Biomedical subjects

S T Chou

Publications and source records attributed to S T Chou.

At least 19 recordsLinked to original sources

PubMed2001

Studies on the antioxidative activities of Hsian-tsao (Mesona procumbens Hemsl) leaf gum.

This study aimed at evaluating the antioxidative activity of crude hsian-tsao leaf gum extracted by sodium bicarbonate solutions and precipitated by 70% ethanol. The antioxidative activities, including the radical-scavenging effects, Fe(2+)-chelating ability, and reducing power as well as the inhibition of FeSO(4)-H(2)O(2)-induced malondialdehyde formation in rat tissue homogenate were studied in vitro. It was found that the antioxidative effect provided by hsian-tsao leaf gum was strongly concentration dependent. In general, the antioxidative activity increased with increasing gum concentration, to a certain extent, and then leveled off with further increase in gum concentration. A concentrtaion-dependent kinetics for the rate of change in antioxidative activity was proposed. The antioxidative activity constant (k) and the half-inhibition concentration (IC(50)) for each antioxidative reaction studied were calculated. From a comparison of the IC(50) values for different antioxidative reactions, it seemed that hsian-tsao leaf gum was more effective in scavenging superoxide radicals than chelating Fe(2+) or scavenging alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) radicals. As compared to the commercial antioxidants, hsian-tsao leaf gum showed less scavenging effect on the DPPH radical and reducing power but better superoxide radical-scavenging effect and Fe(2+)-chelating ability than alpha-tocopherol and BHT.

Animals↗

PubMed2000

Effect of age and sex on plasma total homocysteine in Taiwanese subjects.

Plasma total homocysteine (tHcy) is now established as a clinical risk factor for coronary artery disease, as well as for other arterial and venous occlusive diseases. Therefore, we measured the plasma tHcy concentrations in 385 healthy Chinese subjects in Taiwan and in 40 patients with occluded coronary artery disease or maintenance hemodialysis. The plasma tHcy levels in Taiwanese male and female volunteers were found to increase gradually with age (age group: 20-29, 30-39, 40-49, 50-59, and >60; mean +/- SD 8.22 +/- 2.00, 8.51 +/- 2.67, 8.87 +/- 2.22, 11.41 +/- 2.50 and 13.28 +/- 2.31 microM for male volunteers and 6.49 +/- 1.75, 7.15 +/- 1.20, 7.40 +/- 1.30, 9.57 +/- 3.01 and 10.95 +/- 2.11 microM for female volunteers). At the same age, male volunteers were shown to have higher tHcy levels than female volunteers. In addition, the mean concentrations of plasma tHcy in occluded coronary artery disease (13.62 +/- 5.43 microM) or in maintenance hemodialysis (21.28 +/- 4.32 microM) were statistically higher than in age-matched normal subjects (11.02 +/- 2.85 microM). This study emphasizes the significance of age and sex-associated difference in the plasma tHcy levels, and underlines the importance of the range for plasma homocysteine in normal Taiwanese subjects.

Adult↗

PubMed2000

MRP1 not MDR1 gene expression is the predominant mechanism of acquired multidrug resistance in two prostate carcinoma cell lines.

Multidrug resistant prostate cancer cell lines DU 0.03 and PC 0.03 were established from the parental prostate cancer cell lines DU145 and PC-3 respectively by stepwise selection in doxorubicin (DOX) from 0.001 to 0.03 &mgr;g/ml. As cells adapted to each concentration of DOX. the drug concentration was increased by 0.001 &mgr;g/ml. The chemosensitivity of each line was determined by growth inhibition assay. The DU 0.03 and PC 0.03 lines exhibit a 5-10-fold and 1.3-2.8-fold increase in resistance to anthracyclines, vinblastine (VLB) and mitozantrone (Mito), respectively. Verapamil (5 &mgr;M) partially reversed the resistance to the anthracycline and completely reversed the resistance to VLB and Mito. Drug kinetic studies measured by intracellular accumulation of (3)H-daunorubicin demonstrated a 3 fold decrease in the level of intracellular (3)H-daunorubicin in the PC 0.03 and DU 0.03 resistant lines compared with their respective parental line. This effect was partially reversed by 5 &mgr;M verapamil. The expression of MDR1 and MRP genes was analysed by Northern blotting and RT-PCR. P-glycoprotein (Pgp) and MRP protein were tested by immunocytochemistry staining using the monoclonal antibodies J-SB1. C219 and MRK16 (Pgp) and MRPm6 and MRPr1 (MRP). Neither Northern blot analysis nor the more sensitive RT-PCR demonstrated detectable MDR1 transcripts in any of the prostate cancer cell lines and the three Pgp monoclonal antibodies failed to reveal expression of Pgp. A 2-4-fold increase in MRP1 mRNA levels in the drug resistant DU 0.03 and PC 0.03 lines were demonstrated by both Northern blotting and RT-PCR consistent with the findings observed after staining by the two specific monoclonal antibodies, MRPm6 and MRPr1. Southern blot analysis demonstrated a 2-fold increase in the MRP1 gene copy number in the PC 0.03 line but not in the DU 0.03 line, suggesting that the overexpression of the MRP gene was regulated at the level of transcription in the latter line. We conclude that MRP1 not MDR1 overexpression. contributes to acquired drug resistance in these two prostate cancer cell lines. Prostate Cancer and Prostatic Diseases (2000) 3, 66-75

Journal Article↗

PubMed2000

Effect of nucleoside analogue therapy on duck hepatitis B viral replication in hepatocytes and bile duct epithelial cells in vivo.

BACKGROUND: Recent studies have implicated bile duct epithelial cells (BDEC) as a reservoir of hepatitis B virus (HBV) infection that may be particularly important in the development of post-liver transplant recurrence of hepatitis B. The aim of this study was to compare the effects of antiviral therapy on duck HBV (DHBV) expression in hepatocytes and BDEC and to determine if this was affected by biliary hyperplasia. METHODS: Ducklings congenitally infected with DHBV received penciclovir (10 mg/kg per day) treatment from 9 days of age. In order to mimic the biliary hyperplasia that often accompanies severe post-liver transplant HBV recurrence, half the animals underwent bile duct ligation. Duck HBV-DNA in serum was measured at day 1, and serum and liver DHBV-DNA were determined when the animals were killed on day 17. Intrahepatic expression of viral preS1 antigen and DHBV-DNA was measured by immunohistochemistry and in situ hybridization, respectively. RESULTS: Viraemia became undetectable in the penciclovir-treated animals at day 17, following 8 days of therapy. Examination of liver tissue revealed that all hepatocytes and the majority of BDEC contained DHBV preS1 antigen and DHBV-DNA. Penciclovir greatly reduced the intrahepatic viral burden, but there was no antiviral effect on viral markers within BDEC. Despite the increased number of BDEC after bile duct ligation, the same proportion of BDEC was seen to be infected, and this was unaffected by antiviral therapy. CONCLUSIONS: In the duck model with and without biliary hyperplasia, penciclovir controls DHBV replication and reduces viral burden in hepatocytes, but not in BDEC. The BDEC appear to be an important reservoir of virus that is relatively unaffected by antiviral treatment, and may play an important role in disease persistence and relapse following cessation of therapy.

Acyclovir↗

PubMed1999

nm23 protein expression and p53 immunoreactivity in cutaneous fibrohistiocytic tumors.

Recent data indicate that reduced expression of the 17-kD protein encoded by the nm23 gene may be important in the pathogenesis of several types of human tumors. Immunohistochemistry was performed using a murine monoclonal antibody, NCL-nm23 (Novocastra, 1:150 dilution) to investigate nm23 protein immunoreactivity in a group of locally aggressive cutaneous fibrohistiocytic tumors; dermatofibrosarcoma protuberans (DFSP) (n = 14) and atypical fibroxanthoma (AFX) (n = 7). Cases of dermatofibroma (DF) (n = 17) formed the benign control group. Comparison with p53 protein immunoreactivity in the same cases studied previously was made. Strong immunohistological expression of the nm23 protein was seen in most of the cases of DF (n = 15; 88%) in the form of strong cytoplasmic immunolabelling without nuclear staining. However, strong nm23 immunoreactivity was observed in only a minority of the cases of DFSP (n = 5; 36%) and AFX (n = 2; 29%). Statistically significant differences in nm23 immunoreactivity were found between DFSP and DF (p = 0.008, chi 2 test with continuity correction) and between AFX and DF (p = 0.015; chi 2 test with continuity correction). No significant difference was seen between DFSP and AFX (p = 0.87, chi 2 test with continuity correction). There was inverse correlation between nm23 and p53 immunoreactivity (r = 0.331; r2 = 0.109; p = 0.046; simple regression analysis). In summary, nm23 protein immunoreactivity is reduced in DFSP and AFX but not in dermatofibroma suggesting that reduced expression of the protein may be important in influencing the behavior of fibrohistiocytic tumors, although this is not well characterised. nm23 protein expression is also found to be inversely related to p53 immunohistological expression in these tumors.

Antigens, Neoplasm↗

PubMed1998

Surgery for primary hyperparathyroidism 1962-1996: indications and outcomes.

OBJECTIVE: To examine changes over the past three decades in the indications for, and outcomes of, surgery for primary hyperparathyroidism. DESIGN: Survey of a prospective hospital database. SETTING: Royal North Shore Hospital (a tertiary referral and university teaching hospital), Sydney, New South Wales, January 1962 to December 1996. PATIENTS: All 733 patients who underwent neck exploration for primary hyperparathyroidism. RESULTS: The annual number of parathyroidectomies increased virtually exponentially, from a mean of two in 1962-1969 to 73 in 1996. In the 1960s and 1970s, the most common indication for surgery was the presence of renal calculi (58% and 43%, respectively), but in the 1980s there was a marked increase in presentation of asymptomatic disease after biochemical screening (19%). In the 1990s, low bone mineral density detected by osteodensitometry has become the most common indication for surgery (31%). After initial operation, 11 patients (2%) had persistent hypercalcaemia, with five of these cured by reoperation--an overall failure rate of 1%. CONCLUSIONS: Surgery for primary hyperparathyroidism has become increasingly common, with low bone mineral density replacing renal calculi as the most common indication for surgery. Neck exploration in experienced hands results in an overall cure rate of 99%.

Adolescent↗

PubMed1998

A histological study of Denonvilliers' fascia and its relationship to the neurovascular bundle.

OBJECTIVE: To evaluate the anatomical relationship between the nerves and fasciae at the site of dissection in a radical retropubic prostatectomy. MATERIALS AND METHODS: Eight adult male (autopsy) en bloc specimens of bladder and rectum were examined histologically after staining with either haematoxylin and eosin or S-100 protein (as a specific nerve stain). RESULTS: All specimens showed Denovilliers' fascia to have no clearly defined layers and no definable lateral edge. No distinct neurovascular bundle was seen but nerves were scattered throughout the fasciae, including medially towards the midline. CONCLUSION: In radical retropubic prostatectomy, a piece of Denonvilliers' fascia is taken with the specimen, thus removing these nerves. The loss of these nerve fibres may explain the significant rate of erectile dysfunction after 'nerve-sparing' surgery.

Aged↗

PubMed1998

p53 protein immunoreactivity in fibrohistiocytic tumors of the skin.

Abnormal expression of the 53 kDa nuclear phosphoprotein produced by the p53 gene is observed in many human cancers. p53 nuclear immunoreactivity is found commonly in tumor cells. Immunohistochemistry was performed using a monoclonal antibody, DO-7 (DAKO, Denmark; cat. no. M7001; 1:100 dilution), to investigate p53 protein immunoreactivity in a group of cutaneous fibrohistiocytic tumors that are known to be locally aggressive. The study group consisted of dermatofibrosarcoma protuberans (DFSP) (n = 14) and atypical fibroxanthoma (AFX) (n = 7). Cases of dermatofibroma (DF) (n = 16) formed the benign control group. Intense nuclear immunostaining for p53 protein was observed in 71% of DFSP and 86% of AFX. None of the dermatofibromas showed strong p53 nuclear immunostaining. Statistical analyses revealed significant differences in p53 immunoreactivity between DFSP and DF (P = 0.0001, chi 2 test) and between AFX and DF (P = 0.0001, chi 2 test). In conclusion, increased p53 protein immunoreactivity is found in DFSP and AFX but not in DF. These differences in p53 immunoreactivity suggest that increased expression of the protein may be important in the pathogenesis of the more aggressive group of fibrohistiocytic tumors.

Dermatofibrosarcoma↗

PubMed1998

Parathyroid hormone-related protein mRNA and protein expression in multiple myeloma: a case report.

Multiple myeloma frequently leads to complications, such as osteolytic lesions, hypercalcemia, and pathological fractures. Increased bone resorption in myeloma is due to osteoclast activation. The nature of the osteoclast activator(s) remains unclear. We describe a case of multiple myeloma with marked hypercalcemia and skeletal complications that progressed rapidly despite chemotherapy. The patient had marked hypercalcemia at diagnosis (4.5 mmol/l), and elevated parathyroid hormone-related protein (PTHrP) levels were found in plasma. Analysis of the bone marrow trephine biopsy showed PTHrP gene transcription and protein in myeloma cells. These results provide strong evidence for the production of significant amounts of PTHrP by human myeloma cells. PTHrP has been measured as elevated in the plasma of patients with myeloma and might be an important contributor to the skeletal complications in this disease.

Aged↗

PubMed1997

Evaluation of extracellular lipid peroxidation in brain cortex of anaesthetized rats by microdialysis perfusion and high-performance liquid chromatography with fluorimetric detection.

A method for in vivo evaluation of lipid peroxidation in the extracellular space of anaesthetized rat brain cortex was developed. This method involved the use of microdialysis perfusion and high-performance liquid chromatography. The microdialysates, eluted from implanted probes, were reacted with thiobarbituric acid (TBA) prior to analysis by an HPLC system equipped with a fluorescence detector (excitation and emission wavelengths were 515 and 550 nm, respectively). Lipid peroxidation in the extracellular space was evaluated as the concentration of malondialdehyde, a lipid peroxidation end product which reacts with TBA to form a fluorescent conjugate. Significantly increased production of malondialdehyde following hydrogen peroxide perfusion (0.03%, 0.3% at a flow-rate of 1 microl/min) was observed in the brain cortex of anaesthetized rats.

Anesthesia↗

PubMed1997

Demonstration of duck hepatitis B virus in bile duct epithelial cells: implications for pathogenesis and persistent infection.

Hepatitis B virus (HBV) has been demonstrated in bile duct epithelial cells (BDEC) during chronic infection. The persistence of virus in BDEC may play an important role in disease pathogenesis, and may be at least partly responsible for the relapse phenomenon observed in antiviral treatments using nucleoside analogues. The aims of this study were to examine the morphological changes within the liver in the duck hepatitis B model following bile duct ligation (BDL), and to assess the effect of biliary hyperplasia upon viral DNA and proteins. Seven-day-old ducklings, congenitally infected with the duck hepatitis B virus (DHBV), were subject to BDL. The pathological and virological changes were then followed at 5, 10, 15, and 20 days after ligation. All results were compared with age-matched unligated control birds congenitally infected with DHBV. To assess the early morphological changes, additional animals were sacrificed at 1, 2, 3, and 4 days post-BDL. The proportion of DHBV-infected BDEC, was examined by immunohistochemistry and in situ hybridization. BDL induced rapid biliary hyperplasia, with a doubling time for BDEC of 1.3 days. The proliferated BDEC displayed immunohistochemical features identical to resting BDEC. More than 50% of BDEC in unligated controls, and more than 46% of proliferated BDEC in ligated animals were positive for DHBV DNA and structural proteins. The intensity of immunohistochemical staining and in situ hybridization signal in the BDEC was consistently greater than that of the hepatocytes, both before and after BDL. BDL induces biliary hyperplasia in the duck model, and BDEC division does not reduce the viral burden in infected cells.

Animals↗

PubMed1997

Temporal expression of PTHrP during endochondral bone formation in mouse and intramembranous bone formation in an in vivo rabbit model.

Expression of parathyroid hormone-related protein (PTHrP) messenger RNA (mRNA) and protein was investigated throughout the developmental progression of endochondral bone formation in mouse and intramembranous bone formation in an in vivo model in rabbit, using in situ hybridization and immunohistochemistry. Endochondral bone formation was investigated in a developing embryo, newborn, and adult mouse. In fetal long bones through to newborn (day 7), PTHrP mRNA and protein were consistently expressed in chondrocytes within the proliferative, transitional, and hypertrophic zones. In addition, high levels of PTHrP were also detected in osteoblasts on the surface of trabecular bone surfaces. Similarly, at the adult stage (week 7), PTHrP mRNA and protein were consistently expressed in chondrocytes at epiphyseal ends of the subarticular cartilage, within cortical periosteum, as well as in osteoblasts located at the metaphyseal trabecular bone surfaces. Using an in vivo intramembranous bone formation model in rabbits, expression of PTHrP mRNA and protein was demonstrated in preosteoblasts prior to trabecular bone formation (1-week bone harvest). As bone formed (2-, 3-, and 4-week bone tissue harvests), PTHrP mRNA and protein were highly expressed in actively synthesizing osteoblasts and in those osteocytes embedded within the superficial layers of the bone matrix. Lining osteoblasts and osteocytes buried deeply in the bone matrix displayed weak or no signal for PTHrP. The pattern of spatial and temporal expression of PTHrP demonstrated in cartilage cells and osteoblasts in the two systems suggests an important role of PTHrP in both endochondral and intramembranous bone formation.

Animals↗

PubMed1997

Expression of mdr1 and mrp in the normal B-cell homologue of B-cell chronic lymphocytic leukaemia.

B-cell chronic lymphocytic leukaemia (CLL) cells commonly express the multidrug resistance phenotype. The aim of this study was to establish whether the normal homologue in B-cell ontogeny of B-CLL also expressed the multidrug resistance (mdr) phenotype. Human tonsillar lymphocytes were sorted to yield two B-cell subsets based on the expression of CD19, CD5 and CD10. The normal homologue was represented by a population of B cells that was CD19 positive, CD10 negative and weakly expressed CD5. Based upon functional analysis and the detection of mdr1 mRNA by semi-quantitative PCR, these cells expressed the mdr phenotype. In contrast, functional multidrug resistance could not be demonstrated in CD19-positive CD10-positive cells with strong expression of CD5, nor could mdr1 mRNA be found in these cells. MRP was variably expressed in both B-cell subsets with no discernable differences in the pattern of expression. We conclude that normal B cells with a phenotype resembling that of B-CLL cells express the multidrug resistance phenotype.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed1996

Impact of complementary parathyroid scintigraphy and ultrasonography on the surgical management of hyperparathyroidism.

BACKGROUND: An ongoing debate exists regarding the relative merits of full versus limited neck exploration in the surgical management of parathyroid adenomata. The aim of this study was to assess the impact of localization studies on the subsequent surgical management of hyperparathyroidism. METHODS: The accuracy of complementary ultrasonography and 201TI/99mTc parathyroid subtraction scintigraphy in hyperparathyroidism was evaluated retrospectively during a 10-year period in patients referred for localization studies. Surgical and pathologic confirmation of the diagnosis was possible in 121 patients, and these data formed the basis of this study. Operative procedure, times, outcome, and complications were recorded. RESULTS: The sensitivity, specificity, and accuracy for combined scintigraphy and ultrasonography were 86%, 98%, and 96%, respectively. Limited neck exploration was performed in 61 of 121 patients, and 60 patients underwent full neck exploration. In primary hyperparathyroidism 59 of 105 patients underwent limited and 46 underwent full neck exploration with average operative times of 70 and 109 minutes, respectively. (p < 0.0001). Complications developed in five patients who underwent full neck exploration. CONCLUSIONS: Confident localization of parathyroid adenomata facilitated successful limited neck exploration in most of the patients, questioning the need for full neck exploration in all patients with primary hyperparathyroidism.

Adenoma↗

PubMed1995

Effect of ageing on human plasma glutathione concentrations as determined by high-performance liquid chromatography with fluorimetric detection.

A convenient method for the determination of reduced glutathione (GSH) and oxidized glutathione (GSSG) in human plasma by high-performance liquid chromatography with fluorescence detection is reported. This assay involves direct addition of human plasma to methanolic monobromobimane, for simultaneous protein precipitation and thiol derivatization. The assay was validated by addition of authentic GSH and GSSG to plasma samples. Plasma glutathione levels in Chinese male and female volunteers were found to decrease with increasing age (age groups 20-30, 30-40, 40-50, 50-60, and > 60; mean +/- S.E.M. 0.95 +/- 0.03, 0.77 +/- 0.02, 0.67 +/- 0.03, 0.51 +/- 0.02, 0.48 +/- 0.02 microM for male volunteers and 1.11 +/- 0.06, 0.76 +/- 0.03, 0.61 +/- 0.03, 0.53 +/- 0.04 and 0.43 +/- 0.04 microM for female volunteers). GSSG levels, in both males and females, did not show a correlation with age. There were no significant differences in GSH or GSSG levels among male and female volunteers of the same age group. These results suggest that elderly persons might be more susceptible to oxidative injury due to decreased plasma glutathione levels.

Adult↗

PubMed1995

Parathyroid hormone-related protein antigen localization distinguishes between mesothelioma and adenocarcinoma of the lung.

The distinction between pleural malignant mesothelioma and pulmonary adenocarcinoma remains a problem in diagnostic histopathology. Parathyroid hormone-related protein (PTHrP) has been demonstrated in the neoplastic cells of malignant mesotheliomata, using a polyclonal antiserum raised to synthetic PTHrP(1-16). In a series of 44 malignant mesotheliomata and 44 cases of pleural adenocarcinomata, PTHrP was localized immunohistochemically in 84 per cent of the mesotheliomata and in 11 per cent of the pleural adenocarcinomata. Normal and reactive mesothelium did not contain detectable PTHrP. The presence of PTHrP in a very high percentage of malignant mesotheliomata indicates the value of including it in the panel of antibodies utilized in the differential diagnosis of mesothelioma.

Adenocarcinoma↗

PubMed1995

The roles of reactive oxygen species and endogenous opioid peptides in ischemia-induced arrhythmia of isolated rat hearts.

Although the formation of oxygen-derived free radicals (or reactive oxygen species; ROS) and the release of endogenous opioid peptides (EOP) have been independently reported to be the major arrhythmogenic factors in ischemic hearts, possible relations between these two factors have seldom been investigated. Thus, we studied whether the ROS and EOP were related in the progression of ischemia-induced arrhythmias. Isolated rat hearts perfused in the Langendorff mode were treated with dynorphin A1-13 (kappa EOP receptor agonist), and/or allopurinol (xanthine oxidase inhibitor), before the onset of ischemia induced by ligating the left coronary arteries. Ischemic period lasted for 30 min, during which cardiac rhythms were recorded. At the end of ischemia, hearts were analyzed for the glutathione and ascorbate levels. Allopurinol (100 nmoles/heart) was effective in reducing the severity of arrhythmia (arrhythmia score: Mean +/- SEM 3.00 +/- 0.80 for allopurinol, 5.75 +/- 0.41 for placebo, p < 0.01), while dynorphin (10 micrograms/heart) potentiated the arrhythmia (6.71 +/- 0.52, p < 0.05 vs. placebo). Coadministration of allopurinol and dynorphin was capable of reducing arrhythmia (5.57 +/- 0.65) when compared with the administration of dynorphin alone (6.71 +/- 0.52, p < 0.05). Tissue oxidative stress was evaluated by the concentrations of glutathione (GSH) and ascorbate. Allopurinol did not significantly elevate tissue GSH concentrations (1.46 +/- 0.05 mumoles/g wet wt) in ischemic hearts, while dynorphin alone significantly decreased the GSH concentrations (0.96 +/- 0.08, p < 0.05) when compared with the placebo (1.32 +/- 0.03). The dynorphin-induced GSH decrease cannot be reversed by coadministration with allopurinol (0.90 +/- 0.104). Allopurinol significantly elevated tissue ascorbate levels (0.16 +/- 0.01) when compared with placebo (0.10 +/- 0.01, p < 0.05). Interestingly, dynorphin alone also elevated the tissue ascorbate concentrations (0.16 +/- 0.02). Coadministration of allopurinol and dynorphin further spiked the ascorbate levels (0.28 +/- 0.05, p < 0.01). In conclusion, the results suggested that ischemia-induced arrhythmia mechanisms might involve the formation of superoxide and other ROS, which were probably generated from the release of EOP (or EOP/EOP receptor interactions). Superoxide, the formation of which can be inhibited by allopurinol that exerted antiarrhythmic effect, was probably scavenged by ascorbate in myocardial ischemia. The ROS resulting from EOP/EOP receptor interactions were probably scavenged by glutathione system. Elevated ascorbate levels in dynorphin-treated hearts might result from the compensatory synthesis induced by decreased glutathione levels.

Allopurinol↗

PubMed1995

Transforming growth factor beta 1 stimulates bone formation and resorption in an in-vivo model in rabbits.

The influence of TGF beta 1 on bone was studied in a titanium device implanted into the tibia of rabbits. TGF beta 1 was infused via an Alzet osmotic pump calibrated to deliver at a rated of 200ng daily for 2 weeks before replacement. A hollow channel is incorporated into the device into which tissue can grow, and the histological sequence of events was observed over 6 weeks. In control samples, the rod-shaped piece of tissue at 2W consisted of spindle-shaped cells in the center, flanked at both ends by islands of trabecular bone lined by cuboidal osteoblasts and osteoclasts. By 4W, ingrowth of bone reached the center if the specimen, by which time, the bone surfaces were apposed by a single layer of flattened osteoblasts. However, osteoclastic resorption continued unabated so that by 6W, only a thin layer of cortical bone remained, enclosing a marrow cavity with hemopoietic elements. Significant differences were observed in samples continuously infused with TGF beta 1. At 2W, trabecular bone had reached further towards the center of the specimen and the granulation tissue was made up of cells that were more plump and cuboidal compared to the spindle cells of control sample. At 3W, there was increased bone volume and osteoid seams were thicker, covering a greater extent of the trabeculae surfaces. At 4W, the bony trabeculae were up to 3 times thicker than control trabeculae. There was very active bone resorption with many multinucleate osteoclasts and multilayered aggregates of cuboidal osteoblasts lining bony surfaces. Yet at 6W, the morphological appearance was similar to control samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗