Biodistribution of samarium-153-EDTMP in rats treated with docetaxel

Purpose: Many patients with metastatic bone disease have to use radiopharmaceuticals associated with chemotherapy to relieve bone pain. The aim of this study was to assess the influence of docetaxel on the biodistribution of samarium-153-EDTMP in bones and other organs of rats. Methods: Wistar male rats were randomly allocated into 2 groups of 6 rats each. The DS (docetaxel/samarium) group received docetaxel (15 mg/kg) intraperitoneally in two cycles 11 days apart. The S (samarium/control) group rats were not treated with docetaxel. Nine days after chemotherapy, all the rats were injected with 0.1ml of samarium-153-EDTMP via orbital plexus (25μCi). After 2 hours, the animals were killed and samples of the brain, thyroid, lung, heart, stomach, colon, liver, kidney and both femurs were removed. The percentage radioactivity of each sample (% ATI/g) was determined in an automatic gamma-counter (Wizard-1470, Perkin-Elmer, Finland). Results: On the 9th day after the administration of the 2nd chemotherapy cycle, the rats had a significant weight loss (314.50±22.09g) compared (p<0.5) to pre-treatment weight (353.66± 22.8). The % ATI/g in the samples of rats treated with samarium-153-EDTMP had a significant reduction in the right femur, left femur, kidney, liver and lungs of animals treated with docetaxel, compared to the control rats. Conclusion: The combination of docetaxel and samarium-153-EDTMP was associated with a lower response rate in the biodistribution of the radiopharmaceutical to targeted tissues. Further investigation into the impact of docetaxel on biodistribution of samarium-153-EDTMP would complement the findings of this study

Influence of Splenectomy on the Biodistribution of Technetium-99m Dimercaptosuccinic Acid (99mTc-DMSA) in Rats

This study aimed to evaluate if the splenectomy alters the biodistribution of 99mTc-DMSA and renal function in Wistar rats. The animals were separated in the groups: splenectomy (n = 6) and control (n = 6). After splenectomy (15 days), the administration of 0.1ml of 99mTc-DMSA IV (0.48 MBq) was carried out. Thirty minutes later, kidney, heart, lung, thyroid, stomach, bladder and femur and samples of blood were isolated. The organs were weighed, counted and the percentage of radioactivity -g (%ATI-g) determined. Serum urea and creatinine, hematocrit, leukocytes and platelets were measured. Statistics by t test (p<0.05) was done. There was a significant reduction in %ATI-g in kidney and blood (p<0.05) of splenectomized animals, a significant increase (p<0.05) of urea (88.8 ± 18.6 mg-dL) and creatinine (0.56 ± 0.08 mg-dL), compared to the controls (51.5±1.6, 0.37±0.02mg-dL, respectively), as well as increase in platelets and leucocytes, and hematocrit reduction. The analysis of the results indicates that in rats, splenectomy seems to alter the renal function and the uptake of 99mTc-DMSA

Biodistribution of the radiophamarceutical sodium pertechnetate (Na99mTcO4) after massive small bowel resection in rats

To evaluate the biodistribution of sodium pertecnetate (Na99mTcO4) in organs and tissues, the morphometry of remnant intestinal mucosa and ponderal evolution in rats subjected to massive resection of the small intestine. Methods: Twenty-one Wistar rats were randomly divided into three groups of 7 animals each. The short bowel (SB) group was subjected to massive resection of the small intestine; the control group (C) rats were not operated on, and soft intestinal handling was performed in sham rats. The animals were weighed weekly. On the 30th postoperative day, 0.l mL of Na99mTcO4, with mean activity of 0.66 MBq was injected intravenously into the orbital plexus. After 30 minutes, the rats were killed with an overdose of anesthetic, and fragments of the liver, spleen, pancreas, stomach, duodenum, small intestine, thyroid, lung, heart, kidney, bladder, muscle, femur and brain were harvested. The biopsies were washed with 0.9% NaCl.,The radioactivity was counted using Gama Counter WizardTM 1470, PerkinElmer. The percentage of radioactivity per gram of tissue (%ATI-g) was calculated. Biopsies of the remaining jejunum were analysed by HE staining to obtain mucosal thickness. Analysis of variance (ANOVA) and the Tukey test for multiple comparisons were used, considering p<0.05 as signifi cant. Results: There were no signifi cant differences in %ATI-g of the Na99mTcO4 in the organs of the groups studied (p>0.05). An increase in the weight of the SB rats was observed after the second postoperative week. The jejunal mucosal thickness of the SB rats was signifi cantly greater than that of C and sham rats (p<0.05). Conclusion: In rats with experimentally-produced short bowel syndrome, an adaptive response by the intestinal mucosa reduced weight loss. The biodistribution of Na99mTcO4 was not affected by massive intestinal resection, suggesting that short bowel syndrome is not the cause of misleading interpretation, if an examination using this radiopharmaceutical is indicated

Are Complications Associated With the Repiphysis(®) Expandable Distal Femoral Prosthesis Acceptable for Its Continued Use?

BACKGROUND: Reconstruction of the distal femur after resection for malignant bone tumors in skeletally immature children is challenging. The use of megaprostheses has become increasingly popular in this patient group since the introduction of custom-made, expandable devices that do not require surgery for lengthening, such as the Repiphysis(®) Limb Salvage System. Early reports on the device were positive but more recently, a high complication rate and associated bone loss have been reported. QUESTIONS/PURPOSES: We asked: (1) what are the clinical outcomes using the Musculoskeletal Tumor Society (MSTS) scoring system after 5-year minimum followup in patients treated with this prosthesis at one center; (2) what are the problems and complications associated with the lengthening procedures of this implant; and (3) what are the specific concerns associated with revision of this implant? METHODS: At our institute, between 2002 and 2007, the Repiphysis(®) expandable prosthesis was implanted in 15 children (mean age, 8 years; range, 6-11 years) after distal femoral resection for malignant bone tumors. During this time, the general indication for use of this implant was resection of the distal femur for localized malignant bone tumors in pediatric patients. Alternative techniques used for this indication were modular prosthetic reconstruction, massive (osteoarticular or intercalary) allograft reconstruction, or rotationplasty. Age and tumor extension were the main factors to decide on the surgical indication. Of the 15 patients who had this prosthesis implanted during reconstruction surgery, five died with the implant in situ or underwent amputation before 5 years followup and the remaining 10 were evaluated at a minimum of 5 years (mean, 104 months; range, 78-140 months). No patients were lost to followup. These 10 patients were long-term survivors and underwent the lengthening program. They were included in our study analysis. The first seven lengthening procedures were attempted in an outpatient setting; however, owing to pain and burning sensations experienced by the patients, the procedures failed to achieve the desired lengthening. Therefore, other procedures were performed with the patients under general anesthesia. We reviewed clinical data at index surgery for all 15 patients. We further analyzed the lengthening procedures, implant survival, radiographic and functional results, for the 10 long-term survivors. Functional results were assessed according to the MSTS scoring system. Complications were classified according to the International Society of Limb Salvage (ISOLS) classification system. RESULTS: Nine of the 10 survivors underwent revision of the implant for mechanical failure. They had a mean MSTS score of 64% (range, 47%-87%) before revision surgery. At final followup the 10 long-term surviving patients had an average MSTS score of 81% (range, 53%-97%). In total, we obtained an average lengthening of 39 mm per patient (range, 17-67 mm). Exact expansion of the implant was unpredictable and difficult to control. Nine of 10 of the long-term surviving patients underwent revision surgery of the prosthesis-eight for implant breakage and one for stem loosening. At revision surgery, six patients had another type of expandable prosthesis implanted and three had an adult-type megaprosthesis implanted. In five cases, segmental bone grafts were used during revision surgery to compensate for loss of bone stock. CONCLUSIONS: We could not comfortably expand the Repiphysis(®) prosthesis in an outpatient setting because of pain experienced by the patients during the lengthening procedures. Furthermore, use of the prosthesis was associated with frequent failures related to implant breakage and stem loosening. Revisions of these procedures were complex and difficult. We no longer use this prosthesis and caution others against the use of this particular prosthesis design. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Avaliação histomorfométrica do efeito do ultrasom pulsado nas falhas ósseas provocadas em fêmures de rato: estudo experimental

SILVA, J. S. P. Avaliação histomorfométrica do efeito do ultrasom pulsado nas falhas ósseas provocadas em fêmures de rato: estudo experimental . 2000. 85 f. Dissertação (Mestrado) – Faculdade de Medicina, Universidade de São Paulo. São Paulo, 2000.

Assessments of body composition and bone parameters of lactating rats treated with diet containing flaxseed meal (Linum usitatissinum) during post-weaning period

Introduction: There are few studies on body composition and the effects of diet on weight postpartum women. The aim was to evaluate the body composition and bone parameters in lactating rats treated with diet containing flaxseed flour during postweaning period. Methods: After weaning, the lactating rat were divided in control (n = 6) and experimental (F, n = 6) group, treated with 25% flaxseed flour diet. After 30 days, body composition by dual-energy X-ray absorptiometry, serum analysis, organs and intra-abdominal fat mass, femur and lumbar vertebra parameters were determined. Results: The groups showed similar food intake, body mass and bone parameters. While F group showed the following: lower body (-5%), gonadal (-17%), mesenteric (-23%) and intra-abdominal (-6%) fat mass. Increase of HDL-cholesterol (+10%) and lower glucose (-15%), triglycerides (P < 0.05, -37%) and cholesterol (P < 0.05, -21%). Conclusions: The findings highlight the effects of flaxseed for control of adiposity and to maintain a healthy biochemical profile during the postnatal period.

Are Complications Associated With the Repiphysis(®) Expandable Distal Femoral Prosthesis Acceptable for Its Continued Use?

BACKGROUND: Reconstruction of the distal femur after resection for malignant bone tumors in skeletally immature children is challenging. The use of megaprostheses has become increasingly popular in this patient group since the introduction of custom-made, expandable devices that do not require surgery for lengthening, such as the Repiphysis(®) Limb Salvage System. Early reports on the device were positive but more recently, a high complication rate and associated bone loss have been reported. QUESTIONS/PURPOSES: We asked: (1) what are the clinical outcomes using the Musculoskeletal Tumor Society (MSTS) scoring system after 5-year minimum followup in patients treated with this prosthesis at one center; (2) what are the problems and complications associated with the lengthening procedures of this implant; and (3) what are the specific concerns associated with revision of this implant? METHODS: At our institute, between 2002 and 2007, the Repiphysis(®) expandable prosthesis was implanted in 15 children (mean age, 8 years; range, 6-11 years) after distal femoral resection for malignant bone tumors. During this time, the general indication for use of this implant was resection of the distal femur for localized malignant bone tumors in pediatric patients. Alternative techniques used for this indication were modular prosthetic reconstruction, massive (osteoarticular or intercalary) allograft reconstruction, or rotationplasty. Age and tumor extension were the main factors to decide on the surgical indication. Of the 15 patients who had this prosthesis implanted during reconstruction surgery, five died with the implant in situ or underwent amputation before 5 years followup and the remaining 10 were evaluated at a minimum of 5 years (mean, 104 months; range, 78-140 months). No patients were lost to followup. These 10 patients were long-term survivors and underwent the lengthening program. They were included in our study analysis. The first seven lengthening procedures were attempted in an outpatient setting; however, owing to pain and burning sensations experienced by the patients, the procedures failed to achieve the desired lengthening. Therefore, other procedures were performed with the patients under general anesthesia. We reviewed clinical data at index surgery for all 15 patients. We further analyzed the lengthening procedures, implant survival, radiographic and functional results, for the 10 long-term survivors. Functional results were assessed according to the MSTS scoring system. Complications were classified according to the International Society of Limb Salvage (ISOLS) classification system. RESULTS: Nine of the 10 survivors underwent revision of the implant for mechanical failure. They had a mean MSTS score of 64% (range, 47%-87%) before revision surgery. At final followup the 10 long-term surviving patients had an average MSTS score of 81% (range, 53%-97%). In total, we obtained an average lengthening of 39 mm per patient (range, 17-67 mm). Exact expansion of the implant was unpredictable and difficult to control. Nine of 10 of the long-term surviving patients underwent revision surgery of the prosthesis-eight for implant breakage and one for stem loosening. At revision surgery, six patients had another type of expandable prosthesis implanted and three had an adult-type megaprosthesis implanted. In five cases, segmental bone grafts were used during revision surgery to compensate for loss of bone stock. CONCLUSIONS: We could not comfortably expand the Repiphysis(®) prosthesis in an outpatient setting because of pain experienced by the patients during the lengthening procedures. Furthermore, use of the prosthesis was associated with frequent failures related to implant breakage and stem loosening. Revisions of these procedures were complex and difficult. We no longer use this prosthesis and caution others against the use of this particular prosthesis design. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Biodistribution of technetium-99m pertechnetate after Roux-en-Y gastric bypass (Capella technique) in rats

The biodistribution of sodium pertechnetate, the most used radiopharmaceutical in nuclear medicine, has not been studied in details after bariatric surgery. The objective was to investigate the effect of Roux-en-Y gastric bypass (RYGB) on biodistribution of sodium pertechnetate (Na99mTc-) in organs and tissues of rats. Methods: Twelve rats were randomly divided into two groups of 6 animals each. The RYGB group rats were submitted to the Roux-en-Y gastric bypass and the control group rats were not operated. After 15 days, all rats were injected with 0.1mL of Na99mTc- via orbital plexus with average radioactivity of 0.66 MBq. After 30 minutes, liver, stomach, thyroid, heart, lung, kidney and femur samples were harvested, weighed and percentage of radioactivity per gram (%ATI/g) of each organ was determined by gama counter Wizard Perkin-Elmer. We applied the Student t test for statistical analysis, considering p<0.05 as significant. Results: Significant reduction in mean %ATI/g was observed in the liver, stomach and femur in the RYGB group animals, compared with the control group rats (p<0.05). In other organs no significant difference in %ATI/g was observed between the two groups. Conclusion: This work contributes to the knowledge that the bariatric surgery RYGB modifies the pattern of biodistribution of Na99mTc

Biodistribution of samarium-153-EDTMP in rats treated with docetaxel

Purpose: Many patients with metastatic bone disease have to use radiopharmaceuticals associated with chemotherapy to relieve bone pain. The aim of this study was to assess the influence of docetaxel on the biodistribution of samarium-153-EDTMP in bones and other organs of rats. Methods: Wistar male rats were randomly allocated into 2 groups of 6 rats each. The DS (docetaxel/samarium) group received docetaxel (15 mg/kg) intraperitoneally in two cycles 11 days apart. The S (samarium/control) group rats were not treated with docetaxel. Nine days after chemotherapy, all the rats were injected with 0.1ml of samarium-153-EDTMP via orbital plexus (25μCi). After 2 hours, the animals were killed and samples of the brain, thyroid, lung, heart, stomach, colon, liver, kidney and both femurs were removed. The percentage radioactivity of each sample (% ATI/g) was determined in an automatic gamma-counter (Wizard-1470, Perkin-Elmer, Finland). Results: On the 9th day after the administration of the 2nd chemotherapy cycle, the rats had a significant weight loss (314.50±22.09g) compared (p<0.5) to pre-treatment weight (353.66± 22.8). The % ATI/g in the samples of rats treated with samarium-153-EDTMP had a significant reduction in the right femur, left femur, kidney, liver and lungs of animals treated with docetaxel, compared to the control rats. Conclusion: The combination of docetaxel and samarium-153-EDTMP was associated with a lower response rate in the biodistribution of the radiopharmaceutical to targeted tissues. Further investigation into the impact of docetaxel on biodistribution of samarium-153-EDTMP would complement the findings of this study

Dynamic Coculture of a Prevascularized Engineered Bone Construct

The generation of functional, vascularized tissues is a key challenge for the field of tissue engineering. Before clinical implantations of tissue engineered bone constructs can succeed, in vitro fabrication needs to address limitations in large-scale tissue development, including controlled osteogenesis and an inadequate vasculature network to prevent necrosis of large constructs. The tubular perfusion system (TPS) bioreactor is an effective culturing method to augment osteogenic differentiation and maintain viability of human mesenchymal stem cell (hMSC)-seeded scaffolds while they are developed in vitro. To further enhance this process, we developed a novel osteogenic growth factors delivery system for dynamically cultured hMSCs using microparticles encapsulated in three-dimensional alginate scaffolds. In light of this increased differentiation, we characterized the endogenous cytokine distribution throughout the TPS bioreactor. An advantageous effect in the ‘outlet’ portion of the uniaxial growth chamber was discovered due to the system’s downstream circulation and the unique modular aspect of the scaffolds. This unique trait allowed us to carefully tune the differentiation behavior of specific cell populations. We applied the knowledge gained from the growth profile of the TPS bioreactor to culture a high-volume bone composite in a 3D-printed femur mold. This resulted in a tissue engineered bone construct with a volume of 200cm3, a 20-fold increase over previously reported sizes. We demonstrated high viability of the cultured cells throughout the culture period as well as early signs of osteogenic differentiation. Taking one step closer toward a viable implant and minimize tissue necrosis after implantation, we designed a composite construct by coculturing endothelial cells (ECs) and differentiating hMSCs, encouraging prevascularization and anastomosis of the graft with the host vasculature. We discovered the necessity of cell to cell proximity between the two cell types as well as preference for the natural cell binding capabilities of hydrogels like collagen. Notably, the results suggested increased osteogenic and angiogenic potential of the encapsulated cells when dynamically cultured in the TPS bioreactor, suggesting a synergistic effect between coculture and applied shear stress. This work highlights the feasibility of fabricating a high-volume, prevascularized tissue engineered bone construct for the regeneration of a critical size defect.

Influence of Splenectomy on the Biodistribution of Technetium-99m Dimercaptosuccinic Acid (99mTc-DMSA) in Rats

This study aimed to evaluate if the splenectomy alters the biodistribution of 99mTc-DMSA and renal function in Wistar rats. The animals were separated in the groups: splenectomy (n = 6) and control (n = 6). After splenectomy (15 days), the administration of 0.1ml of 99mTc-DMSA IV (0.48 MBq) was carried out. Thirty minutes later, kidney, heart, lung, thyroid, stomach, bladder and femur and samples of blood were isolated. The organs were weighed, counted and the percentage of radioactivity -g (%ATI-g) determined. Serum urea and creatinine, hematocrit, leukocytes and platelets were measured. Statistics by t test (p<0.05) was done. There was a significant reduction in %ATI-g in kidney and blood (p<0.05) of splenectomized animals, a significant increase (p<0.05) of urea (88.8 ± 18.6 mg-dL) and creatinine (0.56 ± 0.08 mg-dL), compared to the controls (51.5±1.6, 0.37±0.02mg-dL, respectively), as well as increase in platelets and leucocytes, and hematocrit reduction. The analysis of the results indicates that in rats, splenectomy seems to alter the renal function and the uptake of 99mTc-DMSA

Biodistribution of the radiophamarceutical sodium pertechnetate (Na99mTcO4) after massive small bowel resection in rats

To evaluate the biodistribution of sodium pertecnetate (Na99mTcO4) in organs and tissues, the morphometry of remnant intestinal mucosa and ponderal evolution in rats subjected to massive resection of the small intestine. Methods: Twenty-one Wistar rats were randomly divided into three groups of 7 animals each. The short bowel (SB) group was subjected to massive resection of the small intestine; the control group (C) rats were not operated on, and soft intestinal handling was performed in sham rats. The animals were weighed weekly. On the 30th postoperative day, 0.l mL of Na99mTcO4, with mean activity of 0.66 MBq was injected intravenously into the orbital plexus. After 30 minutes, the rats were killed with an overdose of anesthetic, and fragments of the liver, spleen, pancreas, stomach, duodenum, small intestine, thyroid, lung, heart, kidney, bladder, muscle, femur and brain were harvested. The biopsies were washed with 0.9% NaCl.,The radioactivity was counted using Gama Counter WizardTM 1470, PerkinElmer. The percentage of radioactivity per gram of tissue (%ATI-g) was calculated. Biopsies of the remaining jejunum were analysed by HE staining to obtain mucosal thickness. Analysis of variance (ANOVA) and the Tukey test for multiple comparisons were used, considering p<0.05 as signifi cant. Results: There were no signifi cant differences in %ATI-g of the Na99mTcO4 in the organs of the groups studied (p>0.05). An increase in the weight of the SB rats was observed after the second postoperative week. The jejunal mucosal thickness of the SB rats was signifi cantly greater than that of C and sham rats (p<0.05). Conclusion: In rats with experimentally-produced short bowel syndrome, an adaptive response by the intestinal mucosa reduced weight loss. The biodistribution of Na99mTcO4 was not affected by massive intestinal resection, suggesting that short bowel syndrome is not the cause of misleading interpretation, if an examination using this radiopharmaceutical is indicated

A rolling-gliding wear simulator for the investigation of tribological material pairings for application in total knee arthroplasty

Background: Material wear testing is an important technique in the development and evaluation of materials for use in implant for total knee arthroplasty. Since a knee joint induces a complex rolling-gliding movement, standardised material wear testing devices such as Pin-on-Disc or Ring-on-Disc testers are suitable to only a limited extent because they generate pure gliding motion only.Methods: A rolling-gliding wear simulator was thus designed, constructed and implemented, which simulates and reproduces the rolling-gliding movement and loading of the knee joint on specimens of simplified geometry. The technical concept was to run a base-plate, representing the tibia plateau, against a pivoted cylindrical counter-body, representing one femur condyle under an axial load. A rolling movement occurs as a result of the friction and pure gliding is induced by limiting the rotation of the cylindrical counter-body. The set up also enables simplified specimens handling and removal for gravimetrical wear measurements. Long-term wear tests and gravimetrical wear measurements were carried out on the well known material pairings: cobalt chrome-polyethylene, ceramic-polyethylene and ceramic-ceramic, over three million motion cycles to allow material comparisons to be made.Results: The observed differences in wear rates between cobalt-chrome on polyethylene and ceramic on polyethylene pairings were similar to the differences of published data for existing material-pairings. Test results on ceramic-ceramic pairings of different frontal-plane geometry and surface roughness displayed low wear rates and no fracture failures.Conclusions: The presented set up is able to simulate the rolling-gliding movement of the knee joint, is easy to use, and requires a minimum of user intervention or monitoring. It is suitable for long-term testing, and therefore a useful tool for the investigation of new and promising materials which are of interest for application in knee joint replacement implants. © 2010 Richter et al; licensee BioMed Central Ltd.