Neuronal glucose transporter isoform 3 deficient mice demonstrate features of autism spectrum disorders.

Neuronal glucose transporter (GLUT) isoform 3 deficiency in null heterozygous mice led to abnormal spatial learning and working memory but normal acquisition and retrieval during contextual conditioning, abnormal cognitive flexibility with intact gross motor ability, electroencephalographic seizures, perturbed social behavior with reduced vocalization and stereotypies at low frequency. This phenotypic expression is unique as it combines the neurobehavioral with the epileptiform characteristics of autism spectrum disorders. This clinical presentation occurred despite metabolic adaptations consisting of an increase in microvascular/glial GLUT1, neuronal GLUT8 and monocarboxylate transporter isoform 2 concentrations, with minimal to no change in brain glucose uptake but an increase in lactate uptake. Neuron-specific glucose deficiency has a negative impact on neurodevelopment interfering with functional competence. This is the first description of GLUT3 deficiency that forms a possible novel genetic mechanism for pervasive developmental disorders, such as the neuropsychiatric autism spectrum disorders, requiring further investigation in humans.

Acupuncture for treating menopausal hot flushes: a systematic review.

OBJECTIVE: To assess the effectiveness of acupuncture as a treatment option for menopausal hot flushes. DESIGN: We have searched the literature using 17 databases from inception to October 10, 2008, without language restrictions. We included randomized clinical trials (RCTs) of acupuncture versus sham acupuncture. Their methodological quality was assessed using the modified Jadad score. RESULTS: In total, six RCTs could be included. Four RCTs compared the effects of acupuncture with penetrating sham acupuncture on non-acupuncture points. All of these trials failed to show specific effects on menopausal hot flush frequency, severity or index. One RCT found no effects of acupuncture on hot flush frequency and severity compared with penetrating sham acupuncture on acupuncture points that are not relevant for the treatment of hot flushes. The remaining RCT tested acupuncture against non-penetrating acupuncture on non-acupuncture points. Its results suggested favorable effects of acupuncture on menopausal hot flush severity. However, this study was too small to generate reliable findings. CONCLUSION: Sham-controlled RCTs fail to show specific effects of acupuncture for control of menopausal hot flushes. More rigorous research seems warranted.

Acupuncture for schizophrenia: a systematic review and meta-analysis.

BACKGROUND: Acupuncture is one of the most popular types of complementary/alternative medicine. It is sometimes used as a treatment for schizophrenia. AIMS: The objective of this review is to assess systematically the clinical evidence for or against acupuncture as a treatment for schizophrenia. METHODS: We searched 20 databases from their inception to May 2009 without language restrictions. All randomised clinical trials (RCTs) of acupuncture, with or without electrical stimulation or moxibustion for patients with schizophrenia were considered for inclusion. RESULTS: Thirteen RCTs, all originating from China, met the inclusion criteria. One RCT reported significant effects of electroacupuncture (EA) plus drug therapy for improving auditory hallucunations and positive symptom compared with sham EA plus drug therapy. Four RCTs showed significant effects of acupuncture for response rate compared with antipsychotic drugs [n = 360, relative risk (RR): 1.18, 95% confidence interval (CI): 1.03-1.34, p = 0.01; heterogeneity: tau(2) = 0.00, chi(2) = 2.98, p = 0.39, I(2) = 0%]. Seven RCTs showed significant effects of acupuncture plus antipsychotic drug therapy for response rate compared with antipsychotic drug therapy (n = 457, RR: 1.15, 95% CI: 1.04-1.28, p = 0.008, heterogeneity: tau(2) = 0.00, chi(2) = 6.56, p = 0.36, I(2) = 9%). Two RCTs tested laser acupuncture against sham laser acupuncture. One RCT found beneficial effects of laser acupuncture on hallucination and the other RCT showed significant effects of laser acupuncture on response rate, Brief Psychiatric Rating Scale and clinical global index compared with sham laser. The methodological quality was generally poor and there was not a single high quality trial. CONCLUSION: These results provide limited evidence for the effectiveness of acupuncture in treating the symptoms of schizophrenia. However, the total number of RCTs, the total sample size and the methodological quality were too low to draw firm conclusions. As all studies originated from China, international studies are needed to test whether there is any effect.

Acupuncture for Alzheimer's disease: a systematic review.

BACKGROUND: Acupuncture is often used as a treatment for dementia and is claimed to be effective in improving intelligence. AIMS: The objective of this review is to assess the clinical evidence for or against acupuncture as a treatment for Alzheimer's disease (AD). METHODS: We searched the literature using 17 databases from their inception to August 2008, without language restrictions. We included all randomised clinical trials (RCTs) of needle acupuncture to treat human patients suffering from AD. Methodological quality was assessed using the Jadad score. RESULTS: Three RCTs met all inclusion criteria. Two RCTs assessed the effectiveness of acupuncture on cognitive function compared with drug therapy. Their results suggested no significant effect in favour of acupuncture [n = 72, weight mean difference (WMDs), -0.55; 95% confidence intervals (CIs) -1.31 to 0.21, p = 0.15, heterogeneity: tau(2) = 0, chi(2) = 0.048, p = 0.49, I(2) = 0%]. Two RCTs tested acupuncture for activities of daily living (ADL). One RCT reported favourable effects of drug therapy compared with acupuncture for ADL, while the other failed to so. The meta-analysis of these data showed significant effects of drug therapy compared with acupuncture (n = 72, WMD, -1.29; 95% CIs: -1.77 to -0.80, p < 0.001, heterogeneity: tau(2) = 0, chi(2) = 0.17, p = 0.68, I(2) = 0%). CONCLUSION: Even though the number of studies is small, the existing evidence does not demonstrate the effectiveness of acupuncture for AD.

Study of structural and magnetic properties and heat induction of gadolinium-substituted manganese zinc ferrite nanoparticles for in vitro magnetic fluid hyperthermia.

This article outlines the synthesis of gadolinium (Gd)-doped manganese zinc ferrite magnetic nanoparticles (MNPs) as potential magnetic carriers for magnetic fluid hyperthermia (MFH). MNPs with high specific loss power (SLP; 146 W/g) have been developed and used for an in vitro hyperthermia study. The treatment of MFH is fruitful if there is an adequate number of MNPs in tumor cells with the highest SLP to rapidly generate heat while minimizing thermal injury to surrounding healthy tissue. X-ray diffraction patterns of the studied particles confirm the formation of a cubic spinel structure. Field emission scanning electron micrographs showed homogeneous distributions of particles with some agglomerates with a granular appearance. Transmission electron microscopy analysis showed the presence of agglomerated spherical particles at the surface. The substitution of Gd resulted in superparamagnetism at room temperature as confirmed by vibrating sample magnetometer analysis. The estimated saturation magnetization reduced from 48.6 to 28.2 emu/g with an increase in Gd concentration. However, the coercivity increased from 1093 Oe to 1597 Oe. Field cooled and zero field cooled measurements showed Curie temperatures from 315 to 326 K, as required for MFH applications. Cell viability measurements indicated that the MNPs are nontoxic to A549 cells for the studied concentrations of particle fraction and a contact time of up to 24 h. The interaction of the MNPs with A549 cells was highlighted from an image captured by an inverted microscope. In order to treat cancer in vivo, an in vitro hyperthermia study has initially been carried out with A549 cells.

Randomized, Open-Label, Phase IV, Korean Study of Kidney Transplant Patients Converting From Cyclosporine to Prolonged-Release Tacrolimus Plus Standard- or Reduced-Dose Corticosteroids.

BACKGROUND: This 24-week, multicenter, randomized, exploratory, comparative, open-label, phase-IV study assessed the safety and efficacy of prolonged-release tacrolimus (PR-T) with reduced-dose versus standard-dose corticosteroids in stable kidney transplant recipients in Korea after converting from cyclosporine-based therapy. METHODS: At baseline, patients were converted from cyclosporine-based to PR-T-based immunosuppression and randomized (1:1) to receive either corticosteroids maintained at prestudy dose (standard-dose group) or tapered from week 4 to 50% of the prestudy dose by week 12 (reduced-dose group). Patients were seen at baseline and weeks 1, 4, 12, and 24. The primary endpoint was change in estimated glomerular filtration rate (Modification-of-Diet-in-Renal-Disease-4) between baseline and week 24. Secondary endpoints included either acute rejection or patient-reported satisfaction with PR-T. Adverse events (AEs) were recorded. RESULTS: Overall, 150 patients were randomized into a reduced-dose group (n = 73) and a standard-dose group (n = 77). At week 24, mean ± standard deviation for corticosteroid dose was 2.5 ± 0.9 mg and 5.0 ± 1.3 mg, respectively. Mean change in estimated glomerular filtration rate from baseline to week 24 was +1.5 ± 9.1 mL/min/1.73 m2 (P = .1567) and +3.4 ± 10.6 mL/min/1.73 m2 (P = .0065), respectively, and not significantly different between groups. There were no acute rejection episodes. Most respondents (>70%) considered PR-T more convenient than cyclosporine. AE incidence was similar between groups. The most common AEs experienced by ≥3% of patients in either treatment group were gastrointestinal events (20.8% and 28.6% of patients receiving reduced- and standard-dose corticosteroids, respectively). Most AEs in both treatment groups were mild or moderate in severity. CONCLUSION: Renal function was maintained following conversion from cyclosporine to PR-T, irrespective of corticosteroid regimen; PR-T enables reduced corticosteroid dosage.

Acupuncture for rheumatoid arthritis: a systematic review.

The aim of this systematic review is to evaluate the available evidence, from randomized clinical trials (RCTs), of acupuncture for treating patients with RA. Systematic searches were conducted on 17 databases up to April 2008 without the language restriction. All RCTs of acupuncture, with or without electrical stimulation or moxibustion, for patients with RA were considered for inclusion. A total of 236 potentially relevant studies were identified and eight RCTs were included. Four RCTs compared the effects of manual or electro-acupuncture with penetrating or non-penetrating sham acupuncture and failed to show specific effects of acupuncture on pain [n = 88; weighted mean differences (WMD), 10 cm VAS -0.46; 95% CI -1.70, 0.77; P = 0.46; heterogeneity: tau(2) = 0.19; chi(2) = 2.38; P = 0.30; I (2) = 16%] or other outcome measures. One RCT compared manual acupuncture with indomethacin and suggested favourable effects of acupuncture in terms of total response rate. Three RCTs tested acupuncture combined with moxibustion, vs conventional drugs and failed to show that acupuncture plus moxibustion was superior to conventional drugs in terms of response rate (n = 345; RR 1.12; 95% CI 0.99, 1.28; P = 0.08; heterogeneity: tau(2) = 0.00; chi(2) = 1.34; P = 0.51; I(2) = 0%), pain reduction (n = 105; WMD, 10 cm VAS 1.53; 95% CI -0.57, 3.63; P = 0.15; heterogeneity: tau(2) = 1.18; chi(2) = 1.81; P = 0.18; I(2) = 45%) or joint swelling index (n = 105; WMD, 10 cm VAS 0.25; 95% CI -1.31, 1.82; P = 0.75; heterogeneity: tau(2) = 0.18;chi(2) = 1.14; P = 0.28; I(2) = 13%). In conclusion, penetrating or non-penetrating sham-controlled RCTs failed to show specific effects of acupuncture for pain control in patients with RA. More rigorous research seems to be warranted.

Fabrication of GaN doped ZnO nanocrystallines by laser ablation.

Here, we present the fabrication of pure and GaN doped ZnO nanocrystallines on Si(111) substrates by KrF excimer laser. The targets for the ablation have been prepared by conventional ceramic method. The fabricated nanocrystallines have been investigated by X-ray diffraction, photoluminescence and atomic force microscopy. The X-ray diffraction analysis shows that the crystalline size of pure ZnO is 36 nm and it is 41 nm while doped with 0.8 mol% of GaN due to best stoichiometry between Zn and O. Photoluminescence studies reveal that intense deep level emissions have been observed for pure ZnO and it has been suppressed for the GaN doped ZnO structures. The images of atomic force microscope show that the rms surface roughness is 27 nm for pure ZnO and the morphology is improved with decrease in rms roughness, 18 nm with fine crystallines while doped with 1 mol% GaN. The improved structural, optical and morphological properties of ZnO nanocrystalline due to GaN dopant have been discussed in detail.

Structural, electrical, and optical properties of Na-doped ZnO thin films deposited by pulsed laser deposition.

Na-doped ZnO thin films were deposited on quartz substrates at various temperatures by using pulsed laser deposition technique. An X-ray diffractometer and an atomic force microscope were used to investigate the structural and morphological properties of the thin films. A Hall effect measurement system was used to investigate the electrical properties of the thin films. A spectrophotometer was used to measure the transmittances of the thin films. The band gap energies of the thin films were calculated by linear fitting the sharp absorption edge for high-quality thin film. The band gap energies of the Na-doped ZnO thin films are nearly the same as the pure ZnO. A spectrometer was used to investigate the luminescent properties of the thin films. The thin film deposited at 200 degrees C had no near band edge emission and no deep-level emission. The NBE emission appeared and increased with increasing the growth temperature.

Auricular acupuncture for insomnia: a systematic review.

OBJECTIVE: Auricular acupuncture (AA) is a therapeutic method by which specific points on the auricle are stimulated to treat various conditions. AA is often recommended as treatment for insomnia. The aim of this systematic review was to evaluate data from randomised, placebo-controlled clinical trials testing the effectiveness of AA for treating insomnia. METHODS: We searched the literature using 18 databases from their inception to April 2008 without language restrictions. All prospective randomised clinical trials (RCTs) of AA for subjects with insomnia were considered. Methodological quality was assessed using the Jadad score. RESULTS: We identified 433 possible relevant articles, in which include 10 acceptable RCTs. The methodological quality of the trials was generally poor. Magnetic pellets AA was compared with placebo AA in three of the studies. The results suggested beneficial effects on sleep efficiency compared with placebo AA. One RCT tested needle AA compared with placebo AA and failed to show the effectiveness of AA. Four RCTs compared Semen Vaccariae or magnetic pellet AA with conventional drugs (estazolam or diazepam). Favourable effects for AA were found. Two RCTs tested thumbtack needle AA vs. no treatment suggested beneficial effects of AA on a sleep score. CONCLUSION: We conclude that, because of the paucity and of the poor quality of the data, the evidence for the effectiveness of AA for the symptomatic treatment of insomnia is limited. Further, rigorously designed trials are warranted to confirm these results.

Membrane glycoprotein differences between normal lactating mammary tissue and the R3230 AC mammary tumor.

Membrane glycoproteins have been studied in the normal lactating mammary gland and R3230 AC mammary tumor of the rat. Plasma membrane-enriched fractions were obtained from these tissues by discontinuous sucrose gradient centrifugation of a microsomal preparation from the tissue homogenates. The lightest membrane fractions (F-1 and F-2) have the greatest enrichment of plasma membrane markers, with a 14- to 20-fold purification of 5'-nucleotidase and Na+-K+ -adenosine triphosphatase over the homogenate values in both tumor and normal tissues for F-1. Electron microscopy shows smooth membrane vesicles for these fractions. Polypeptide analysis by acrylamide gel electrophoresis shows essentially the same patterns for F-1 and F-2 and only relatively minor differences between membrane components of tumor and normal tissues. Glycoprotein analysis of the polyacrylamide gels by periodate-Schiff staining indicates more dramatic differences. Membrane Fraction F-1 from normal tissue contains two major glycoproteins, GP-II and GP-III, while Fractions F-2 and F-3 contain an additional glycoprotein, GP-I, with a higher apparent molecular weight. In the tumor, the component corresponding to GP-III is decreased or absent and a new component GP-IV is seen at a lower apparent molecular weight.

Species variability in the modification of erythrocyte surface proteins by enzymatic probes.

Bovine and equine erythrocytes have been studied by three different surface modification techniques to investigate the accessibility of the surface components to the external medium. Lactoperoxidase labeling of equine erythrocytes results in a significant labeling of only one membrane component, a 100 000-mol.wt polypeptide corresponding to the membrane-spanning Component III of human erythrocytes. The major sialoglycoprotein of the equine erythrocyte is not labeled. This is in contradistinction to the situation for human and bovine cells, where both components are labeled. The equine membrane sialoglycoprotein is also not markedly affected by pronase, chymotrypsin or trypsin treatment of whole cells under the treatment conditions used, although it can be cleaved by pronase in isolated membranes. Experiments with the isolated glycoprotein show that its cleavage by trypsin is quite selective, whereas cleavage by pronase and chymotrypsin is much more extensive. Labelling of bovine red cells by galactose oxidase treatment followed by reduction with 3H-labeled borohydride yields radioactivity in only one major peak, that corresponding increase in labeling. Equine erythrocytes don not show significant labeling by this technique unless a neuraminidase pretreatment has been performed. Then only the major glycoprotein is labeled. Thus the equine glycoprotein is apparently inaccessible to the cell surface by standard surface modification methods, although it is clearly a surface component. These experiments point out some of the limitations of surface labeling and proteolysis methods in probing the accessibility of membrane components. The results suggest that apparent inaccessibility of the equine glycoprotein is due partially to its structure and partially to its localization in the membrane.

Studies on the active transport of calcium in human red cells.

The Ca(++) transport mechanism in the red cell membrane was studied in resealed ghost cells. It was found that the red cell membrane can transport Ca(++) from inside the cell into the medium against great concentration gradient ratios. Tracing the movement of (45)Ca infused inside red cells indicated that over 95% of all Ca(++) in the cells was transported into media in 20 min incubation under the optimum experimental conditions. The influence of temperature on the rate constant of transport indicated an activation energy of 13,500 cal per mole. The optimum pH range of media for the transport was between 7.5 and 8.5. As energy sources, ATP(1), CTP, and UTP were about equally effective, GTP somewhat less effective, and ITP least effective among the nucleotides tested. The Ca(++) transport does not appear to involve exchange of Ca(++) with any monovalent or divalent cations. Also, it is not influenced by oligomycin, sodium azide, or ouabain in high concentrations, which inhibit the Ca(++) transport in mitochondria or in sarcoplasmic reticulum. In these respects, the Ca(++) transport mechanism in the red cell membrane is different from those of mitochondria and the sarcoplasmic reticulum.

Active uptake of Ca++ and Ca plus,plus-activated Mg++ ATPase in red cell membrane fragments.

Isolated human red blood cell membrane fragments (RBCMF) were found to take up Ca(++) in the presence of ATP.(1) This ATP-dependent Ca(++) uptake by RBCMF appears to be the manifestation of an active Ca(++) transport mechanism in the red cell membrane reported previously (Schatzmann, 1966; Lee and Shin, 1969). The influences of altering experimental conditions on Ca(++)-stimulated Mg(++) ATPase (Ca(++) ATPase) and Ca(++) uptake of RBCMF were studied. It was found that pretreatment of RBCMF at 50 degrees C abolished both Ca(++) ATPase and Ca(++) uptake. Pretreatment of RBCMF with phospholipases A and C decreased both Ca(++) ATPase and Ca(++) uptake, whereas pretreatment with phospholipase D did not significantly alter either Ca(++) ATPase or Ca(++) uptake. Both Ca(++) ATPase and Ca(++) uptake had ATP specificity, similar optimum pH's, and optimum incubation temperatures. From these results, it was concluded that Ca(++) uptake is intimately linked to Ca(++) ATPase.

Annealing Dependence of Solution-Processed Ultra-Thin ZrOx Films for Gate Dielectric Applications.

Ultra-thin ZrOx thin films on Si substrates were prepared by sol-gel technique and processed with different methods (baked on hot plate at 150 °C, annealed at 500 °C in furnace, and photo-annealed under UV light). The decomposition of the organic groups and the formation of Zr-O bonding in the ZrOx thin films were confirmed by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. It is found that the ZrOx thin film annealed under UV light shows decent characteristics, including an ultra-small surface roughness, a low leakage current density of 10(-9) A/cm2 at 1 MV/cm, a large breakdown electric field of 9.5 MV/cm, and a large areal capacitance of 775 nF/cm2.

Antiproteinuric Effects of Green Tea Extract on Tacrolimus-Induced Nephrotoxicity in Mice.

INTRODUCTION: It has been reported that proteinuria is an early predictive marker in detection of tacrolimus (TAC) nephrotoxicity. The aim of this study was to investigate the antiproteinuric effects of green tea extract (GTE) on TAC-induced acute nephrotoxicity in mice. METHODS: The mice (n = 20) were divided into 4 groups (n = 5 per group); control group mice were intraperitoneally (IP) injected with 0.9% saline, TAC group mice were IP injected with TAC 1 mg/kg, and inducible nitric oxide synthase (iNOS) inhibitor group mice were given in addition NG-nitro-L-arginine-methyl ester 12 mmol/L by subcutaneous injection. TAC-GTE group mice were given TAC by IP injection and GTE 100 mg/kg by subcutaneous injection. RESULTS: The 24-hour urine protein amounts were significantly increased in TAC group mice (36.1 ± 9.9 mg/d) compared with control group mice (13.3 ± 5.4 mg/d) and significantly decreased in TAC-GTE group mice (19.1 ± 6.9 mg/d, P < .01) compared with TAC group mice. The nitric oxide (NO) production by TAC was significantly suppressed by GTE and iNOS inhibitor injection. Renal tissue malondialdehyde (MDA) level was significantly increased in the TAC group compared with the control group and was significantly decreased in the TAC-GTE group compared with that of the TAC group. The antioxidant enzyme activities of superoxide dismutase and catalase were significantly suppressed in the TAC group compared with the control group and were restored in the GTE injection group. CONCLUSIONS: GTE treatment has beneficial antiproteinuric effects on TAC-induced acute renal injury in mice.

Glucose transporter GLUT3 in the rat placental barrier: a possible machinery for the transplacental transfer of glucose.

Glucose transfer across the placental barrier is crucial for fetal development. To investigate the role of glucose transporter isoforms in the transplacental transfer of glucose, we investigated the localization of glucose transporters GLUT1 and GLUT3 immunohistochemically in the rat placenta. In the labyrinth, the site of maternofetal exchange of substances, both GLUT1 and GLUT3 were present, whereas only GLUT1 was detected in the junctional region. In the labyrinthine wall, which lies between maternal and fetal circulations, GLUT3 exhibited polarized localization; i.e. it was present at the plasma membranes of the maternal blood side in the syncytiotrophoblast layers. GLUT1 was concentrated at plasma membranes of the maternal and fetal blood sides of syncytiotrophoblast layers. The asymmetric distribution of GLUT3 across the placental barrier may suggest asymmetric transfer of glucose, which would be beneficial to provide a stable milieu for fetal development.

Direct gene transfer into rat liver cells by in vivo electroporation.

In vivo electro-transfection efficiency and manner of transferred gene expression were investigated by fluorescence microscopic image analysis. Green fluorescent protein (GFP) gene was used as the genetic marker. Electroporation was carried out on the liver of live rats by use of disk electrodes mounted in the tips of tweezers, which were directly pressed onto the surface of a liver lobe in situ. Electroporation with eight electric pulses of 50 ms in duration at 50 V gave a good efficiency of transfection as judged by the induced GFP expression. Bright fluorescence of GFP appeared as dots, which were scattered around the area damaged by electroporation. The transfection efficiency increased as the amount of injected DNA was increased. The results indicate that the amount of induced gene expression can be controlled. Estimation of the efficiency of electro-gene transfer using the fluorescence of GFP and digital analysis of microscopic images was useful to determine the optimum conditions for local gene therapy in tissues and organs.

Drug targeting using thermally responsive polymers and local hyperthermia.

We report a new thermal targeting method in which a thermally responsive drug carrier selectively accumulates in a solid tumor that is maintained above physiological temperature by externally applied, focused hyperthermia. We synthesized two thermally responsive polymers that were designed to exhibit a lower critical solution temperature (LCST) transition slightly above physiological temperature: (1) a genetically engineered elastin-like polypeptide (ELP) and (2) a copolymer of N-isopropylacrylamide (NIPAAm) and acrylamide (AAm). The delivery of systemically injected polymer-rhodamine conjugates to solid tumors was investigated by in vivo fluorescence video microscopy of ovarian tumors implanted in dorsal skin fold window chambers in nude mice, with and without local hyperthermia. When tumors were heated to 42 degrees C, the accumulation of a thermally responsive ELP with a LCST of 40 degrees C was approximately twofold greater than the concentration of the same polymer in tumors that were not heated. Similar results were also obtained for a thermally responsive poly(NIPAAM-co-AAm), though the enhanced accumulation of this carrier in heated tumors was lower than that observed for the thermally responsive ELP. These results suggest that enhanced delivery of drugs to solid tumors can be achieved by conjugation to thermally responsive polymers combined with local heating of tumors.

Preparation of 153Sm-chitosan complex for radiation synovectomy.

A samarium 153-chitosan complex was prepared by simply mixing acidic solutions of chitosan and (153)SmCl(3). When a solution of this complex was injected into the knee joints of rabbits, minimal extra-articular leakage was observed. This can be attributed to the rapid change in the pH of the complex solution from acidic to neutral, resulting in the formation of gel followed by the subsequent retention in the administered site. Thus, the complex solution represents a promising candidate for radiation synovectomy.