which will allow us to more effectively treatment plan the orthodontic and surgical intervention that will optimize the patients' functional and esthetic outcome.

Adolescent↗

Specific soft tissue mobilization in the management of soft tissue dysfunction.

SUMMARY. Following injury, the ability of soft tissue to tolerate the demands of functional loading decreases. A major part of the management of soft tissue dysfunction lies in promoting soft tissue adaptation to restore the tissue's ability to cope with functional loading. Specific soft tissue mobilization (SSTM) uses specific, graded and progressive application of force by the use of physiological, accessory or combined techniques either to promote collagen synthesis, orientation and bonding in the early stages of the healing process, or to promote changes in the viscoelastic response of the tissue in the later stages of healing. SSTM should be applied in combination with rehabilitation regimes to restore the kinetic control of the tissue. The principles of SSTM are reviewed with regard to the general principles of treating soft tissue dysfunction and areas identified for further research into this field. Copyright 1998 Harcourt Publishers Ltd.

Journal Article↗

Anticoagulant actions of tissue factor pathway inhibitor on tissue-factor-dependent plasma coagulation.

The initiation and propagation of in vivo coagulation are thought to be catalyzed by factor VIIa-tissue factor (an activator of factor X and factor IX) and factor IXa-factor VIIIa (an activator of factor IX), respectively. The enzymatic activity of factor VIIa-tissue factor is abrogated by tissue factor pathway inhibitor (TFPI), which anchors a quaternary complex consisting of equimolar TFPI, factor Xa, factor VIIa, and tissue factor in which both factor Xa and factor VIIa are inactive. This study compared the anticoagulant effectiveness of TFPI (which also inactivates prothrombinase-bound factor Xa), hirudin (which inactivates thrombin), and heparin (which catalyzes the inactivation of factor Xa and thrombin by antithrombin III). Factor X and prothrombin activation were initiated by adding 5 pM r-tissue factor in a suspension of coagulant phospholipids and CaCl2 to defibrinated plasma. Compared on the basis of their ability to delay the initiation of and inhibit factor X and prothrombin activation, the anticoagulant effectiveness of 0.5 nM TFPI was greater than those of 10 nM hirudin and approximately 100 nM (0.1 unit/mL) heparin. However, a 100-fold molar excess of TFPI over tissue factor could not abrogate factor X and prothrombin activation in plasma. These results suggest that propagation of tissue-factor dependent coagulation is catalyzed by factor IXa-factor VIIIa, which unlike factor VIIa-tissue factor, is not inactivated by TFPI.

Animals↗