Intraarticular injection of a Tin-117 m radiosynoviorthesis agent in normal canine elbows causes no adverse effects.

This longitudinal prospective exploratory study used serial measurements in five dogs to evaluate safety and retention of a tin-117 m (117m Sn) colloid after intra-articular injection in normal elbow joints. Each dog was deemed healthy based on physical examination, laboratory results, and radiographic evaluation of both elbows. While anesthetized, each received an MRI of both elbows, followed by fluorine-18 fluorodeoxyglucose positron emission tomography scans of both elbow joints and associated lymph nodes. Joint fluid (0.5-1.0 mL) was withdrawn aseptically from the left elbow joint, followed by intra-articular injection of 117m Sn colloid (92.5 MBq; 1-1.5 ml). Post-injection assessments included blood counts, serum chemistry panels, urinalyses, radiographs, joint fluid analyses, MRI/positron emission tomography scans, scintigraphy, and biodistribution scans. On day 45-47, each dog was euthanized and a complete postmortem examination was performed. Tissue samples were submitted for histopathology and radioisotope retention studies. Left elbow joints were decalcified and sectioned for future autoradiography. Scintigraphy, 1 day after injection, indicated slight radioisotope escape from the joint to regional lymph nodes. Serial blood, urine, feces, and organ counts indicated >99.1% of the 117m Sn activity was retained in the joint for 45-47 days. Radiation output levels were below patient release levels the day following injection. Maximum standard uptake value for the injected joint decreased. Joint fluid cytology was unchanged. No dog exhibited lameness during the study. Absence of joint damage and lack of systemic effects after injection of the 117m Sn colloid in normal canine elbow joints indicate that this agent may be safely used for radiosynoviorthesis in dogs with osteoarthritis.

Derivation of biomonitoring equivalent for inorganic tin for interpreting population-level urinary biomonitoring data.

Population-level biomonitoring of tin in urine has been conducted by the U.S. National Health and Nutrition Examination Survey (NHANES) and the National Nutrition and Health Study (ENNS - Étude nationale nutrition santé) in France. The general population is predominantly exposed to inorganic tin from the consumption of canned food and beverages. The National Institute for Public Health and the Environment of the Netherlands (RIVM) has established a tolerable daily intake (TDI) for chronic exposure to inorganic tin based on a NOAEL of 20 mg/kg bw per day from a 2-year feeding study in rats. Using a urinary excretion fraction (0.25%) from a controlled human study along with a TDI value of 0.2 mg/kg bw per day, a Biomonitoring Equivalent (BE) was derived for urinary tin (26 µg/g creatinine or 20 µg/L urine). The geometric mean and the 95th percentile tin urine concentrations of the general population in U.S. (0.705 and 4.5 µg/g creatinine) and France (0.51 and 2.28 µg/g creatinine) are below the BE associated with the TDI, indicating that the population exposure to inorganic tin is below the exposure guidance value of 0.2 mg/kg bw per day. Overall, the robustness of pharmacokinetic data forming the basis of the urinary BE development is medium. The availability of internal dose and kinetic data in the animal species forming the basis of the assessment could improve the overall confidence in the present assessment.

Effect of Sn addition on the corrosion behavior of Ti-7Cu-Sn cast alloys for biomedical applications.

The aim of this study was to investigate the effects of Sn content on the microstructure and corrosion resistance of Ti7CuXSn (x=0-5 wt.%) samples. The corrosion tests were carried out in 0.9 wt.% NaCl solution at 25 °C. The electrochemical corrosion behavior of the Ti7CuXSn alloy samples was evaluated using potentiodynamic polarization curves, electrochemical impedance spectroscopy (EIS), and equivalent circuit analysis. The resulting impedance parameters and polarization curves showed that adding Sn improved the electrochemical corrosion behavior of the Ti7CuXSn alloy. The Ti7CuXSn alloy samples were composed of a dual-layer oxide consisting of an inner barrier layer and an outer porous layer.

Liquid-solid phase transition alloy as reversible and rapid molding bone cement.

Acrylic bone cement has been an essential non-metallic implant used as fixing agent in the cemented total joint arthroplasty (THA). However, the currently available materials based mainly on polymethylmethacrylate (PMMA) still encounter certain limitations, such as time-consuming polymerization, thermal and chemical necrosis and troublesome revision procedure. Here from an alternative way, we proposed for the first time to adopt the injectable alloy cement to address such tough issues through introducing its unique liquid-solid phase transition mechanism. A typical cement along this way is thus made of an alloy Bi/In/Sn/Zn with a specifically designed low melting point 57.5 °C, which enables its rapid molding into various desired shapes with high plasticity and ultimate metallic behaviors. The fundamental characteristics including the mechanical strength, biocompatibility and phase transition-induced thermal effects have been clarified to demonstrate the importance of such alloy as unconventional cement with favorable merits. In addition, we also disclosed its advantage as an excellent contrast agent for radiation imaging on the bone interior structure which is highly beneficial for guiding the surgery and monitoring the therapeutic effects. Particularly, the proposed alloy cement with reversible phase transition feature significantly simplifies the revision of the cement and prosthesis. This study opens the way for employing the injectable alloy materials as reversible bone cement to fulfill diverse clinical needs in the coming time.

Development of in situ forming thermosensitive hydrogel for radiotherapy combined with chemotherapy in a mouse model of hepatocellular carcinoma.

This study evaluated a system for local cancer radiotherapy combined with chemotherapy. The delivery system is a thermosensitive hydrogel containing a therapeutic radionuclide ((188)Re-Tin colloid) and a chemotherapeutic drug (liposomal doxorubicin). The thermosensitive PCL-PEG-PCL copolymer was designed to spontaneously undergo a sol-gel phase transition in response to temperature, remaining liquid at room temperature and rapidly forming a gel at body temperature. A scanning electron microscope was used to observe the microstructure of the fully loaded hydrogel. Release of radionuclide and doxorubicin from the hydrogel was slow, and the system tended to remain stable for at least 10 days. After the intratumoral administration of Lipo-Dox/(188)Re-Tin hydrogel in mice with hepatocellular carcinoma (HCC), its retention by the tumor, spatiotemporal distribution, and therapeutic effect were evaluated. The residence time in the tumor was significantly longer for (188)Re-Tin loaded hydrogel than for Na (188)Re perrhenate (Na (188)ReO4). The hydrogel after thermal transition kept the radionuclide inside the tumor, whereas free (188)Re perrhenate ((188)ReO4) diffused quickly from the tumor. The tumor growth was more profoundly inhibited by treatment with Lipo-Dox/(188)Re-Tin hydrogel (with up to 80% regression of well-established tumors on day 32) than treatment with either (188)Re-Tin hydrogel or Lipo-Dox hydrogel. Therefore, this injectable and biodegradable hydrogel may offer the advantage of focusing radiotherapy and chemotherapy locally to maximize their effects on hepatocellular carcinoma.

Tin and fluoride as anti-erosive agents in enamel and dentine in vitro.

OBJECTIVE: To investigate the efficacy of an experimental tin- and fluoride-containing mouth rinse on progression of erosion in enamel and dentine in vitro. MATERIAL AND METHODS: Human enamel and dentine specimens were subjected to a cyclic demineralization and remineralization procedure for 10 days, with six 5-min demineralization periods per day. Erosive demineralization was performed with 0.05 M citric acid (pH 2.3). Except in the negative control group, the specimens were treated for 2 min with mouth rinses after the first and sixth demineralizations. An experimental tin-containing fluoride mouth rinse [125 mg/kg F(-) (amine fluoride), 375 mg/kg F(-) (NaF), 800 mg/kg Sn(2+) (SnCl(2))] and an experimental sodium fluoride mouth rinse (500 mg/kg F(-)) were used (both pH 4.5). A commercially available, tin-containing mouth rinse served as a positive control (pH 4.2, 409 mg/kg Sn(2+), 250 mg/kg F(-)). Tissue loss was determined profilometrically. RESULTS: The highest tissue loss was found in the negative control group, in both enamel and dentine. In enamel, the NaF solution showed almost no effect. Both tin-containing solutions significantly reduced tissue loss (positive control: 65%; 800 mg/kg Sn(2+): 78%; both p ≤ 0.001 compared to negative control). In dentine all mouth rinses significantly reduced tissue loss (positive control: 43%; 800 mg/kg Sn(2+): 53%; NaF: 40%; all p ≤ 0.001 compared to negative control). CONCLUSIONS: In enamel, the efficacy of mouth rinses depended on the compound used; tin-containing preparations were notably effective. In dentine, however, reduction of substance loss was nearly the same in all treatment groups.

Effect of stannous and fluoride concentration in a mouth rinse on erosive tissue loss in enamel in vitro.

The aim of this in vitro study was to investigate the influence of stannous and fluoride ion concentrations in various experimental solutions on erosion progression in enamel. Human enamel specimens were subjected to a cyclic de- and remineralisation procedure for 10 days, with six demineralisation periods per day, of 5 min each. Erosive demineralisation was performed with 0.05 M citric acid (pH 2.3). Except in the control group, specimens were treated for 2 min with test solutions after the first and the sixth demineralisation. Test solutions were: 1500 mg/L F(-) groups: group 1: 2800 mg/L Sn(2+); group 2: 2100 mg/L Sn(2+); group 3: 1400 mg/L Sn(2+); group 4: 700 mg/L Sn(2+); 1000 mg/L F(-) groups: group 5: 2100 mg/L Sn(2+); group 6: 1400 mg/L Sn(2+). All preparations were adjusted to pH 4.5. Tissue loss was determined profilometrically after the last experimental day. As expected, the greatest tissue loss (microm, mean+/-S.D.) was found in the control group (72.6+/-11.5). All test solutions were able to reduce tissue loss significantly (p

Development of a thermosensitive hydrogel system for local delivery of (188)Re colloid drugs.

A novel internal radiation therapy (IRT) mode intended for controlled local delivery of (188)Re-Tin colloid was developed by using chitosan-based thermosensitive hydrogel. Chitosan (C) and beta-glycerophosphate (beta-GP) were used to prepare the thermosensitive hydrogel (C/GP). The prepared C/GP hydrogel featured a rapid sol-gel transition within 5min after it was brought into an environment of 37 degrees C. (188)Re-Tin colloid was prepared with labeling efficiency of 93.9+/-0.6%, and could be increased to more than 98% following centrifugation. The average particle size of (188)Re-Tin colloid was 12.1+/-1.2microm, with only 7.2+/-1.5% less than 1microm. Scintigraphic study showed that (188)Re-Tin colloid contained in the C/GP hydrogel was localized (>91%) around the injection site for up to 48h post injection, verifying the intended function of the IRT design. The developed novel form of IRT in this study could be an effective treatment mode for regional radiotherapy.

Dietary intake of tin in Japan, and the effects on intake of canned food and beverage consumption.

The study reported herein was initiated to examine dietary tin intake (Sn-D) in Japan to elucidate the possible effects of consumption of canned food (including beverages) on Sn-D, and to compare the intake among regions and between the two sexes in reference to the current provisional tolerable weekly intake and intake in other countries. Urinary tin levels (Sn-U) were also studied. Duplicate diet samples (24 h) together with records of food intake were collected in 1999-2004 from 111 adult residents in four areas of Japan. After exclusion of incomplete samples, 95 valid samples were subjected to determination of tin by inductively coupled plasma mass spectrometry (ICP-MS) after acid digestion. Among the 95 cases, 37 women additionally provided urine samples. Distribution of Sn-D was markedly skewed. Median Sn-D was 5.6 microg day(-1) for total subjects, which was about one-tenth of the values previously reported for the Japanese population; the difference was most probably attributable to the difference in the methods of determination. Consumption of canned foods led to a substantial increase in Sn-D. Thus, the median Sn-D for canned food consumers of 35.7 microg day(-1), was eight-fold higher than the median Sn-D for non-consumers of 4.5 microg day(-1). Sn-U (as corrected for creatinine concentration) distributed log-normally with a geometric mean of 2.0 microg (g cr)(-1). No effect of canned food consumption was evident on Sn-U. When compared internationally, Sn-D for the Japanese population was substantially lower than Sn-D for populations in other industrialized countries.

Radiation synovectomy using 188Re-tin colloid improves knee synovitis as shown by MRI in refractory rheumatoid arthritis.

BACKGROUND: Radiation synovectomy is a useful local treatment for patients with refractory synovitis. We previously demonstrated the efficacy and safety of Re-tin colloid for treating rheumatoid arthritis patients with refractory knee synovitis. This open-label, prospective controlled study investigates magnetic resonance imaging (MRI) changes as well as clinical response in knees after receiving different radioactivities of intra-articular Re-tin colloid. METHODS: Sixteen patients with rheumatoid arthritis refractory to intra-articular corticosteroid therapy were treated with intra-articular injection of Re-tin colloid (555 MBq in six patients, 740 MBq in five, and 925 MBq in five). Contralateral knees were used as controls. Treatment efficacy and safety were evaluated 1, 3 and 6 months later. We compared the changes of synovial thickening and joint effusion between baseline and 6 months. Synovial thickness was measured by gadolinium-enhanced MRI. RESULTS: Pain intensities on a visual analogue scale were significantly lower (median pain reduction, 78.9%; P=0.0001), joint swelling improved (median, -1.5; P=0.001), range of motion increased (median, 6 degrees , P=0.005), and joint tenderness decreased (median, -1; P=0.005) in treated knees after 6 months. The control knees did not show any significant clinical improvement. At 6 months after therapy, synovial thickening of treated knees improved in 87.5% of patients (P<0.001), and synovial thicknesses were significantly decreased in treated knees (P=0.0067). Furthermore, reduction in synovial thickness was most noticeable in the group treated with 925 MBq (P=0.007). No abnormalities in leukocyte or platelet counts, liver function tests, or urine analysis were observed. CONCLUSION: Radiation synovectomy using Re-tin colloid in refractory rheumatoid arthritis patients improved MRI findings as well as clinical parameters.

Synthesis and characterization of Sn(IV) complexes of lower rim 1,3-diacid derivative of calix[4]arene and their protective effects on tissue oxidative stress and essential metal concentration in lead exposed male Wistar rats.

The two Sn(IV) complexes synthesized using calix[4]arene-1,3-di-acid derivative were characterized by analytical, (1)H, (13)C and (119)Sn NMR, matrix assisted laser desorption ionization mass, and (119)Sn Mossbauer techniques and found that the complexes are tetranuclear possessing structurally two different types of tin centers. These complexes were evaluated for their protective value against blood and tissue oxidative stress in lead exposed male albino rats of Wistar strain. The results suggest that the two tin complexes significantly protect changes in lead induced biochemical variables indicative of heme synthesis pathway and exhibit only moderate effect on tissue oxidative stress. The beneficial effects could be attributed mainly to the ability of Sn(IV) complexes in preventing absorption of lead to the target sites/tissues.

Metallic tin-induced lymphadenopathy in rat strains and hybrids.

Metallic tin powder, injected into Lewis rats obtained from three different sources, caused enlargement of the regional draining lymph nodes. The histopathology featured epithelioid cell granulomas around phagocytosed particles of tin and an intense hyperplasia of plasma cells. The same material injected into August rats enlarged the lymph nodes but the enlargement was caused by granulomas without a major concomitant plasma cell response. In most other strains, tin produced less lymph node enlargement and the plasma cell response was minimal. However, F1 hybrids of Lewis rats with either the August, Brown-Norway (BN), or Dark Agouti (DA) strains developed plasma cell hyperplasia similar to that seen in the parental Lewis strain. The response to tin was the same whether the tin was injected into the feet or into the peritoneal cavity. Thus, the lymph node response to metallic tin varied from a slight, banal response to insoluble foreign particles, to an exuberant granulomatous hyperplasia, to an intense plasmacellular hyperplasia, depending on the genetic characteristics of the subjects.

Response of L-929 fibroblasts, human gingival fibroblasts, and human tissue mast cells to various metal cations.

Recent data suggest that under certain conditions, various metal cations are released from dental alloys. These ions may produce adverse effects in various cell types in vivo. In this study, the cytopathogenic effects of 13 metal cations on murine L-929 fibroblasts, human gingival fibroblasts, and human tissue mast cells were analyzed in vitro. Several metal cations (dose range, from 0.0033 to 1.0 mmol/L) were found to induce dose-dependent inhibition of 3H-thymidine incorporation into cultured fibroblasts. The rank order of potency (lowest observed effect level, LOEL) for L-929 fibroblasts was: Ag+ > Pt4+ > Co2+ > In3+ > Ga3+ > Au3+ > Cu2+ > Ni2+ > Zn2+ > Pd2+ > Mo5+ > Sn2+ > Cr2+. A similar rank order of potency was obtained for primary human gingival fibroblasts: Pt4+ > Ag+ > Au3+ > In3+ > Ga3+ > Ni2+ > Co2+ > Zn2+ > Cu2+ > Cr2+ > Pd2+ > Mo5+ > Sn2+. In primary human mast cells, Ag+ and Au3+ caused dose-dependent toxic histamine release, whereas the other metal cations were ineffective over the dose range tested. To investigate the mechanism of metal cation-induced effects, we performed DNA as well as electron microscopic analyses on cultured fibroblasts. Both the DNA pattern and the ultrastructure of L-929 cells and gingival fibroblasts after exposure to cytopathogenic metal cations revealed signs of necrosis but no signs of apoptosis. Together, our data provide evidence that various metal cations produce dose-dependent cytopathogenic effects in distinct cell types, including human gingival fibroblasts and human tissue mast cells.(ABSTRACT TRUNCATED AT 250 WORDS)

High tin intake reduces copper status in rats through inhibition of copper absorption.

The mechanism underlying the reduced Cu status in rats fed on a high-Sn diet was investigated. Male rats aged 4 weeks were fed ad lib. on purified diets containing either 1 or 100 mg Sn/kg and demineralized water for a period of 4 weeks. The high-Sn diet had no effect on feed intake, body-weight gain or weight of liver and kidney but significantly reduced Cu concentrations in plasma, liver and kidney. Biliary Cu excretion was decreased significantly in rats fed on the high-Sn diet. Apparent Cu absorption (Cu intake-faecal Cu) was not affected by the high-Sn diet, but the estimate of true Cu absorption (Cu intake-(faecal Cu-biliary Cu)) was significantly reduced. We conclude that high Sn intake reduces Cu status in rats through inhibition of Cu absorption. The decreased biliary Cu excretion observed on the high-Sn diet is a result of the reduced Cu absorption.

Combined effect of tin and lead on heme biosynthesis in rats.

The aim of the present study was to investigate the combined effect of tin (SnCl2) and lead Pb(CH3COO)2 on activity of heme biosynthesis enzymes [delta-aminolevulinic acid synthetase (ALA-S) and heme oxygenase] in liver and kidneys, as well as iron (Fe) and copper (Cu) concentration in serum of rats. The experiment was performed on female rats which received 2 mg Sn/kg and 3.5 mg Pb/kg separately and jointly intraperitoneally (ip) for 5 days and per os (po) at single dose (100 mg Sn/kg and 17.5 mg Pb/kg). Lead induced ALA-S in liver and kidney both after ip and po administration; tin, however, induced ALA-S only after ip administration in liver of rats. The activity of heme oxygenase was induced after Sn po and ip administration in liver and kidneys and Pb administration (ip) in kidneys. Sn and Pb administered jointly caused a significant increase of Cu (ip), whereas Sn (po) decreased this metal level in serum of rats. Kidneys proved to be the organ in which the highest degree of examined enzyme induction took place. Pb is responsible for ALA-S, whereas Sn is responsible for induction of heme oxygenase activity in this organ, especially after per os administration. No additive effect on ALA-S and heme oxygenase activities of Pb and Sn combined was noticed.

Antibody-targeted photolysis of bacteria in vivo.

We have evaluated the efficacy of antibody-targeted photolysis to kill bacteria in vivo using specific antibacterial photosensitizer (PS) immunconjugates. After infecting the dorsal skin in mice with Pseudomonas aeruginosa, both specific and nonspecific tin (IV) chlorin e6-monoclonal antibody conjugates were injected at the infection site. After a 15 min incubation period, the site was exposed to 630 nm light with a power density of 100 mW/cm2 for 1600 seconds. Irradiation resulted in a greater then 75% decrease in the number of viable bacteria at sites treated with a specific conjugate, whereas normal bacterial growth was observed in animals that were untreated or treated with a nonspecific conjugate. Antibody-targeted photolysis may be a selective and versatile tool for treating a variety of infections.

Iron, copper and zinc status in rats fed on diets containing various concentrations of tin.

The effects of various dietary concentrations of Sn (1, 10, 50, 100 and 200 mg/kg; added as SnCl2) on Fe, Cu and Zn status of rats were determined. After feeding the diets for 28 d body weight was not significantly affected, but there was a linear inverse response of feed intake. Plasma, kidney, spleen and tibia Fe concentrations as well as blood haemoglobin concentration and percentage transferrin saturation decreased in a linear dose-response manner as the level of dietary Sn increased. The addition of Sn to the diet depressed Cu status, as indicated by a significant inverse response of plasma, liver, kidney, spleen and tibia Cu levels. Plasma, kidney and tibia Zn concentrations were decreased by increasing levels of dietary Sn, but spleen and liver Zn concentrations were not significantly influenced. Fe, Cu and Zn status was influenced by dietary Sn concentrations lower than 50 mg/kg. If the results can be extrapolated to man it would follow that a high v. low Sn concentration in the human diet, which can be as distinct as 75 v. 2 mg/kg dry diet, may decrease plasma and tissue concentrations of Fe, Cu and Zn by up to 15%.

Comparison of tin and lead toxic action on erythropoietic system in blood and bone marrow of rabbits.

The aim of this work was to assess and compare morphological changes in blood and bone marrow of rabbits after per os (po) or intraperitoneal (ip) administration of equimolar doses of tin or lead. The experiment was performed on female rabbits that were divided into four groups of six animals each, and received stannous chloride SnCl2 x 2 H2O (Merck) or lead acetate Pb(CH3COO)2 (POCh Gliwice) in equimolar doses (ip--17/microM/kg) or per os (po--85/microM/kg). Group I was administered SnCl2 ip at the dose of 2 mg Sn/kg every day for 3 mo, group II Pb(CH3COO)2 ip at a dose of 3.5 mg Pb/kg every day for 3 wk, group III po SnCl2 (10 mg Sn/kg), and group IV po Pb(CH3COO)2 (17.5 mg Pb/kg), both for 4 mo. The morphological factors hemoglobin (Hb), hematocrit (Ht), erythrocyte (Ercs), and reticulocyte counts, MCV, MCH, MCHC, and erythropoietic system in bone marrow aspirates with sideroblast count, iron concentration, TIBC, and SI were estimated. Tin caused hemolytic anemia depending on abnormal iron utilization. After ip administration of tin, anemia was observed during the whole time of the study, whereas after po exposure, transient anemia was noticed. It has been proven that the mechanism of toxic action of tin on hematopoietic system is similar to the toxic effect of lead.

Protective effect of zinc on heme biosynthesis disturbances in rabbits after administration per os of tin.

In the present study the lowest p.o. doses of tin affecting heme biosynthesis in rabbits were determined and the protective effect of zinc on these disorders was evaluated. The experiment was performed on female rabbits who received per os single doses of SnCl2 x 2 H2O (10, 100, and 200 mg Sn/kg) and ZnSO4 (50 mg Zn/kg s.c.). The activities of delta-aminolevulinic acid dehydratase (ALA-D) in the whole blood, free erythrocyte propoporhyrins, urine delta-aminolevulinic acid, and coproporphyrins (CP-U) were determined. In animals administered tin at a dose of 100 mg Sn/kg, ALA-D activity decreased by about 80% and two- to threefold increases in the ALA and CP concentrations in urine were observed. A protective effect of zinc with respect to ALA-D activity was noticed in both groups (100 and 200 mg Sn/kg) after combined administration of both metals. Results of an interaction between zinc and tin were also observed to reduce ALA levels in urine, whereas zinc did not protect against an effect of tin on CP excretion.