Permanent and removable implants for the brachytherapy of brain tumors
Thirty-seven patients harboring primary or metastatic brain tumors were treated with 40 implantations of radioactive sources (/sup 192/Ir, /sup 198/Au, or /sup 125/I) using stereotactic neurosurgical techniques. Most tumors had recurred after surgery, whole brain irradiation, and treatment with all feasible chemotherapeutic agents. Sixteen of the 40 implants were pregnant; 24 were mounted in plastic catheters for removal after the desired dose had been delivered. One or more sources were placed in each tumor to deliver 3500-7350 rad to the tumor's periphery for /sup 198/Au, 4,000-12,000 rad for /sup 192/Ir, and 3,000-20,000 rad for /sup 125/I. Three of the six patients treated with /sup 192/Ir had objective responses for 2, 4, and 12 months, and two stabilized for 8 and 11 months. Seven of the 11 patients treated with /sup 198/Au were evaluable: three responded for 3, 5, and 37 + months, one deteriorating patient with a recurrent tumor stabilized for 6 months, and two deteriorated despite treatment. One patient received an interstitial ''boost'' dose with /sup 198/Au after whole brain irradiation and stabilized for 15 months before developing spinal metastases. Six patients received permanent implants with low activity /sup 125/I. Three of these patients had blioblastomas or anaplastic astrocytomas; all continued to deteriorate despite the interstitial irradiation, presumably because the dose rat was too low. One patient with a low-grade astrocytoma (optic chiasm) responded dramatically to permanent, low activity /sup 125/I implants (11 + months). Another (hypothalamic glioma) had a permanent /sup 125/I implant, responded, as was stable at 9 months when external irradiation was administered. One patient with a suprasellar ''teratoid'' tumor stabilized for 10 months.
Successful treatment for permanent implant brachytherapy is based on accurate measurement of dosimetry parameters for the seed sources. Literature describes the application of various types of phantom to determine the AAPM TG-43 dosimetry parameters for permanent implant seeds. Previously we created a new type of phantom used to measure the dosimetry parameters of a high dose-rate 192Ir source. In this study, we modified the phantom to suit to a common type of 125I seed source (Sinko BT-125-1). The dose-rate constant, radial dose function and anisotropy function of this source were measured in detail and compared with the published values of other similar in-design 125I seed sources. The experimental results exhibit fairly small measurement uncertainties and good self-consistency. The modi...
We evaluated the efficacy of interstitial brachytherapy (IBT) using 125Iodine (125I) seeds for treatment of papillary tumors of the pineal region. Between September 2003 and September 2010, four patients (M/F?=?2/2; median age, 57.3?years; range 29.2?69.1?years) with papillary tumors of the pineal region underwent IBT using 125I seeds. Before brachytherapy two patients underwent endoscopic ventriculo-cisternotomy, because of occlusive hydrocephalus, and subsequent microsurgical resection was performed on one; three patients were primarily treated with IBT. Median tumor volume was 3.3?ml (range 1.6?4?ml), the tumor surface dose ranged between 50 and 65?Gy. For three patients the seeds were implanted permanently whereas one patient received temporary implants (28?days). The median follow-up ...
Isotope and Patient Age Predict for PSA Spikes After Permanent Prostate Brachytherapy
Purpose: To evaluate prostate-specific antigen (PSA) spikes after permanent prostate brachytherapy in low-risk patients. Methods and Materials: The study population consisted of 164 prostate cancer patients who were part of a prospective randomized trial comparing {sup 103}Pd and {sup 125}I for low-risk disease. Of the 164 patients, 61 (37.2%) received short-course androgen deprivation therapy. The median follow-up was 5.4 years. On average, 11.1 post-treatment PSA measurements were obtained per patient. Biochemical disease-free survival was defined as a PSA level of {<=}0.40 ng/mL after nadir. A PSA spike was defined as an increase of {>=}0.2 ng/mL, followed by a durable decline to prespike levels. Multiple parameters were evaluated as predictors for a PSA spike. Results: Of the 164 patients, 44 (26.9%) developed a PSA spike. Of the 46 hormone-naive {sup 125}I patients and 57 hormone-naive {sup 103}Pd patients, 21 (45.7%) and 8 (14.0%) developed a PSA spike. In the hormone-naive patients, the mean time between implantation and the spike was 22.6 months and 18.7 months for {sup 125}I and {sup 103}Pd, respectively. In patients receiving neoadjuvant androgen deprivation therapy, the incidence of spikes was comparable between isotopes ({sup 125}I 28.1% and {sup 103}Pd 20.7%). The incidence of spikes was substantially different in patients <65 years vs. {>=}65 years old (38.5% vs. 16.3%). On multivariate Cox regression analysis, patient age (p < 0.001) and isotope (p = 0.002) were significant predictors for spike. Conclusion: In low-risk prostate cancer, PSA spikes are most common in patients implanted with {sup 125}I and/or <65 years of age. Differences in isotope-related spikes are most pronounced in hormone-naive patients.
Purpose: To compare the urethral and prostate absolute and biologic effective doses (BEDs) for {sup 131}Cs and {sup 125}I prostate permanent implant brachytherapy (PPI). Methods and Materials: Eight previously implanted manually planned {sup 125}I PPI patients were replanned manually with {sup 131}Cs, and re-planned using Inverse Planning Simulated Annealing. {sup 131}Cs activity and the prescribed dose (115 Gy) were determined from that recommended by IsoRay. The BED was calculated for the prostate and urethra using an {alpha}/{beta} ratio of 2 and was also calculated for the prostate using an {alpha}/{beta} ratio of 6 and a urethral {alpha}/{beta} ratio of 2. The primary endpoints of this study were the prostate D{sub 90} BED (pD{sub 90}BED) and urethral D{sub 30} BED normalized to the maximal potential prostate D{sub 90} BED (nuD{sub 30}BED). Results: The manual plan comparison ({alpha}/{beta} = 2) yielded no significant difference in the prostate D{sub 90} BED (median, 192 Gy{sub 2} for both isotopes). No significant difference was observed for the nuD{sub 30}BED (median, 199 Gy{sub 2} and 202 Gy{sub 2} for {sup 125}I and {sup 131}Cs, respectively). For the inverse planning simulated annealing plan comparisons ({alpha}/{beta} 2), the prostate D{sub 90} BED was significantly lower with {sup 131}Cs than with {sup 125}I (median, 177 Gy{sub 2} vs. 187 Gy{sub 2}, respectively; p = 0.01). However, the nuD{sub 30}BED was significantly greater with {sup 131}Cs than with {sup 125}I (median, 192 Gy{sub 2} vs. 189 Gy{sub 2}, respectively; p = 0.01). Both the manual and the inverse planning simulated annealing plans resulted in a significantly lower prostate D{sub 90} BED (p = 0.01) and significantly greater nuD{sub 30}BED for {sup 131}Cs (p = 0.01), compared with {sup 125}I, when the prostate {alpha}/{beta} ratio was 6 and the urethral {alpha}/{beta} ratio was 2. Conclusion: This report highlights the controversy in comparing the dose to both the prostate and the organs at risk with different radionuclides.
The studies proposed were designed to investigate the relationship between transperineal permanent prostate implant quality, as modeled by the radiobiologicalquantifier of implant quality, tumor control probability (TCP), and treatment efficacy, as measured by prostatespecific antigen (PSA) failure free survival. It was hypothesized that TCP could be useful in identifying which patients, or group of patients, might be at an increased risk for treatment failure among patients receiving 125I transperineal permanent prostate brachytherapy (TPPB) as the sole modality of treatment for early or intermediate stage prostatic carcinoma. The formal statement of hypothesis was that the linear- quadratic tumor control probability model for monotherapeutic 125I transperineal permanent prostate brahytherapy correlates with prostate- specific antigen failure free survival. The specific aims were: [i]to implement the TCP model in a computerized treatment planning system for TPPB, using the recently recommended dose calculation formalism and benchmark data presented in AAPM TG43 and validate it, [ii]to compute and examine the relationship between TCP and PSA failure free survival for patients receiving monotherapeutic 125I TPPB, [iii]to investigate the influence of the definition of PSA failure on the relationship between TCP and PSA failure free survival rates, and [iv]to develop a method for improving the TCP model. The conclusions were: [i]the model as implemented using AAPM TG43 formalism, produced results which were similar to that calculated by the original model. TCP was demonstrated to correlate strongly and similarly with underdosed prostate volume in comparison to data published from the original model, [ii]an analysis of 125I implants demonstrated that patients stratified into the high TCP group had PSA failure free survival rates which were superior to the rates for patients in the low TCP group, regardless of which of the five definitions of PSA failure was applied to the study group, however, [iii]when different definitions of PSA failure were used to assess treatment efficacy, significantly different rates of PSA failure free survival were observed. Additionally, [iv]a method for calibrating the TCP model to produce a distribution of TCP's which more closely matched the calculated PSA failure free survival rates was derived.
PurposeWe describe how treatment factors influence biochemical freedom from failure, local control, freedom from metastasis and cause specific survival in patients treated with prostate brachytherapy. Materials and MethodsWe followed 2,111 men who underwent brachytherapy a median of 6 years (range 2 to 17). Median prostate specific antigen was 7 ng/ml. Of the men 1,455 (68.9%) had clinical stage T2a or less and 1,428 (67.6%) had Gleason score less than 7. A total of 1,171 patients (55.5%) received 125I, 221 (10.4%) received 103Pd and 719 (34.1%) received supplemental external beam irradiation combined with 103Pd. Post-implant dosimetry was done 30 days after implantation with doses converted to the biologically effective dose. Prostate biopsy was done 2 years after permanent prostate brach...
Ejaculatory Function After Permanent {sup 125}I Prostate Brachytherapy for Localized Prostate Cancer
Purpose: Ejaculatory function is an underreported aspect of male sexuality in men treated for prostate cancer. We conducted the first detailed analysis of ejaculatory function in patients treated with permanent {sup 125}I prostate brachytherapy for localized prostate cancer. Patients and Methods: Of 270 sexually active men with localized prostate cancer treated with permanent {sup 125}I prostate brachytherapy, 241 (89%), with a mean age of 65 years (range, 43-80), responded to a mailed questionnaire derived from the Male Sexual Health Questionnaire regarding ejaculatory function. Five aspects of ejaculatory function were examined: frequency, volume, dry ejaculation, pleasure, and pain. Results: Of the 241 sexually active men, 81.3% had conserved ejaculatory function after prostate brachytherapy; however, the number of patients with rare/absent ejaculatory function was double the pretreatment number (p < .0001). The latter finding was correlated with age (p < .001) and the preimplant International Index of Erectile Function score (p < .001). However, 84.9% of patients with maintained ejaculatory function after implantation reported a reduced volume of ejaculate compared with 26.9% before (p < .001), with dry ejaculation accounting for 18.7% of these cases. After treatment, 30.3% of the patients experienced painful ejaculation compared with 12.9% before (p = .0001), and this was associated with a greater number of implanted needles (p = .021) and the existence of painful ejaculation before implantation (p < .0001). After implantation, 10% of patients who continued to be sexually active experienced no orgasm compared with only 1% before treatment. in addition, more patients experienced late/difficult or weak orgasms (p = .001). Conclusion: Most men treated with brachytherapy have conserved ejaculatory function after prostate brachytherapy. However, most of these men experience a reduction in volume and a deterioration in orgasm.
PurposeSuboptimal dosage evaluated from postimplant dosimetry of prostate brachytherapy creates conundrum that needs resolution. This pilot study was undertaken to explore the feasibility of summing and visualizing radiation dosage from multimodality treatment. Methods and MaterialsFour weeks after 125I permanent prostate seed implant, CT scans were performed on the whole pelvis of patients using our standard protocol for prostate planning. The acquired CT data sets were reconstructed using different sizes of field of view (FOV). The images with limited FOV focusing on prostate were imported into Variseed (Varian Medical Systems, Inc., Palo Alto, CA) for postimplant evaluation, whereas images with full FOV were imported to Eclipse (Varian Medical Systems, Inc., Palo Alto, CA) treatment pla...
PurposeTo evaluate the efficacy of multimodality therapy consisting of hormone therapy (HT), brachytherapy (BT), and external beam radiotherapy (EBRT) in extraprostatic prostate cancer and identify factors with predictive value. Methods and MaterialsBetween June 1992 and October 2006, 97 patients with extraprostatic prostate cancer received permanent seed implant BT. Extraprostatic disease was defined by one or more of the following: positive seminal vesicle biopsy (n=56), positive lymph node dissection (n=8), or a clinical tumor stage of T3 (n=48). Treatment consisted of BT alone with 103Pd or 125I (n=4); HT and BT (n=3); BT and EBRT (n=2); or trimodality therapy with HT, BT, and EBRT (n=88). Median followup was 69 (range, 23-182) months. Freedom from biochemical failure (FBF) rates were ...
Seed migration in prostate brachytherapy depends on experience and technique
PurposeTo determine seed loss and pulmonary migration rate over time in permanent seed prostate brachytherapy. Methods and MaterialsWe analyzed the first 495 patients treated in our department. All patients were treated with loose 125I seeds with automated seed delivery system and real-time intraoperative planning. Pelvic fluoroscopic imaging was done 30 days after the implant. Patients were divided into five groups of 100 patients according to the order they were treated, and groups were compared using 2 test and one-way analysis of variance. ResultsA total of 22.8% of patients lost at least one seed. The highest percentage of patients losing any number of seeds was in the first 100. Thirty-eight percent lost at least one seed. This number decreased gradually and was only 9% in Patients 4...
Fourteen patients with locally recurrent prostate carcinomas after external beam irradiation received /sup 125/I seed implants at Stanford between 1975 and 1979. Clinical local control was obtained in 11 of the 14 patients for follow-up periods of 6 to 36 months. Eight remain without evidence of disease, but 2 of the 3 patients whose pelvic lymph nodes were involved by carcinoma have developed distant metastases. Complications, consisting of either cystoproctitis, urinary incontinence, or the development of a vesicorectal fistula occurred in 4 of the 14 patients. These complications were noted only in those patients who had implantation of high intensity /sup 125/I seeds (>0.50 mCi) into large prostatic volumes (greater than or equal to 50cc). No complications occurred in patients who received lower intensity /sup 125/I seed implants in smaller prostatic volumes. We conclude that /sup 125/I seed implants may be used in a second attempt to obtain local control after a local relapse following external beam irradiation, if the use of high intensity /sup 125/I sources and/or the implantation of large prostate volumes are avoided.
Purpose: To determine dosimetric risk factors for increased toxicity after permanent interstitial brachytherapy for prostate cancer. Patients and Methods: Quality of life questionnaires (Expanded Prostate Cancer Index Composite) of 60 and 56 patients were analyzed after a median posttreatment time of 6 weeks (A - acute) and 16 months (L - late). The corresponding CT scans were performed 30 days after the implant. The prostate, rectal wall, and base of seminal vesicles were contoured. Prostate volume, number of seeds and needles as well as dosimetric parameters were correlated with the morbidity scores. Results: For a prostate volume of 38{+-}12 cm{sup 3} (mean{+-}standard deviation), 54{+-}7 {sup 125}I sources (Rapid Strands {sup registered}, activity of 22.6{+-}3.0 MBq [0.61{+-}0.08 mCi]) were implanted using 20{+-}6 needles. Improved late urinary function scores resulted from a higher number sources per cm{sup 3} ({>=}1.35). A prostate D{sub 90}<170 Gy (A)/<185 Gy (L) and base of seminal vesicle D{sub 10}<190 Gy (A and L) were associated with higher urinary function scores. Late rectal function scores were significantly higher for patients with a prostate V{sub 200}<50% and V{sub 150}<75%. Patients with a prostate volume <40 cm{sup 3} reached better sexual function scores (A and L). A higher number of needles per cm{sup 3} ({>=}0.5) resulted in improved late urinary, bowel and sexual function scores. Conclusion: Quality of life after a permanent implant can be improved by using an adequate amount of sources and needles. With an increasing number of seeds per cm{sup 3}, dose homogeneity is improving. A prostate D{sub 90}<170 Gy and a base of seminal vesicle D{sub 10}<190 Gy (as an indicator of the dose to the bladder neck and urethral sphincter) can be recommended to maintain a satisfactory urinary function. (orig.)
Introduction: In order to improve tumor imaging, changes in the pharmacokinetics of 3-[{sup 123}I]iodo-{alpha}-methyl-L-tyrosine ([{sup 123}I]IMT), an artificial amino acid that exhibits high tumor accumulation, after probenecid (PBC) loading was studied in mice implanted with colon cancer DLD-1 cells using {sup 125}I-labeled IMT ([{sup 125}I]IMT). Methods: DLD-1-implanted KSN-slc nude male mice received 740 kBq of [{sup 125}I]IMT via the tail vein at 5 min after 50 mg/kg body weight PBC loading, and autoradiography was performed at 5, 15 and 30 min after injection. Male ddY mice then received 670 kBq of [{sup 125}I]IMT and 50 mg/kg 2-amino-bicyclo[2,2,1]heptane-2-carboxylic acid (BCH) or p-aminohippurate (PAH) via the tail vein, and kidney autoradiography was performed at 5 min after injection. In vitro inhibition study was then performed based on the accumulation mechanisms of [{sup 125}I]IMT in DLD-1, using 1 mM L-tyrosine, BCH, {alpha}-(methylamino)-isobutyric acid, N-benzoyl-{beta}-alanine, PBC, PAH, 2,4-dinitrophenol and sodium azide. Both Na{sup +}-dependent and Na{sup +}-independent uptake were investigated. Results: Higher tumor accumulation in PBC-loaded DLD-1-implanted mice was seen when compared to control mice. PAH and BCH, respectively, reduced renal accumulation in the tubule segment-2 (S2)-like and S1-like regions. We confirmed that [{sup 125}I]IMT transport is predominantly mediated by L-type amino acid transporter-1 in DLD-1 cells. Conclusions: [{sup 125}I]IMT uptake is mediated by organic anion and amino acid transporters in the kidney. Organic anion transporter inhibitors may yield better tumor images with good tumor/normal tissue radioactivity ratios if adequate administration plans are developed.
Abstract in spanish Objetivo: Revisar la experiencia con implantes permanentes de semillas de I-125 en carcinoma de próstata y el resultado a los 8 años de comenzar la técnica. Material y métodos: De 2002 a 2007 hemos realizado 250 implantes con braquiterapia de baja tasa con RapidStrand® y sistema de preplanificación. La edad media fue 68 años (49-78). El PSA medio fue 7,32 (2,31-14,6), 98% T1-T2a, 96% Gleason (more) ecibieron 46Gy de radioterapia externa). Un 42% recibieron hormonoterapia. Resultados: Con seguimiento medio de 48 meses, 14 pacientes (5,7%) tuvieron recaída bioquímica (RB). En 11 pacientes (4,5%) con teórica RB el PSA descendió espontáneamente sin tratamiento. La supervivencia actuarial sin recaída bioquímica a 5 años fue del 91% (92% bajo riesgo, 86% riesgo intermedio); 92 vs 81% en pacientes con PSA Abstract in english Introduction: We review the experience with prostate carcinoma patients treated with permanent implants of 125-I seeds and the outcome eight years after the beginning of this technique. Material and methods: From 2002 to 2007 we have performed 250 implants with LDR brachytherapy with RapidStrand® and preplanning system. Mean age was 68 (49-78). Mean PSA was 7.32 (2.31 - 14.6). T1-T2a was the stage in 98%, and Gleason (more) isk 19% (ten of them received 46Gy EBRT). Hormonal treatment was used in 42%. Results: With a mean follow-up of 48 months, 14 patients (5.7%) showed biochemical failure (BF). Eleven patients (4.5%) with theoretical BF were observed and PSA decreased without treatment. Actuarial PSA relapse-free survival at 5 years was 91%, (92% low risk, 86% intermediate cases), and 92% vs 81% with PSA
Purpose: A permanent prostate brachytherapy (PPB) program utilizing intraoperative inverse-planned dynamic dose-feedback was initiated without prior firsthand experience of alternative techniques. The purpose of this study is to assess the dosimetric learning curve associated with this approach. Methods and Materials: A total of 77 patients underwent PPB implants as monotherapy for localized prostate cancer to a prescription dose of 145 Gy with loose 125I seeds between December 2003 and June 2004. Intraoperative and postoperative dosimetric values, total implanted radioactivity, and operating room (OR) times were compared by sequential case number for all cases. Results: The median intraoperative dosimetric values were: D90 (the minimum dose to 90% of the prostate) = 170 Gy (range, 135-203 Gy), V100 (the volume of the prostate that receives 100% of the prescription dose) = 96% (range, 86-100), V150 = 66% (range, 34-86). Median postoperative dosimetric values were as follows: D90 = 168 Gy (range, 132-197 Gy), V100 = 95% (range, 86-99), V150 = 74% (range, 51-84). Median implanted activity was 0.79 mCi per cubic centimeter of prostate (range, 0.541-1.13). There was no significant correlation by case number on any postoperative dosimetric parameter studied. Door-to-door OR time was reduced from median 138 to 97.5 min per case at the end of the series with a correlation coefficient of -0.76 for the initial 28 cases. Conclusion: Satisfactory dosimetric parameters can be achieved from the outset without a learning curve effect in an appropriately trained environment. The learning curve for dynamic dose-feedback PPB in a clinic naive to other techniques is apparent in terms of OR time.
Is there a role for postimplant dosimetry after real-time dynamic permanent prostate brachytherapy?
Purpose: To evaluate the correlation of real-time dynamic prostate brachytherapy (RTDPB) dosimetry and traditional postimplant dosimetry for permanent prostate brachytherapy. Methods and Materials: A total of 164 patients underwent RTDPB for clinically confined prostate cancer. Of these 164 patients, 45 were implanted with {sup 103}Pd and 119 with {sup 125}I. Additionally, 44 patients underwent combined external beam radiotherapy and brachytherapy and 120 patients underwent brachytherapy alone. The postimplant dosimetry with computed tomography was performed at 4 weeks and compared with the RTDPB dose plan using the intraclass correlation coefficient. The millicurie/gram of the prostate volume and the percentage of the minimal dose to 90% of the prostate relative to the prescribed implant dose (D{sub 9}%) of the RTDPB patients was compared with 400 patients treated with a free-seed technique. Results: The mean D{sub 9}% achieved in the operating room and on the 3-week dose plan was 109% (range, 93-139%) and 105% (range, 88-140), respectively. The mean percentage of prostate volume receiving 100% of the prescribed minimal peripheral dose (V{sub 10}) achieved in the operating room and on the 3-week dose plan was 93% (range, 78-98%) and 91% (range, 64-98%), respectively. The intraclass correlation coefficient for each calculated relationship was 0.586 for D{sub 9} (p < 0.001), 1.19 for V{sub 10} (p = 0.135), 0.692 for the urethral D{sub 9} (p < 0.001), 0.602 for the maximal rectal dose (p < 0.001), 0.546 for D{sub 9} with {sup 125}I (p < 0.001), and 0.565 for D{sub 9} with {sup 103}Pd (p < 0.001). A 12% decrease was noted in the millicurie/gram of the isotope, with a 2.5% increase in the D{sub 9} comparing RTDPB and the free-seed technique. Conclusion: The results of this study demonstrated a correlation between the dose assessment obtained intraoperatively and postoperatively at 3 weeks. With reliable dose data available in the operating room, our results question the need for routine postimplant dose studies. Furthermore, patients treated with RTDPB received less radioactivity per gram of the prostate with a corresponding small increase in the D{sub 9}. Future analyses will assess variations in the inverse dose planning rules and the clinical correlation of patients undergoing RTDPB vs. older techniques for toxicity and biochemical outcomes.
Self-expandable stent loaded with {sup 125}I seeds: Feasibility and safety in a rabbit model
Objective: To evaluate technical feasibility and acute and subacute radiotolerance of a self-expandable stent loaded with {sup 125}I seeds in the rabbit esophagus. Methods: A self-expandable stent designed for esophageal application was made of 0.16 mm nitinol wire and loaded with {sup 125}I seeds (CIAE-6711). Twenty-seven stents with three different radioactive dosages (n = 9 in each dosage group) were implanted in the esophagus of healthy rabbits, while nine stents alone were used as controls. The stents were perorally deployed into the esophagus under fluoroscopic guidance. Radiological follow-up included plain chest film, CT scan, and barium esophagography which were undertaken in all rabbits of each group at 2, 4, and 8 weeks, respectively, which were correlated to histopathological findings. The stented esophageal segments along with their adjacent tissues were harvested for histopathological examinations. Results: The stent was successfully deployed into the targeted esophageal segment in all rabbits. Neither {sup 125}I seeds dislodged from the stent during the deployment, nor they did during the follow-up period. The greatest (16.2 Gy) absorbed dose was found in the tissue 10 mm from {sup 125}I seeds at 8 weeks. Slight epithelial hyperplasia on the stent surface and submucosal inflammatory process developed at 2 weeks, which reached the peak at 8 weeks after the procedure. Significant thickness of the esophageal muscular layer was found at 8 weeks only in the groups with {sup 125}I seeds. On radiologic follow-up, moderate strictures on both ends of the stents developed at 4 weeks and became severe at 8 weeks after the procedure in all groups. Conclusion: Deployment of a self-expandable stent loaded with {sup 125}I seeds is technically feasible and safe within the first 8 weeks. Acute and subacute radiotolerance of the treated esophagus and its adjacent tissues by {sup 125}I seeds is well preserved in a healthy rabbit model.
AbstractObjectives/Hypothesis: We aimed to evaluate the feasibility and effectiveness of postoperative 125I brachytherapy delivered by use of digital model obturators for recurrent or locally advanced maxillary cancers. Study Design: Retrospective study. Methods: From 2006 to 2008, 12 patients (seven females; median age, 65 years; range, 22-86 years) with recurrent or locally advanced maxillary cancers showing positive margins after surgery underwent 125I brachytherapy by use of digital model obturators and interstitial implants. The radioactivity was 18.5 to 33.3 MBq per seed, and the prescription dose was 80 to 160 Gy. Functional outcome of patients was evaluated by the Performance Status Scale (PSS) for head and neck cancer before and after brachytherapy. Results: The 125I seeds and dos...
Prostate brachytherapy seed migration to a left varicocele
PurposeTo report a rare case of seed migration to a left varicocele after transperineal interstitial prostate brachytherapy with loose iodine-125 (125I) seeds. Methods and MaterialsA 73-year-old man presented with a serum prostate-specific antigen level of 5.21ng/mL, Gleason score of 7 (3+4), and clinical T1c adenocarcinoma of the prostate. The patient underwent transperineal interstitial prostate brachytherapy with loose 125I seeds followed by external beam radiation therapy. Two weeks after seed implantation, a followup pelvic radiograph was obtained. One month after seed implantation, a pelvic computed tomography scan for postimplant dosimetric analysis was carried out. Subsequent ultrasound examination of the scrotum was undertaken. ResultsTwo weeks after seed implantation, an anteropo...
The purpose was to summarize the urinary, rectal, and sexual symptoms occurring during the first 12 months following [sup 125]I prostatic implantation. Thirty-one patients with Stage T[sub 1] or T[sub 2] prostatic carcinoma were evaluate for morbidity following computed tomography-guided transperineal [sup 125]I implants from 1988 to 1991. The median total activity used was 47 mCi (range 35-37 mCi). Toxicity was evaluated using a modification of the Radiation Therapy Oncology Group grading system. Nocturia was the most common treatment-related symptom, reported by 80% of patients within 2 months after implantation, and persisted at 12 months in 45% of the patients. Mild dysuria developed in 48% of patients within 2 months of implantation; two patients needed analgesics for their dysuria. Terazosin hydrochloride (2-10 mg qd) provided subjective improvement of urinary symptoms in seven of eight patients in whom it was tried. Rectal urgency, soft stools, and increased frequency of bowel movements was reported by 25% of the patients within 1-2 months after implantation. The incidence of assymptomatic rectal bleeding or ulceration occurring at any time after implantation was 47%, but resolved in all patients with expectant treatment. Self-limiting ulceration of the rectal mucosal occurred in 16%, but only one patient developed a prostato-rectal fistula, managed with an ileal conduit. Five of the 18 potent patients experienced discomfort on erection or ejaculation, beginning within several weeks of their implant. The discomfort resolved within 6 months in three of the patients, but persisted for 18 and 24 months in the other two. [sup 125]I implantation, as performed in this series, is generally associated with only mild-moderate genitourinary and rectal symptoms that may persist 6 months or more after implantation. 16 refs., 6 figs., 2 tabs.
PSA Kinetics and PSA Bounce Following Permanent Seed Prostate Brachytherapy
Purpose: To report the incidence, timing, and magnitude of the benign prostate-specific antigen (PSA) bounce after {sup 125}I prostate brachytherapy and correlate the bounce with clinical and/or dosimetric factors. Methods and Materials: From March 1999 to August 2003, a total of 292 men received {sup 125}I prostate brachytherapy without androgen deprivation or supplemental beam radiotherapy and have PSA follow-up >30 months. Implants were preplanned using transrectal ultrasound (TRUS) and performed under transrectal ultrasound/fluoroscopy guidance using preloaded needles. A PSA bounce is defined as an increase {>=}0.2 ng/ml with spontaneous return to prebounce level or lower. Results: Resolved PSA bounces were seen in 40% of men with follow-up >30 months. Median onset was 15 months, and median magnitude was 0.76 ng/ml. Magnitude >2 ng/ml was seen in 15%. The only clinical or dosimetric factor predictive of bounce in multivariate analysis was younger age. Median time to increasing PSA level indicative of failure was 30 months. Conclusions: Benign PSA bounces are common after {sup 125}I prostate brachytherapy, especially in younger men. An increase >2 ng/ml above the nadir was seen in 15%. Magnitude of increase does not distinguish bounce from failure. Time to the start of the PSA increase can be helpful, but is not absolute. The PSA bounce does not predict subsequent failure. Caution is advised in interpreting an early increasing PSA level in the first 30 months after {sup 125}I brachytherapy in favorable-risk patients.
Hemocompatibility investigation of the NiTi alloy implanted with tantalum.
A composite TiO(2)/Ta(2)O(5) nano-film has been formed on the NiTi shape memory alloy by Ta implantation. The wettability, protein adsorption, platelets adhesion and hemolysis tests are conducted to evaluate the hemocompatibility. The contact angle measurements showed that the surface of the NiTi alloy kept hydrophilic before and after Ta implantation, although the water contact angle increased with the increasing of implantation current. Both of the surface energy and the interfacial tension decreased after Ta implantation. The protein adsorption behavior was investigated by (125)I isotope labeling. The fibrinogen adsorption was enhanced by a high surface roughness or a large interfacial tension, while the albumin adsorption was insensitive to the surface modification. Platelet adhesion and activation were weakened and the hemolysis rate was reduced at least 46% after Ta implantation due to the decreased surface energy and improved corrosion resistance ability, respectively. PMID:21833606
Patients receiving /sup 125/I implantation and pelvic lymphadenectomy for clinically localized prostatic carcinoma were divided into two groups, with one group receiving a preoperative channel transurethral prostatectomy. The groups were matched according to clinical stage and histologic grade. Complications were classified as operative, short-term, and long-term. Although preoperative channel transurethral prostatectomy was associated with a greater incidence of surgical procedures after implantation, the overall complication rate did not differ between the two groups. The overall mortality rate and the incidence of progression of Stage C tumors did not differ between the two groups.
The decision to implant vena cava filters, either temporary or permanent, is difficult in young patients. We present the case of a young man with pulmonary embolism in whom temporary and permanent inferior vena cava filters were implanted. The decision process is discussed in relation to the current literature.
Background Celiac plexus neurolysis for the palliative reduction of pain in unresectable pancreatic carcinoma (PC) is safe but provides limited relief. In a previous study, we found that EUS-guided implantation of iodine-125 (125I) around the celiac ganglia is a safe procedure and can induce apoptosis of local neurons in a porcine model. Objective To evaluate the safety and efficacy of direct celiac ganglion irradiation with 125I seeds for the relief of moderate to severe pain secondary to unresectable PC. Design Prospective study. Setting Single, tertiary care referral center. Patients This study enrolled consecutive patients who had moderate to severe pain resulting from biopsy-proven unresectable PC. Intervention All patients underwent EUS-guided direct celiac ganglion irradiation with ...
Calculating prescription doses for new sources by biologically effective dose matching
PurposeIn current clinical practice, single isotopes, such as 125I or 103Pd, are used as single sources in prostate seed implants. A mixture of two radionuclides in the seeds has been proposed for prostate cancer treatment. This study investigates a method for determining the prescription dose for these new seeds using the biological effective dose (BED). MethodsTen prostate cancer cases previously treated using single radionuclide seeds were selected for this study. The BED distribution for these cases was calculated. Plans using other radionuclides were then calculated based on this BED distribution. Prescription values could then be obtained for the calculated plans. The method was verified by calculating the prescription dose for 103Pd and 125I and comparing to clinical values. The met...
Risk for Permanent Pacemaker After Transcatheter Aortic Valve Implantation. Background: Permanent pacemaker (PM) requirement is a known complication after transcatheter aortic valve implantation (TAVI). There are, however, no systematic data concerning this complication. Objective: To determine the incidence and potential predictors of permanent PM requirement after TAVI based on published literature. Methods: We conducted a MEDLINE search to identify potentially relevant literature dealing with PM requirement after TAVI. Data were collected on paper extraction forms by 2 independent investigators. Results: There were 32 relevant published studies comprising data of 5,258 patients without an implanted PM before TAVI. An Edwards-Sapiens prosthesis (ESP) was implanted in 2,887 patients, wher...
Objectives This study sought to define contemporary trends in permanent pacemaker use by analyzing a large national database. Background The Medicare National Coverage Determination for permanent pacemaker, which emphasized single-chamber pacing, has not changed significantly since 1985. We sought to define contemporary trends in permanent pacemaker use by analyzing a large national database. Methods We queried the Nationwide Inpatient Sample to identify permanent pacemaker implants between 1993 and 2009 using the International Classification of Diseases-Ninth Revision-Clinical Modification procedure codes for dual-chamber (DDD), single-ventricular (VVI), single-atrial (AAI), or biventricular (BiV) devices. Annual permanent pacemaker implantation rates and patient demographics were analyze...
Hemocompatibility investigation of the NiTi alloy implanted with tantalum
A composite TiO2/Ta2O5 nano-film has been formed on the NiTi shape memory alloy by Ta implantation. The wettability, protein adsorption, platelets adhesion and hemolysis tests are conducted to evaluate the hemocompatibility. The contact angle measurements showed that the surface of the NiTi alloy kept hydrophilic before and after Ta implantation, although the water contact angle increased with the increasing of implantation current. Both of the surface energy and the interfacial tension decreased after Ta implantation. The protein adsorption behavior was investigated by 125I isotope labeling. The fibrinogen adsorption was enhanced by a high surface roughness or a large interfacial tension, while the albumin adsorption was insensitive to the surface modification. Platelet adhesion and activ...
Vicryl carrier for I-125 seeds: percutaneous transperineal insertion
The use of vicryl carriers for permanent iodine-125 implantation in the prostate with the percutaneous transperineal template technique improves the symmetry of the implant and prevents seed loss into the pelvis. The procedure is accomplished quickly with the administration of spinal or general anesthesia. Implantation into the prostate is accomplished without celiotomy and does not require the use of an iodine seed gun.
Purpose: To update the Allegheny General Hospital experience of high-risk Stage I non-small-cell lung cancer patients treated with sublobar resection and intraoperative {sup 125}I Vicryl mesh brachytherapy. Methods and Materials: Between January 5, 1996 and February 19, 2008, 145 patients with Stage I non-small-cell lung cancer who were not lobectomy candidates because of cardiopulmonary compromise underwent sublobar resection and placement of {sup 125}I seeds along the resection line. The {sup 125}I seeds embedded in Vicryl suture were attached with surgical clips to a sheet of Vicryl mesh, inserted over the target area, and prescribed to a 0.5-cm planar margin. Results: The mean target area, total activity, number of seeds implanted, and prescribed total dose was 33.3 cm{sup 2} (range, 18.0-100.8), 20.2 mCi (range, 11.1-29.7), 46 (range, 30-100), and 117 Gy (range, 80-180), respectively. The median length of the surgical stay was 6 days (range, 1-111), with a perioperative mortality rate of 3.4%. At a median follow-up of 38.3 months (range, 1-133), 6 patients had developed local recurrence (4.1%), 9 had developed regional failure (6.2%), and 25 had distant failure (17.2%). On multivariate analysis, no patient- or tumor-specific factors or surgical or dosimetric factors were predictive of local recurrence. The overall median survival was 30.5 months with a 3- and 5-year overall survival rate of 65% and 35%, respectively. Conclusion: {sup 125}I brachytherapy for high-risk, Stage I non-small-cell lung cancer after sublobar resection is well tolerated and associated with a low local failure rate.
Long-term potency preservation following brachytherapy for prostate cancer
OBJECTIVES -- To assess potency preservation in men following brachytherapy for prostate cancer with or without external beam radiation therapy (EBRT) and/or androgen deprivation therapy (ADT). -- To evaluate the factors that significantly impact this rate. PATIENTS AND METHODS -- In all, 1063 potent men with T1-T3 prostate cancer were treated from 1990 to 2007 with seed implantation alone (103Pd or 125I) (69.6%) or combined modality treatment consisting of a partial dose 103Pd implant followed 6-8 weeks later by EBRT (45-Gy, prostate/seminal vesicles only) (30.4%). ADT was used in 49.1% of cases (range 1-27 months). -- Patients were required to have a minimum of 2 years follow-up and to be off ADT for a minimum of 1 year. -- Erectile function was assessed prior to seed implantation and at...
Interstitially implanted I125 for prostate cancer using transrectal ultrasound
Prostate cancer is the third leading cause of death from cancer among men in the United States. Traditional treatments for prostate cancer are prostatectomy, external beam irradiation, and interstitial implantation of Iodine125 (I125) via laparotomy. These treatments are associated with significant morbidity and limitations. Based on experience with I125 interstitial implantation by transrectal ultrasound guidance for early-stage prostate cancer, it seems that this newer method of treatment has greater accuracy of placement and distribution of the isotope and has had few reported complications. The need for a surgical incision has been eliminated. Hospitalization time also has been decreased, creating the need for ambulatory and inpatient nurses to understand the importance of their respective roles in providing coordinated quality care for these patients. Nurses in these departments must have knowledge of the procedure, radiation safety, and common side effects related to the implant.
A platelet derived growth factor delivery system for bone regeneration
platelet derived growth factor (PDGF) was formulated in a calcium phosphate/biodegradable polymer system for local and controlled delivery to enhance bone regeneration. Implants with a porosity of 67 %, composed of hydroxyapatite, PLGA microspheres and Pluronic®, were obtained by compression. An increase in porosity with time was expected due to Pluronic® dissolution and PLGA microsphere degradation. In vivo PDGF release and tissue distribution were monitored after system implantation into femurs of rabbits using 125I-PDGF. Most of the PDGF was released within approximately 5 days and remained located around the implantation site with negligible systemic exposure. Compared with the reference groups, an important enhancement of bone regeneration was found with doses of 600 and 1,200 ng...
PurposeTo compare the ability of single- and dual-isotope prostate seed implants to escalate biologically effective dose (BED) to foci of disease while reducing prescription dose to the prostate. Methods and MaterialsNine plans, using 125I, 103Pd, and 131Cs alone and in combination were created retrospectively for 2 patients. Ultrasound and MRI/MRS datasets were used for treatment planning. Voxel-by-voxel BED was calculated for single- and dual-isotope plans. Equivalent uniform BED (EUBED) was used to compare plans. The MRS-positive planning target volumes (PTVi) were delineated along with PTV (prostate + 5 mm), rectum, and urethra. Single-isotope implants, prescribed to conventional doses, were generated to achieve good PTV coverage. The PTVi were prospectively used to generate implants u...
BACKGROUND. Brachytherapy is useful for the reirradiation of nasopharyngeal carcinoma. In the current study, the long term treatment results of permanent radioactive gold198 grain interstitial implantation in patients with persistent and recurrent nasopharyngeal carcinoma were reviewed. METHODS. Gol...
Purpose To describe the biochemical failure-free survival (B.F.F.S.), G.U. toxicity and erectile dysfunction in intermediate risk prostate cancer treated with iodine 125 mono-therapy ({sup 125}I). Patients and methods Between October 1994 and October 2007, 1282 patients were treated with {sup 125}I at the Hotel Dieu de Quebec. Two hundred patients were intermediate risk prostate cancer. One hundred and fifty-seven had enough follow-up to be evaluated in this study. Biochemical failure-free survival is reported using Phoenix definition. Acute and late G.U. toxicity was described using the International Prostate Symptoms Score (I.P.S.S.) as well as with the rate of bladder catheter. Erectile dysfunction was also reported. Results The mean age of the patients was 65.6 years (S.D. = 6 years) and the mean pretreatment P.S.A. was 8.7 ng/ml. About half of the patients (51%) were T2b/T2c. About 44.6% had a P.S.A. greater than 10 and 4.5% had Gleason score of 7/10. More than half of the patients received a short course of hormones of less than 6 months for cyto-reduction (57.4%). The median follow-up was 60 months. Biochemical failure-free survival at 60-month and 96-month were 87.1% and 81% according to Phoenix definition. The mean I.P.S.S. rose from 5 immediately after the implant to 15 1 month after and then slowly decreased to 8 at 24 months. Acute urinary retention with bladder catheter occurred in 10.9% of patients. Only 4.3% presented erectile dysfunction at 5 months post-implant. Conclusion {sup 125}I mono-therapy for intermediate risk prostate implant gives biochemical failure-free survivals at 5 years and 8 years comparable to those obtained with high dose external beam radiotherapy. G.U. toxicity and erectile dysfunction were low and acceptable. Therefore, the use of {sup 125}I alone in this group of patients could be presented and discussed with the patient in the waiting of phase III validation. (authors)
Interferon-tau (IFN?), produced by the trophectoderm of ruminant ungulates, binds to the type I IFN receptor (IFNAR) located at the uterine endometrium in a paracrine manner. Since IFN? attenuates the secretory pattern of an endometrial luteolysin, prostaglandin F2?, IFN? has been considered as a conceptus factor implicated in the process of maternal recognition of pregnancy. Here we report the presence of IFNAR subunit (IFNAR1) in ovine conceptuses during the period of peri-implantation development and demonstrate that 125I-human (h) IFN? binds to membrane preparations from ovine corpus luteum and conceptus. Using an antibody against hIFNAR1, immunohistochemical analysis revealed that IFNAR1 protein was present in day 14 and 16 conceptuses (day 0=day of estrus) and luminal and glandular epithelia of the endometrium. Conceptus membrane proteins analyzed by western blot with the same antibody displayed immunoreactive bands at 95, 60 and 55 kDa while endometrial membrane proteins showed bands at 200, 95 and 55 kDa. Northern blot analysis revealed that IFNAR1 mRNA was present in days 15-19 conceptuses and day 18-19 allantoic membranes. Receptor binding studies indicated that 125I-hIFN? binding to day 16, but not earlier, conceptus membrane proteins could be displaced with hIFN? or ovine IFN?. Based on Scatchard analysis, day 16 conceptus membranes contained 28 fmol IFNAR/mg protein with a dissociation constant of 300 pM. Cross-linking experiments demonstrated that 125I-hIFN?-receptor complex migrated at 120 kDa, indicating that the receptor component(s) was approximately 100 kDa. These data provide evidence that although the binding does not occur until day 16, ovine conceptuses possess IFNAR1 near or at the time of implantation, suggesting that IFN?, a factor produced by the trophectoderm of ruminant ungulates, could act on the conceptus in an autocrine manner. In addition to functioning as an antiluteolytic factor, therefore, IFN? may have a direct effect on conceptus development.
The extent of gene delivery and expression in gene therapy with suicide genes such as herpes simplex virus thymidine kinase (HSV-tk) is assessed with measurement of selective localization of radioiodinated HSV-tk substrates in HSV-tk expressing tumor. We compared n vitro uptake of {sup 125}I-IVDU, IVFRU and in vivo image of HSV-tk gene tranduced hepatocellular carcinoma model. Using H{sub 2}O{sub 2}(hydrogen peroxide), IVDU and IVFRU was radiolabeled as carrier free form. The uptake of {sup 125}I-IVDU IVFRU was determined with increasing incubation periods in MCA-tk and MCA cell line (1X10{sup 6}cell/flask). The cell harvested and counted after incubation of 15, 30, 60, 120, 240, 480 minutes. For estimating accumulation of radiolabelled IVDU, IVFRU in HSV-tk expressing tumor, MCA-tk cells (1 X 10{sup 6}/100 {mu}l) injected intramuscularly into right thigh of buffalo rats. To determine selective localization of radiolabelled IVDU, IVFRU in HSV-tk expressing hepatocellular carcinoma bearing buffalo rats, MCA-tk cells (1X 10{sup 7} cell/100 {mu}l) were injected subcutaneously into both shoulders of buffalo rats. Established tumor mass implanted into liver of buffalo rats using intra-hepatic tumor injection. Two weeks later, {sup 123}I labelled IVDU, IVFRU(7.4 X 10{sup 7}Bq/200 {mu}l) injected intravenously into tail veins of each buffalo rats. Gamma camera used as revealing localization of {sup 123}I-IVDU, IVFRU in MCA-tk cells grafts rats and in vivo image was taken 2 hrs, 24 hrs after injection. radioiodinated IVDU, IVFRU were radiolabeled with {sup 123}I as labeling yield 70%, {sup 125}I as 84%. Two compounds showed minimal uptake in MCA cell line, but in MCA-tk cell line, increased uptake was observed. The ratio of MCA-tk to MCA was up to 116-fold in {sup 125}I-IVDU, up to 37-fold in {sup 125}I-IVFRU at 480 min. The uptake of IVDU was 4 times higher than IVFRU in MCA-tk cells. Gamma camera images of HSV-tk gene tranduced MCA tumor showed accumulation of {sup 123}I-IVDU and {sup 123}I-IVFRU to clearly defined images. In hepatocellular carcinoma bearing buffalo rats, selective localization of {sup 123}I-IVFRU observed. Both compound could be used in imaging HSV-tk gene expression for gene therapy monitoring in MCA-tk tumor model. In HSV-tk tranduced hepatocellular carcinoma bearing buffalo rat model, IVFRU could be used as prognostic marker.
OBJECTIVE: The aim of this study was try to find a new way with high precision to implant (125)I-radioactive particles for safe and effective control of tumors that have invaded into the cranial base and orbital regions. STUDY DESIGN: Eight patients with invasive adenoid cystic carcinoma of the cranial base and orbital apex and a history of multiple surgeries were selected. A preoperative magnetic resonance scan was performed and the Brainlab surgical navigation system was used to aid the surgery. RESULTS: The radioactive particles were distributed evenly within the tissue and accurately positioned. No intracranial injury or visual impairment occurred, and the treatment was effective. CONCLUSIONS: The implantation of radioactive particles with the use of magnetic resonance imaging guidance is an effective and safe method for treating invasive malignancies of the skull base and orbital apex, and it should be considered for conditional use. PMID:22858017
Versatile permanent planar implant technique utilizing Iodine-125 seeds imbedded in gelfoam
Tumors attached or adjacent to critical structures can often not be completely resected or resected with adequate surgical margins. Sites involving major blood vessels, the vertebral column or the brain with small residual tumors or suspicious margins often present technical difficulties for standard I-125 or Ir-192 implants. A relatively simple, accurate and inexpensive implant method is decribed using I-125 seeds imbedded in gelfoam to implant permanently into small residual tumors or suspicious margins where standard implant techniques may be unsatisfactory. A method for planning the treatment dose for such an implant is described. Cases involving paraspinal and brain tumors are reported to illustrate the technique.
Objectives Analysis of timing, type, electrocardiographic and patient characteristics of postinterventional bradyarrhythmias after CoreValve implantation. Background Transcatheter aortic valve implantation (TAVI) has become an accepted alternative to surgical therapy in patients with high risk. Among the major drawbacks of this procedure is the need for postprocedural permanent pacemaker implantation (PPM). Although predictors for the postinterventional need for PPM are increasingly recognized, thresholds and rates may vary between centers. Methods We conducted a retrospective single-center analysis in 130 consecutive patients with successful transfemoral CoreValve implantation without preexisting pacemaker implants. Results Postprocedural bradyarrhythmias occurred in 36.2% post-TAVI. Comp...
Biochemical and biological properties of the nerve growth factor receptor
We have utilized a monoclonal antibody (192-IgG) to study the rat nerve growth factor receptor. After intraocular injection, {sup 125}I-192-IgG was retrogradely transported in sympathetic neuronal axons to the superior cervical ganglion. When the sciatic nerve was ligated to induce the accumulation of axonally transported materials, 192-IgG immunostaining was observed on both sides of the ligature, indicating that NGF receptors are transported in both orthograde and retrograde directions. By using {sup 125}I-NGF crosslinking and 192-IgG immunoprecipitation, we detected receptor molecules throughout the rat brain, thereby supporting the hypothesis that NGF is active in the central nervous system. We also discovered that sciatic nerve transection leads to a dramatic increase in the amount of NGF receptor found in the distal portion of the nerve. Immunostaining revealed that all Schwann cells in the distal axotomized nerve were expressing NGF receptors. We examined phosphorylation of NGF receptor in cultured sympathetic neurons and PC12 cells. We also examined pharmacological effects of 192-IgG. Systemic injection of 192-IgG into neonatal rats caused a permanent partial sympathectomy in a dose-dependent manner; a maximum of 50% of the cells were killed.
A problem faced by all Monte Carlo (MC) particle transport codes is how to handle overlapping geometries. The Geant4 MC toolkit allows the user to create parallel geometries within a single application. In Geant4 the standard mass-containing geometry is defined in a simulation volume called the World Volume. Separate parallel geometries can be defined in parallel worlds, that is, alternate three dimensional simulation volumes that share the same coordinate system with the World Volume for geometrical event biasing, scoring of radiation interactions, and/or the creation of hits in detailed readout structures. Until recently, only one of those worlds could contain mass so these parallel worlds provided no solution to simplify a complex geometric overlay issue in brachytherapy, namely the overlap of radiation sources and applicators with a CT based patient geometry. The standard method to handle seed and applicator overlay in MC requires removing CT voxels whose boundaries would intersect sources, placing the sources into the resulting void and then backfilling the remaining space of the void with a relevant material. The backfilling process may degrade the accuracy of patient representation, and the geometrical complexity of the technique precludes using fast and memory-efficient coding techniques that have been developed for regular voxel geometries. The patient must be represented by the less memory and CPU-efficient Geant4 voxel placement technique, G4PVPlacement, rather than the more efficient G4NestedParameterization (G4NestedParam). We introduce for the first time a Geant4 feature developed to solve this issue: Layered Mass Geometry (LMG) whereby both the standard (CT based patient geometry) and the parallel world (seeds and applicators) may now have mass. For any area where mass is present in the parallel world, the parallel mass is used. Elsewhere, the mass of the standard world is used. With LMG the user no longer needs to remove patient CT voxels that would include for example seeds. The patient representation can be a regular voxel grid, conducive to G4NestedParam, and the patient CT derived materials remain exact, avoiding the inaccuracy of the backfilling technique. Post-implant dosimetry for one patient with 125I permanent seed implant was performed using Geant4 version 9.5.p01 using three different geometrical techniques. The first technique was the standard described above (G4PVPlacement). The second technique placed patient voxels as before, but placed seeds with LMG (G4PVPlacement+LMG). The third technique placed patient voxels through G4NestedParam and seeds through LMG (G4NestedParam+LMG). All the scenarios were calculated with 3 different image compression factors to manipulate the number of voxels. Additionally, the dosimetric impact of the backfilling technique was investigated for the case of calcifications in close proximity of sources. LMG eliminated the need for backfilling and simplified geometry description. Of the two LMG techniques, G4PVPlacement+LMG had no benefit to calculation time or memory use, actually increasing calculation time, but G4NestedParam+LMG reduced both calculation time and memory. The benefits of G4NestedParam+LMG over standard G4PVPlacement increased with increasing voxel numbers. For the case of calcifications in close proximity to sources, LMG not only increased efficiency but also yielded more accurate dose calculation than G4PVPlacement. G4NestedParam in combination with LMG present a new, efficient approach to simulate radiation sources that overlap patient geometry. Cases with brachytherapy applicators would constitute a direct extension of the method.
The long-term results of the management of metastatic renal cell carcinoma by a radioactive interstitial implant seated by a transcatheter embolization technique were evaluated in 85 patients at risk at 2 years and 37 at 5 years. The 2-year survival rate was 33% and the 5-year survival rate was 32%. Patients with isolated skeletal metastases showed the best survival rate (2-year survival rate, 69%; 5-year survival rate, 60%). Isolated pulmonary, other parenchymal, and central nervous system (CNS) metastases showed a lower 2-year survival rate of 15%. Regardless of the site of metastases and the size of the primary, histologic grade appeared to have a substantial impact on the survival of our patients. The beneficial results of interstitial radiation therapy are attributed to reduction of tumor burden and possibly the stimulation of the host immune response that may initiate remission. The noticeably better results in patients with osseous metastases are attributed to the resolute treatment of all osseous metastases by additional interstitial iodine 125 (/sup 125/I) infarct implants. Conversely, the poor results in patients with CNS and other parenchymal metastases may be based on the inability to treat such metastases with /sup 125/I interstitial infarct implants. In addition to clinical observations of weight gain and the cessation of pain and hematuria if present, remissions are heralded by normalization of the erythrocyte sedimentation rate, disappearance of tumor markers if present, and rise of beta interferon levels. The technique is advocated for the management of inoperable renal cell carcinoma with distant metastases.
A Monte Carlo study is carried out to quantify the effects of seed anisotropy and interseed attenuation for 103Pd and 125I prostate implants. Two idealized and two real prostate implants are considered. Full Monte Carlo simulation (FMCS) of implants (seeds are physically and simultaneously simulated) is compared with isotropic point-source dose-kernel superposition (PSKS) and line-source dose-kernel superposition (LSKS) methods. For clinical pre- and post-procedure implants, the dose to the different structures (prostate, rectum wall, and urethra) is calculated. The discretized volumes of these structures are reconstructed using transrectal ultrasound contours. Local dose differences (PSKS versus FMCS and LSKS versus FMCS) are investigated. The dose contributions from primary versus scattered photons are calculated separately. For 103Pd, the average absolute total dose difference between FMCS and PSKS can be as high as 7.4% for the idealized model and 6.1% for the clinical preprocedure implant. Similarly, the total dose difference is lower for the case of 125I: 4.4% for the idealized model and 4.6% for a clinical post-procedure implant. Average absolute dose differences between LSKS and FMCS are less significant for both seed models: 3 to 3.6% for the idealized models and 2.9 to 3.2% for the clinical plans. Dose differences between PSKS and FMCS are due to the absence of both seed anisotropy and interseed attenuation modeling in the PSKS approach. LSKS accounts for seed anisotropy but not for the interseed effect, leading to systematically overestimated dose values in comparison with the more accurate FMCS method. For both idealized and clinical implants the dose from scattered photons represent less than 1/3 of the total dose. For all studied cases, LSKS prostate DVHs overestimate D90 by 2 to 5% because of the missing interseed attenuation effect. PSKS and LSKS predictions of V150 and V200 are overestimated by up to 9% in comparison with the FMCS results. Finally, effects of seed anisotropy and interseed attenuation must be viewed in the context of other significant sources of dose uncertainty, namely seed orientation, source misplacement, prostate morphological changes and tissue heterogeneity. PMID:16193786
A Monte Carlo study is carried out to quantify the effects of seed anisotropy and interseed attenuation for {sup 103}Pd and {sup 125}I prostate implants. Two idealized and two real prostate implants are considered. Full Monte Carlo simulation (FMCS) of implants (seeds are physically and simultaneously simulated) is compared with isotropic point-source dose-kernel superposition (PSKS) and line-source dose-kernel superposition (LSKS) methods. For clinical pre- and post-procedure implants, the dose to the different structures (prostate, rectum wall, and urethra) is calculated. The discretized volumes of these structures are reconstructed using transrectal ultrasound contours. Local dose differences (PSKS versus FMCS and LSKS versus FMCS) are investigated. The dose contributions from primary versus scattered photons are calculated separately. For {sup 103}Pd, the average absolute total dose difference between FMCS and PSKS can be as high as 7.4% for the idealized model and 6.1% for the clinical preprocedure implant. Similarly, the total dose difference is lower for the case of {sup 125}I: 4.4% for the idealized model and 4.6% for a clinical post-procedure implant. Average absolute dose differences between LSKS and FMCS are less significant for both seed models: 3 to 3.6% for the idealized models and 2.9 to 3.2% for the clinical plans. Dose differences between PSKS and FMCS are due to the absence of both seed anisotropy and interseed attenuation modeling in the PSKS approach. LSKS accounts for seed anisotropy but not for the interseed effect, leading to systematically overestimated dose values in comparison with the more accurate FMCS method. For both idealized and clinical implants the dose from scattered photons represent less than 1/3 of the total dose. For all studied cases, LSKS prostate DVHs overestimate D{sub 90} by 2 to 5% because of the missing interseed attenuation effect. PSKS and LSKS predictions of V{sub 150} and V{sub 200} are overestimated by up to 9% in comparison with the FMCS results. Finally, effects of seed anisotropy and interseed attenuation must be viewed in the context of other significant sources of dose uncertainty, namely seed orientation, source misplacement, prostate morphological changes and tissue heterogeneity.
Serum half life, tissue uptake and urinary excretion of N-terminal truncated IGF variants and their intact precursors were compared to see whether the variants regulate the bioavailability of those growth factors. IGF-I, des(1-3) IGF-I, IGF-II and des(1-6) IGF-II were labeled with {sup 125}I and intravenously administered to SD rats. Blood from femoral artery and urine from implanted bladder catheter were collected at appropriate intervals until sacrifice of animals at 2 hr after administration. Tissues were dissected out and all of these samples were measured for their radioactivity with a gamma counter. The half lives of des(1-3) IGF-I, IGF-I, des(1-6) IGF-II and IGF-II were 20.5, 228.3, 21.3 and 181.7 min, respectively. Maximal accumulation of all peptides was found in the kidney. {sup 125}I-IGF-I and -II showed the following distribution pattern; levels were higher in the kidney>pancreas>small intestine>liver>duodenum>stomach>lung>spleen>heart>large intestine>testis>brain>skeletal muscle. Skeletal muscle, kidney and testis showed a preferential uptake of the variants. Urinary excretion of the variants were much greater. Thus the variants were more rapidly cleared from circulation. The physiological significance of tissue distribution of 4 peptides remains to be further investigated. (K.H.)
Glucagon degradation by a product of the Walker 256 carcinosarcoma
Male Sprague-Dawley rats (125-150g) were implanted (im.) with the Walker 256 carcinosarcoma. After both 7 and 10 days, plasma levels of glucagon in tumor-bearing rats were approximately half the level seen in control rats (P < 0.01) even though fasting plasma glucose levels were slightly (but not significantly) less in the tumor-bearing rats. To determine if the tumor degrades the hormone, tumor cells were incubated at room temperature with /sup 125/I-glucagon (0.075 ..mu..Ci, 2200 Ci/mmol) in 20mM TRIS-HCl buffer (pH 7.4) with 2.5% bovine serum albumin (total volume of 750 ..mu..l) for 45 min. After incubation with tumor cells, only about 25% of the total radiolabel was TCA-precipitable vs 97% in the control (minus tumor cells) incubations. It also appears that the tumor cells may release a substance which degrades hormone. If tumor cells are preincubated for 60 min at 37/sup 0/ then removed from the medium, the incubation medium contains a factor which degrades subsequently added /sup 125/I-glucagon (57% TCA-precipitable vs 98% in control incubations). That this factor is a protease is suggested by the results of another experiment in which aprotinin (a protease inhibitor, 1 mg/ml), when added along with the labeled glucagon, virtually eliminated degradation by a factor released from the tumor cells (79% TCA-precipitable in the absence of aprotinin vs 94% in its presence and 98% in controls).
Introduction. High expression of the system L amino acid transporter has been observed in clinically important tissues including tumors and the blood-brain barrier. We examined amino acid transport system L selectivity of 14C(U)-l-tyrosine (14C-Tyr), 125I-4-iodo-l-meta-tyrosine (4-125I-mTyr), 125I-6-iodo-l-meta-tyrosine (6-125I-mTyr), 125I-3-iodo-?-methyl-l-tyrosine (125I-IMT) and 125I-3-iodo-l-tyrosine (3-125I-Tyr) using Chinese hamster ovary cells (CHO-K1).Methods. Cells in the exponential growth phase were incubated with 18.5 kBq of labeled amino acid in 2 mL of phosphate-buffered saline-based uptake solution and an uptake solution with/without Na+ at 37?C or 4?C. We examined the effects of the following compounds (1.0 mM) on transport: 2-(methylamino)isobutyric acid (a specific inhibit...
Abstract in portuguese É relatado caso de paciente de 82 anos, portador de insuficiência renal leve, estenose valvar pulmonar (EVP) severa, estenose severa de artéria descendente anterior e bloqueio atrioventricular total, submetido a angioplastia coronária com implante de stent coronário, valvotomia pulmonar e implante de marcapasso definitivo no mesmo procedimento, com sucesso. Abstract in english This report describes a case involving an 82 year old patient with mild renal insufficiency, severe pulmonary valve stenosis (PVS), severe anterior descending artery stenosis and complete atrioventricular block, who successfully underwent, in a single session, coronary angioplasty and a stent implant, pulmonary valvotomy and a permanent pacemaker implant.
Purified recombinant human gamma interferon (HuIFN-gamma), labeled with 125I (125I-HuIFN-gamma), was used to study receptors for HuIFN-gamma on human WISH cells. 125I-HuIFN-gamma was bound to WISH cells, and this binding was displaced by unlabeled HuIFN-gamma but not by unlabeled recombinant HuIFN-a...
Albumin permeation of new vessels is increased in diabetic rats
/sup 125/I-bovine serum albumin (BSA) permeation of the vasculature of 3-wk-old granulation tissue (induced by subcutaneous implantation of polyester fabric) formed in the diabetic milieu was assessed in female BB/W, spontaneously diabetic rats and in male, Sprague-Dawley rats with streptozocin-induced diabetes as well as in corresponding nondiabetic controls. Albumin permeation of new granulation tissue vessels was markedly increased in both groups of diabetic animals relative to that of nondiabetic controls, while albumin permeation of vessels in most other tissues did not differ for controls and diabetics. These observations indicate that the functional integrity of new vessels formed in the diabetic milieu is impaired: (1) to a greater extent than that of older vessels formed before induction of diabetes and (2) relative to new vessels in nondiabetics. The implication of these observations is that molecular constituents of vessels synthesized in the diabetic milieu are quantitatively and/or qualitatively abnormal and/or their incorporation into vessels is defective.
Gestational exposure to nicotine has been shown to affect development of noradrenergic activity in both the central and peripheral nervous systems. In the current study, pregnant rats received nicotine infusions of 6 mg/kg/day throughout gestation, administered by osmotic minipump implants. After birth, offspring of the nicotine-infused dams exhibited marked increases in basal adenylate cyclase activity in membranes prepared from kidney and heart, as well as supersensitivity to stimulation by either a {beta}-adrenergic agonist, isoproterenol, or by forskolin. The altered responses were not accompanied by up-regulation of {beta}-adrenergic receptors: in fact, ({sup 125}I)pindolol binding was significantly decreased in the nicotine group. These results indicate that fetal nicotine exposure affects enzymes involved in membrane receptor signal transduction, leading to altered responsiveness independently of changes at the receptor level.
PurposeThe 125I source currently used for prostate brachytherapy at St. James’s Institute of Oncology is a standard size seed (4.5mm in length and 0.8mm in diameter). A new, thinner seed is under evaluation. This is designed to be implanted using narrower needles, potentially reducing edema and improving the dose distribution. This study investigated the visibility of the thinner source on multimodality images and compared it with that of standard size seeds. Methods and MaterialsImages of dummy seeds of both thinner and standard size models were taken using ultrasound, fluoroscopy, computed tomography (CT), and magnetic resonance (MR) imaging. The ultrasound, fluoroscopy, and CT images were acquired with the seeds inserted into phantoms positioned in a water tank. The MR images wer...
We have reported that Pisum sativum agglutinin (PSA), a plant lectin which recognizes mannosyl residues, accumulates markedly in Ehrlich solid tumor (EST) and suggested the possibility of applying PSA to tumor imaging radiopharmaceuticals. In the present work, an inflammation was induced by implantation of cotton thread in the left rear leg skeletal muscle of ddY mice and Ehrlich ascites tumor cells were inoculated into the right rear leg. /sup 67/Ga-citrate accumulated in the tumor tissue and the inflammatory lesion to almost equal extents. On the other hand, /sup 125/I-PSA preferentially accumulated in tumor tissues in mice bearing both tumor and inflammation. The results suggest that differential diagnosis of tumor from inflammation using radiolabeled PSA may be possible.
A multidisciplinary approach for the management of hypodontia: case report
Abstract in english Hypodontia is the congenital absence of one or more teeth and may affect permanent teeth. Several options are indicated to treat hypodontia, including the maintenance of primary teeth or space redistribution for restorative treatment with partial adhesive bridges, tooth transplantation, and implants. However, a multidisciplinary approach is the most important requirement for the ideal treatment of hypodontia. This paper describes a multidisciplinary treatment plan for con (more) genitally missing permanent mandibular second premolars involving orthodontics, implantology and prosthodontic specialties.
Purification of /sup 125/I-vasoactive intestinal peptide by reverse-phase HPLC
VIP was labeled with sodium (/sup 125/I)iodide, and /sup 125/I-VIP was purified by reverse-phase high performance liquid chromatography. Optimal separations of /sup 125/I-VIP and unlabeled VIP were obtained using two C18- Novapak columns in series and a gradient of acetonitrile in triethylamine phosphate for elution. The specific activity of the /sup 125/I-VIP was 1.99 +/- 0.21 Ci/mumole, approaching the maximum specific activity of monoiodinated VIP (2.26 Ci/mumole). Radioimmunoassay and radioreceptorassay for VIP were more sensitive (2.6-fold, and 2.5-fold, respectively) using /sup 125/I-VIP purified by HPLC compared to /sup 125/I-VIP obtained from an open-end cellulose column. These results demonstrate the advantage of preparing purified /sup 125/I-VIP by HPLC for the accurate assay of VIP and VIP-receptors in tissues and biological fluids.
We have used compartmented cultures of rat sympathetic neurons to quantitatively examine the retrograde transport of 125I-nerve growth factor (NGF) supplied to distal axons and to characterize the cellular events that maintain steady-state levels of NGF in cell bodies. In cultures allowed to reach steady-state 125I-NGF transport, cell bodies contained only 5-30% of the total neuron-associated 125I-NGF, whereas 70-95% remained associated with the distal axons. This was true over an 8 pM to 1.5 nM 125I-NGF concentration range, indicating that saturation of high affinity receptors could not account for the large fraction of 125I-NGF remaining in axons. Dissociation assays indicated that 85% of 125I-NGF associated with distal axons was surface-bound. At steady-state, only 2-25% of the distal axon-associated 125I-NGF was retrogradely transported each hour, with higher transport rates associated with younger cultures and lower 125I-NGF concentrations. The velocity of 125I-NGF retrograde transport was estimated at 10-20 mm/hr. However, as in a previous report, almost no 125I-NGF transport was observed during the first hour after 125I-NGF administration, indicating a significant lag between receptor binding and loading onto the retrograde transport system. During 125I-NGF transport through axons spanning an intermediate compartment in five-compartment cultures, little or no 125I-NGF was degraded or released from the axons. After transport, 125I-NGF was degraded with a half-life of 3 hr. In summary, although some cellular events promoted NGF accumulation in cell bodies, distal axons represented by far the principal site of NGF-receptor interaction at steady-state as a result of a low retrograde transport rate. PMID:9006972
Forskolin photoaffinity labels with specificity for adenylyl cyclase and the glucose transporter
Two photolabels, N-(3-(4-azido-3-125I-phenyl)-propionamide)-6- aminoethylcarbamylforskolin(125I-6-AIPP-Fsk) and N-(3-(4-azido-3-125I-phenyl)propionamide)-7-aminoethylcarbamyl-7- desacetylforskolin (125I-7-AIPP-Fsk) were synthesized with specific activities of 2200 Ci/mmol and used to label adenylyl cyclase and the glucose transporter. The affinities of the photolabels for adenylyl cyclase were determined by their inhibition of (3H)forskolin binding to bovine brain membranes. 6-AIPP-Fsk and 7-AIPP-Fsk inhibited (3H)forskolin binding with IC50 values of 15 nM and 200 nM, respectively. 125I-6-AIPP-Fsk labeled a 115-kDa protein in control and GTP {gamma} S-preactivated bovine brain membranes. This labeling was inhibited by forskolin but not by 1,9-dideoxyforskolin or cytochalasin B. 125I-6-AIPP-Fsk labeling of partially purified adenylyl cyclase was inhibited by forskolin but not by 1,9-dideoxyforskolin. 125I-7-AIPP-Fsk specifically labeled a 45-kDa protein and not a 115-kDa protein in control and GTP {gamma} S-preactivated brain membranes. This labeling was inhibited by forskolin, 1,9-dideoxyforskolin, cytochalasin B, and D-glucose but not cytochalasin E or L-glucose. Human erythrocyte membranes were photolyzed with 125I-6-AIPP-Fsk and 125I-7-AIPP-Fsk. 125I-7-AIPP-Fsk, but not 125I-6-AIPP-Fsk, strongly labeled a broad 45-70-kDa band. Forskolin, 7-bromoacetyl-7-desacetylforskolin, 1,9-dideoxyforskolin, cytochalasin B, and D-glucose, but not cytochalasin E or L-glucose, inhibited 125I-7-AIPP-Fsk labeling of the 45-70-kDa band. 125I-6-AIPP-Fsk and 125I-7-AIPP-Fsk are high affinity photolabels with specificity for adenylyl cyclase and the glucose transporter, respectively.
OBJECTIVE: To identify clinical and electrical factors predicting delayed high degree atrio-ventricular block (AVB) after transcatheter aortic valve implantation (TAVI). BACKGROUND: TAVI is a new technique for treating severe aortic valve stenosis in patients at high surgical risk but can be followed by high grade AVB requiring permanent pacing. METHODS AND RESULTS: The study included 79 patients (82±17 years, Euroscore=23±10 %) free of permanent pacing need before and immediately after TAVI procedure. Delayed high degree AVB was defined by type 2 or 3 AVB diagnosed at least 24 hours after the index procedure. Permanent pace maker implantation was performed for all these patients. We compared clinical and electrical variables before and after TAVI in patients with delayed AVB or not. TAVI was performed successfully in all patients. The 21 (26%) patients who exhibited delayed high grade AVB had significantly deeper prosthesis implantation (12±4 mm vs. 9±5 mm, P=0.03) and wider post-TAVI QRS duration (155±17 ms vs. 131±25 ms, P=0.0004), with no difference in baseline QRS duration. Post-TAVI QRS duration was the only independent predictor of post-TAVI permanent for delayed high degree AVB (P=0.02). After a mean follow-up of 10±8 months, all 21 patients with post-TAVI QRS ?128 ms were free of high-grade AVB, while 21/55 (38%) patients with post-TAVI QRS >128 ms had permanent pacing (P=0.0016). CONCLUSION: Delayed ( 24 hours after the procedure) high-grade AVB necessitating permanent pacing is common after TAVI. QRS duration measured immediately after TAVI was the best independent predictor of permanent pacing in this population. Patients with QRS ?128 ms immediately after TAVI had no risk of requiring permanent pacing. © 2012 Wiley Periodicals, Inc. PMID:22972678
Curie-therapy with gamma transmitters; Curietherapie avec emetteurs gamma
This article made it possible to briefly look over the techniques of curie-therapy, the temporary implants with the radium of cancers of the skin to the permanent implants for cancers of the prostate. Curie-therapy has been applied to the temporary implants of the prostate to prevent restenose (closing of an artery after an operation like angioplasty) in the arteries i.e. the intravascular curietherapy. A very significant field of study is the relation between the dosimetry , the improvement of the techniques of dosimetry and the prognostic factors of the treatment (survival, side effects)
Abstract Endocarditis and localized pocket infections are recognized as serious adverse events in patients with implanted cardiac impulse generators. We have undertaken a 10-y retrospective study in North Denmark Region (population 0.5 million) in order to elucidate the clinical spectrum, causative microorganisms, management and outcome. Infections associated with permanent pacemakers (PPM) and implanted cardioverter-defibrillator (ICD) devices were identified by searching hospital databases. Ninety-one incident cases were recorded in 1999 through 2008: 26 patients had endocarditis, 39 patients had a localized pocket infection, and 9 patients developed surgical sepsis with or without local signs immediately after implantation or reoperation; the device was the likely but unconfirmed focus ...
Treatment of prostate cancer by permanent implantation of radioactive seeds is now a good alternative to radical surgery or radiotherapy, as it provides a good tumor control while the risk is reduced by a lower complication irradiation of adjacent healthy organs. The large volume change during seed implantation occurs in the prostate of the patient, makes it important to consider margins around the organs of interest both to ensure optimal coverage and minimal tumor irradiation of healthy tissue. Analyze how the volume varies during and after implantation and establish a margin around the prostate to the practice of our hospital are the two objectives of this work.
Purpose: Surgical trauma-induced edema and its protracted resolution can lead to significant dose reductions in preplanned {sup 131}Cs prostate brachytherapy. The purpose of this work was to examine whether these dose reductions should be actively compensated for and to estimate the magnitude of the additional irradiation needed for dose compensation. Methods and Materials: The quantitative edema resolution characteristics observed by Waterman et al. were used to examine the physical and radiobiologic effects of prostate edema in preplanned {sup 131}Cs implants. The need for dose compensation was assessed using the dose responses observed in {sup 125}I and {sup 103}Pd prostate implants. The biologically effective dose, calculated with full consideration of edema evolution, was used to estimate the additional irradiation needed for dose compensation. Results: We found that the edema-induced dose reduction in preplanned {sup 131}Cs implants could easily exceed 10% of the prescription dose for implants with moderate or large edema. These dose reductions could lead to a >10% reduction in the biochemical recurrence-free survival for individual patients if the effect of edema was ignored. For a prescribed dose of 120 Gy, the number of 2-Gy external beam fractions needed to compensate for a 5%, 10%, 15%, 20%, and 25% edema-induced dose reduction would be one, four, six, seven, and nine, respectively, for prostate cancer with a median potential doubling time of 42 days. The required additional irradiation increased for fast-growing tumors and/or those less efficient in sublethal damage repair. Conclusion: Compensation of edema-induced dose reductions in preplanned {sup 131}Cs prostate brachytherapy should be actively considered for those implants with moderate or large edema.
I-123 metaiodobenzylguanidine cardiac scintigraphy in patients with an implanted permanent pacemaker
Tl scintigraphic abnormalities have been reported in patients with an implanted permanent pacemaker, but little is known about the MIBG scintigraphic findings in such patients. This study was performed to assess the MIBG scintigraphic findings in patients with an implanted permanent pacemaker, and to test the hypothesis that imaging characteristics of MIBG scintigraphy differ according to its mode. Twelve patients (4 men and 8 women, mean age: 72.4{+-}9.5 years), who had undergone the implantation of a permanent pacemaker for bradyarrhythmias, underwent MIBG scintigraphy. The patients were divided into VVI pacemaker and DDD pacemaker groups. The tomograms were divided into nine segments and the MIBG defect in each segment scored on a scale ranging from 0 (normal uptake) to 3 (no uptake). Total MIBG defect scores were generated by summing the scores for the nine segments in each patient. MIBG scintigraphic abnormalities were found in ten of the twelve patients. The six patients with the VVI pacemaker manifested MIBG scintigraphic abnormalities. These MIBG scintigraphic abnormalities were observed in all segments, particularly in the posterior segments. The mean total defect score of the VVI group was higher than that of the DDD group (14.8{+-}9.8 vs 3.0{+-}3.5, respectively p<0.05). Therefore, we conclude that despite several limitations of the study, MIBG scintigraphic abnormalities occur in patients with implanted permanent pacemakers, and that such abnormalities are more prominent with the VVI than DDD pacemaker. (author).
with permanently implanted electrodes in cortical and subcortical structures. .... the trial marked by the first unreinforced failure to respond and the trials that followed. ..... the electrodes carefully, without having to grind away the dental cement, the head .... Water, with an added vitamin supplement, was always available to ...
Low density lipoprotein (LDL) modified by incubation with phospholipase C (PLC-LDL) aggregates in solution and is rapidly taken up and degraded by human and mouse macrophages, producing foam cells in vitro. Human, mouse, and rabbit macrophages degraded {sup 125}I-labeled PLC-LDL ({sup 125}I-PLC-LDL) more rapidly than native {sup 125}I-labeled LDL ({sup 125}I-LDL), while nonphagocytic cells such as human fibroblasts and bovine aortic endothelial cells degraded {sup 125}I-PLC-LDL more slowly than {sup 125}I-LDL. This suggested the mechanism for internalization of PLC-LDL was phagocytosis. When examined by electron microscopy, mouse peritoneal macrophages appeared to be phagocytosing PLC-LDL. The uptake and degradation of {sup 125}I-PLC-LDL by human macrophages was inhibited >80% by the monoclonal antibody C7 (IgG2b) produced by hybridoma C7, which blocks the ligand binding domain of the LDL receptor. Similarly, methylation of {sup 125}I-LDL ({sup 125}I-MeLDL) prior to treatment with phospholipase C decreased its subsequent uptake and degradation by human macrophages by >90%. The uptake and degradation of phospholipase C-modified {sup 125}I-MeLDL by macrophages could be restored by incubation of the methylated lipoprotein with apoprotein E, a ligand recognized by the LDL receptor. These results indicate that macrophages internalize PLC-LDL by LDL receptor-dependent phagocytosis.
Processing and transfer of epidermal growth factor in developing rat jejunum and ileum
Using everted sac technique we demonstrated the transfer of {sup 125}I-mEGF across the jejunal and ileal walls of suckling, weanling and adult rats. The transfer by the suckling rat jejunum and ileum was significantly inhibited by the presence of dinitrophenol and sodium azide or by the replacement of sodium with potassium or choline, RP-HPLC analysis detected carboxy-terminal processing of {sup 125}I-mEGF in suckling and adult rat jejunum and ileum. Suckling rat jejunum produced {sup 125}I-des(53)mEGF and {sup 125}I-des(49-53)mEGF, whereas {sup 125}I-des(48-53)mEGF was detected in suckling rat ileum or adult rat jejunum and ileum. All three forms of {sup 125}I-mEGF bound to anti-EGF antibody and EGF receptors. The receptor binding of {sup 125}I-des(53)mEGF was higher than that of {sup 125}I-mEGF, but those of {sup 125}I-des(49-53)mEGF and {sup 125}I-des(48-53)mEGF were greatly diminished. Results indicate a carboxy-terminal processing of mouse EGF during uptake and transfer in the small intestine of developing and adult rats, and the resulting products showed altered receptor binding. An identical amino acid sequence of the C-terminal pentapeptide of eGF from mouse, human and possibly rat may suggest a biological significance of C-terminal processing of EGF in the small intestine.
Background Subretinal implants aim to replace photoreceptor function in patients suffering from degenerative retinal disease like retinitis pigmentosa by topically applying electrical stimuli in the subretinal space. This study?as a last step before upcoming human trials?explored a newly developed surgical technique for permanent implantation of complex subretinal implants with extra-ocular parts. Methods The implant consisted of a microphotodiode array (MPDA) with 1,550 electrodes and a 4?4 array of gold electrodes for direct electrical stimulation; both were mounted onto a polyimide foil for transscleral placement into the subretinal space. The foil carried connection lanes to a silicone cable that was implanted under the skin and led to a stimulator box in the animal?s neck. Surgery was...
Purpose: The aim of this study was to use permanent seed implants in the breast and describe our experience with 15 cases, using iodine seed implants as a tumor bed boost.Methods and Materials: Breasts were fixed with a thermoplastic sheet, a template bridge applied, the thorax scanned and the images rotated to be perpendicular to the implant axis. Skin, heart, and lung were delineated. A preplan was made, prescribing 50 Gy to the clinical target volume (CTV), consisting in this boost series of nearly a quadrant. Iodine (125) seeds were stereotactically implanted through the template, and results were checked with a postplan computed tomographic (CT) scan.Results: The breast was immobilized reproducibly. Simulation, scanning, and implant were performed without difficulties. Preplan CTV D90...
Predictors of permanent pacemaker implantation after Medtronic CoreValve bioprosthesis implantation
Aims High-grade conduction disturbances requiring permanent pacemaker (PPM) implantation occur in up to 40% of patients following transcatheter aortic valve implantation (TAVI). The aim of this study was to identify pre-operative risk factors for PPM implantation after TAVI with the Medtronic CoreValve prosthesis (CVP). Methods and results We retrospectively analysed 109 patients following transfemoral CVP implantation performed between 2008 and 2009 at the Leipzig Heart Center. Patients who had indwelling PPM at the time of TAVI (n = 21) were excluded, leaving 88 patients for analysis. Mean age was 80.3 ± 6.6 years and logistic EuroScore predicted risk of mortality was 23.3 ± 12.1%. A total of 32 patients (36%) underwent PPM implantation post-TAVI...
PurposeTo study the influence of prostatic edema on postimplant physical and radiobiological parameters using 131Cs permanent prostate seed implants. Methods and MaterialsThirty-one patients with early prostate cancer who underwent 131Cs permanent seed implantation were evaluated. Dose-volume histograms were generated for each set of prostate volumes obtained at preimplantation and postimplantion days 0, 14, and 28 to compute quality indices (QIs) and fractional doses at level x (FDx). A set of equations for QI, FDx, and biologically effective doses at dose level Dx (BEDx) were defined to account for edema changes with time after implant. ResultsThere were statistically significant differences found between QIs of pre- and postimplant plans at day 0, except for the overdose index (ODI). QI...
Objectives The purpose of this study was to evaluate the need for a permanent pacemaker after transcatheter aortic valve implantation with the CoreValve prosthesis (Medtronic, Inc., Minneapolis, Minnesota) using the new Accutrak delivery system (Medtronic, Inc.). Background The need for a permanent pacemaker is a recognized complication after transcatheter aortic valve implantation with the CoreValve prosthesis. Methods Between April 23, 2008 and May 31, 2011, 195 consecutive patients with symptomatic aortic valve stenosis underwent transcatheter aortic valve implantation using the self-expanding CoreValve prosthesis. In 124 patients, the traditional delivery system was used, and in 71 patients, the Accutrak delivery system was used. Results There were no significant differences in baselin...
The role of plasma lipoproteins and hypophyseal hormones in the maintenance of progesterone secretion by the rat corpus luteum was investigated. In the first experiment, rats were treated daily from days 1-6 of pregnancy with 5 mg/kg 4-aminopyrozolopyramidine (4APP), a blocker of hepatic lipoprotein secretion, or with 5 mg/kg 4APP and 1 or 2 mg ovine PRL or 0.1 ml 0.5% phosphoric acid (4APP vehicle). The administration of 4APP reduced serum cholesterol and progesterone levels on days 2-6 of pregnancy and ovarian progesterone on day 6. The reduced progesterone secretion had no effect on embryo implantation. PRL, in the doses used, was incapable of abrogating the effects of 4APP on circulating or ovarian progesterone levels. Ovaries and adrenals, but not kidneys, of pseudopregnant rats exhibited specific and saturable uptake of porcine high density lipoprotein (HDL). Time-course studies indicated that the uptake of HDL was rapid in ovaries compared to that in adrenals. Ovaries from rats not only exhibited uptake of porcine HDL, but also were capable of using it for progesterone synthesis. Treatment with 4APP increased the adrenal uptake of HDL, but ovarian uptake was not different from that in the control group. Hypophysectomy reduced both adrenal and ovarian uptake of HDL. In adrenals only ACTH at the dose employed ameliorated reduction of HDL uptake induced by hypophysectomy, while in the ovaries, both PRL and LH reversed the effect of hypophysectomy. The effect of PRL on uptake was specific to (/sup 125/I)HDL and did not alter (/sup 125/I)albumin uptake. It is concluded that: 1) hypophysectomy reduces HDL uptake in the luteinized rat ovary; and 2) PRL and LH replacement therapy maintain ovarian uptake of HDL, suggesting a direct effect of these luteotropins on lipoprotein uptake.
BACKGROUND Current management of permanent facial paralysis centers on nerve grafting and muscle transfer; however, limitations of those procedures call for other options. OBJECTIVES To determine the durability and biocompatibility of implanted artificial muscle in a gerbil model and the degree of inflammation and fibrosis at the host tissue-artificial muscle interface. METHODS Electroactive polymer artificial muscle (EPAM) devices engineered in medical-grade silicone were implanted subcutaneously in 13 gerbils. The implanted units were stimulated with 1 kV at 1 Hz, 24 h/d via a function generator. Electrical signal input/output was recorded up to 40 days after implantation. The animals were euthanized between 23 and 65 days after implantation, and the host tissue-implant interface was evaluated histologically. RESULTS The animals tolerated implantation of the EPAM devices well, with no perioperative deaths. The muscle devices created motion for a mean of 30.3 days (range, 19-40 days), with a mean of 2.6 × 106 cycles (range, 1.6 × 106 to 3.5 × 106 cycles). Histologic examination of the explanted devices revealed the development of a minimal fibrous capsule surrounding the implants, with no evidence of bacterial infection or inflammatory infiltrate. No evidence of device compromise, corrosion, or silicone breakdown was noted. CONCLUSIONS Artificial muscle implanted in this short-term animal model was safe and functional in this preliminary study. We believe that EPAM devices will be a safe and viable option for restoration of facial motions in patients with irreversible facial paralysis. PMID:22986911
/sup 125/I-Labeled receptor ligands can be synthesized with specific activities exceeding 2000 Ci/mmol, making them nearly 70-fold more sensitive in receptor site assays than (mono) tritiated ligands. We have synthesized and characterized /sup 125/I-lysergic acid diethylamide (/sup 125/I-LSD), the first radioiodinated ligand for serotonin receptor studies. The introduction of /sup 125/I at the 2 position of LSD increased both the affinity and selectivity of this compound for serotonin 5-HT/sub 2/ receptors in rat cortex. The high specific activity of /sup 125/I-LSD and its high ratio of specific to nonspecific binding make this ligand especially useful for autoradiographic studies of serotonin receptor distribution. We have found that /sup 125/I-LSD binds with high affinity to a class of serotonin receptors in the CNS of the marine mollusk Aplysia californica.
/sup 125/I-LSD: a high sensitivity ligand for serotonin receptors
/sup 125/I-labeled receptor ligands offer unique advantages over their /sup 3/H-labeled counterparts. Carrier-free /sup 125/I-labeled ligands can be synthesized with specific activities of up to 2170 Ci/mmol while (mono) tritium labeled ligands are limited to 29 Ci/mmol. Therefore, /sup 125/I-labeled ligands can be approximately 70-fold more sensitive than /sup 3/H-labeled ligands in detecting receptor sites. In addition, /sup 125/I-labeled ligands emit relatively energetic X-rays and ..gamma..-rays which are readily detected by gamma counting equipment. The authors report here the serotonergic binding properties of /sup 125/I-LSD the first reported /sup 125/I-labeled ligand for serotonin receptors.
Study of a hydrophobic site on bovine alpha-lactalbumin by labeling with (125I)-TID
The hydrophobic, photoreactive probe 3-(trifluoromethyl)-3-(m-(/sup 125/I)iodophenyl) diazirine ((/sup 125/I)TID) labels apo-bovine alpha-lactalbumin but much less his Ca2+-form. The labeling of the apo-form is strong at protein concentrations of 0.5 mg ml-1 and increases with increasing concentration. Furthermore, increasing concentrations of NaCl, decrease the labeling of apo-alpha-lactalbumin with (/sup 125/I)TID.
Influence of glucose and urea on {sup 125}I transport across an anion exchange paper membrane
In order to study the influence of glucose and urea on the {sup 125}I transport across an anion exchange paper membrane, the transmembrane potential, the fluxes, and the concentrations of {sup 125}I, glucose and urea within the membrane were measured in the Na{sup 125}I concentration-cell system containing glucose or urea. Glucose and urea increased the membrane/solution distribution of the iodide ion, but scarcely affected the diffusion process of iodide ion within the membrane.
Binding and degradation of (/sup 125/I)human growth hormone in rat adipocytes
Iodinated human growth hormone (( /sup 125/I)hGH) binds to both specific and nonspecific sites on the surface of adipocytes isolated from the epididymal fat of normal rats. When adipocytes were incubated at 37 C with 1 nM (/sup 125/I)hGH, specific binding increased for 30-60 min and thereafter remained approximately constant as long as the hormone was present in the medium. About 90% of the /sup 125/I released was soluble in 5% trichloroacetic acid and was in the form of iodotyrosine. The rate of /sup 125/I release from specific binding sites decreased by a factor of 4 when the temperature was lowered from 37 to 17 C. Replacement of some of the sodium chloride in the buffer with 25 mM ammonium chloride had little or no effect on the amount on /sup 125/I that bound to cells when (/sup 125/I)hGH was present in the medium, but completely blocked the release of /sup 125/I from cells transferred to hormone-free medium. Ammonium chloride also significantly reduced both the release of /sup 125/I from nonspecific binding sites and the amount of /sup 125/I recovered in trichloroacetic acid-soluble form. Cloroquine, leupeptin, or colchicine nearly doubled the specific binding of (/sup 125/I)hGH after 180 min and markedly slowed the release of /sup 125/I when cells were transferred to hormone-free medium. All of these agents also significantly reduced the rate of release of /sup 125/I from nonspecific binding sites. Incubation of adipose tissue from hypophysectomized rats with ammonium chloride, leupeptin, or colchicine failed to alter the ability of GH to increase glucose oxidation, induce refractoriness, or promote lipolysis in the presence of theophylline.
The radioallergosorbent test is used for determining specific IgG-antibodies against mixed pollen allergens. Mixed pollen extract is coupled to bromcyan-activated paper discs as antigenic component and either /sup 125/I-anti-human-IgG or /sup 125/I-SpA is added after incubation with diluted serum to determine bound antibodies. The results show that, in the IgG-RAST, /sup 125/I-SpA is superior to the used /sup 125/I-anti-human-IgG for demonstration of bound antibodies. The concentration of the specific IgG-antibodies is determined using a reference calibration curve, which is derived from a series of dilutions of the reference serum.
The rates of internalization and degradation of /sup 125/-I-labeled desialylated cyanogen bromide fragment I of orosomucoid (AS-CNBr-I) and its reduced and carboxymethylated derivative (AS-RC-CNBr-I) were compared with those of /sup 125/I-labeled asialoorosomucoid (ASOR) in rat hepatocytes. At 30 nM the rates of internalization and degradation of /sup 125/I-AS-CNBr-I were greater than those of /sup 125/I-ASOR. /sup 125/I-AS-RC-CNBr-I also had a lower rate of internalization and degradation. In contrast to /sup 125/I-ASOR, when degradation was inhibited by 5 ..mu..M colchicine there was a significant intracellular accumulation of the smaller ligands. At 4/sup 0/C the hepatocytes were found to bind the fragmented ligands more than /sup 125/I-ASOR. Incubation of the cells with bound ligand at 37/sup 0/ indicated that diacytosis of /sup 125/I-ASOR was greater than the smaller ligands. Colchincine markedly enhanced diacytosis of /sup 125/I-ASOR. On the other hand, there were marked accumulation of the smaller ligands by colchicine. These results suggest that the rates of internalization, degradation and diacytosis of the ligand are affected by the size and conformation of the ligand through different rates of receptor binding and intracellular transport.
Preparation of 6-/sup 125/I-labeled amiloride derivatives
Amiloride and certain of its derivatives are effective inhibitors of Na/H antiporters and of epithelial Na channels. We describe a simple method for the preparation of a variety of pharmacologically active 6-iodoamiloride derivatives that are labeled with /sup 125/I at high specific radioactivity. 6-Dechloroamiloride derivatives (bearing a hydrogen atom instead of the chlorine at the 6 position of the amiloride molecule) are reacted with /sup 125/ICl, prepared by the oxidation of the iodide in Na/sup 125/I preparations. The /sup 125/I-labeled derivatives are separated from free /sup 125/I by anion exchange chromatography, or purified by thin layer chromatography. Both 6-dechloroamiloride and 5-(N-alkyl)-6-dechloroamiloride derivatives can be labeled by this method, with yields varying between 10 and 70%, depending on the ICl concentration and the structure of the 5-N-alkyl group. Efficient radiolabeling at high specific radioactivity also depends on the use of freshly prepared batches of /sup 125/I. Using carrier-free /sup 125/I, (/sup 125/I)6-iodoamiloride and (/sup 125/I)6-iodo-5-(N-tert-butyl)amiloride were prepared with yields of 27 and 22%, respectively. Potential applications of the /sup 125/I-labeled amiloride derivatives include ligand binding and affinity labeling experiments.
Transport of {sup 125}I and {sup 36}Cl across an anion-exchange paper membrane
The membrane characteristics controlling {sup 125}I and {sup 36}Cl transport across anion-exchange paper membranes are examined using three different paper membranes treated with different anion exchange groups: a trimethylhydroxypropylamino group, a diethylaminoethyl group, and a 50% quaternary diethylaminoethyl group. The membrane permeability for {sup 125}I is higher than that for {sup 36}Cl in all cases. Treatment with trimethylhydroxypropylamino group improves the {sup 125}I diffusion process, and the use of 50% quaternary diethylaminoethyl group improves the {sup 125}I solution/membrane distribution process.
Twiddler's Syndrome Complicating Neuromodulation Systems For Chronic Pain
Introduction: Voluntary or unvoluntary manipulation of a implanted pulse generator can lead to migration of the transducer wires and permanent malfunction of the device. This socalled Twiddler's syndrome has been described for pacemakers, implantable cardioverter-defibrillators and deep brain stimulators. Twiddler's syndrome can be expected at any subcutaneously implanted device accessible for patient manipulations. We report 2 cases, one treated with a spinal cord stimulator and the other with an implantable intrathecal infusion pump, presenting with Twiddler's syndrome. Material and Methods: Case 1 A 42-year-old man presented to the emergency department with diffuse pain, hot/cold flashes, nausea, jitteriness, and extreme tiredness. He was known to be treated with intrathecal morphine in...
Objectives This study sought to assess the impact of permanent pacemaker (PPM) implantation on clinical outcomes among patients undergoing transfemoral transcatheter aortic valve implantation (TAVI). Background TAVI is associated with atrioventricular-conduction abnormalities requiring PPM implantation in up to 40% among patients treated with self-expanding prostheses. Methods Between 2007 and 2010, 353 consecutive patients (mean age: 82.6 ± 6.1 years, log EuroSCORE: 25.0 ± 15.0%) with severe aortic stenosis underwent transfemoral TAVI at 2 institutions. Clinical outcomes were compared among 3 groups: (1) patients requiring PPM implantation after TAVI (PPM after TAVI), (2) patients without PPM before or after TAVI (no PPM), and (3) patients with PPM before TAVI (PPM before TA...
Antibacterial effects of silver-doped hydroxyapatite thin films sputter deposited on titanium
Since many orthopedic implants fail as a result of loosening, wear, and inflammation caused by repeated loading on the joints, coatings such as hydroxyapatite (HAp) on titanium with a unique topography have been shown to improve the interface between the implant and the natural tissue. Another serious problem with long-term or ideally permanent implants is infection. It is important to prevent initial bacterial colonization as existing colonies have the potential to become encased in an extracellular matrix polymer (biofilm) that is resistant to antibacterial agents. In this study, plasma-based ion implantation was used to examine the effects of pre-etching on plain titanium. Topographical changes to the titanium samples were examined and compared via scanning electron microscopy. Hydroxya...
Transcatheter aortic valve implantation (TAVI) is a novel treatment for high risk or inoperable patients with symptomatic severe aortic stenosis. However, significant atrioventricular (AV) conduction system abnormalities requiring permanent pacemaker (PPM) implantation might complicate this procedure. We used best subsets logistic regression analysis to identify the independent predictors for the development of high-degree AV block (HDAVB) among 70 patients who underwent TAVI at 3 referral centers in Israel from 2008 to 2010. The mean age of the study patients was 83 ± 4.6 years. Of the 70 patients, 28 (40%) developed AV conduction abnormalities requiring PPM implantation within 14 days (median 2) of the procedure. The indications for PPM implantation were HDAVB (n = 25), new-onset ...
Background Conduction disorders and permanent pacemaker (PPM) implantation are common complications in patients undergoing transcatheter aortic valve implantation (TAVI). Previous studies, evaluating small populations, have identified several different predictors of PPM implantation after TAVI. The aim of this study was to assess the incidence rate of conduction disorders and the predictors of postoperative PPM requirement in a large series of patients undergoing TAVI. Methods Data were analyzed from 181 consecutive patients at high-risk surgery who underwent TAVI at our institute between July 2007 and April 2011. All patients underwent implantation of the third-generation percutaneous self-expanding CoreValve® prosthesis (CoreValve, Inc., Irvine, CA, USA). In all patients, a 12-lead elec...
Background: Conduction abnormalities are frequent after transcatheter aortic valve implantation with the CoreValve (Medtronic, Minneapolis, MN) and are often treated with liberal permanent pacemaker (PPM) implantation. Our aim was to assess the 1-year outcome of a conservative approach to pacing and to identify its predictors. Methods: We analyzed 275 consecutive patients without a PPM before transcatheter aortic valve implantation who underwent successful CoreValve implantation at our 3 centers, sharing a conservative approach to pacing. Results: Of the 47 patients (17.1%) who developed postprocedural complete atrioventricular block, 14 recovered spontaneous atrioventricular conduction <72 hours and did not receive a PPM. Sixty-six patients (24.0%) received a PPM before discharge, and 74 ...
Introduction: High expression of the system L amino acid transporter has been observed in clinically important tissues including tumors and the blood-brain barrier. We examined amino acid transport system L selectivity of {sup 14}C(U)-L-tyrosine ({sup 14}C-Tyr), {sup 125}I-4-iodo-L-meta-tyrosine (4-{sup 125}I-mTyr), {sup 125}I-6-iodo-L-meta-tyrosine (6-{sup 125}I-mTyr), {sup 125}I-3-iodo-{alpha}-methyl-L-tyrosine ({sup 125}I-IMT) and {sup 125}I-3-iodo-L-tyrosine (3-{sup 125}I-Tyr) using Chinese hamster ovary cells (CHO-K1). Methods: Cells in the exponential growth phase were incubated with 18.5 kBq of labeled amino acid in 2 mL of phosphate-buffered saline-based uptake solution and an uptake solution with/without Na{sup +} at 37{sup o}C or 4{sup o}C. We examined the effects of the following compounds (1.0 mM) on transport: 2-(methylamino)isobutyric acid (a specific inhibitor of system A, in Na{sup +}-containing uptake solution); 2-amino-bicyclo[2,2,1]heptane-2-carboxylic acid (a specific inhibitor of system L, in Na{sup +}-free uptake solution); sodium azide and 2,4-dinitrophenol (NaN{sub 3} and DNP, inhibitors of the generation of adenosine triphosphate); p-aminohippurate and tetraethylammonium (PAH and TEA, inhibitors of organic anion and cation transporters); and L- and D-isomers of natural amino acids. Results: {sup 14}C-Tyr exhibited affinity for systems L, A and ASC. 4-{sup 125}I-mTyr and 3-{sup 125}I-Tyr exhibited high specificity for system L, whereas 6-{sup 125}I-mTyr and {sup 125}I-IMT exhibited affinity for both systems L and ASC. Uptake of 4-{sup 125}I-mTyr was markedly reduced by incubation at 4 {sup o}C, and was not significantly inhibited by NaN{sub 3}, DNP, PAH or TEA. The inhibition profiles of the L- and D-isomers of natural amino acids indicated that system L mediates the transport of 4-{sup 125}I-mTyr. Conclusions: 4-{sup 125}I-mTyr exhibited the greatest system L specificity (93.46{+-}0.13%) of all of the tested amino acids.
(Leu-B25)insulin is a low affinity insulin analog which does not increase the rate of dissociation of /sup 125/I-insulin from insulin receptors (i.e. does not display negative cooperativity). We have studied the characteristics of binding of this analog to IM-9 cultured lymphocytes, in order to determine the contribution of negative cooperativity to the curvilinear nature of Scatchard plots typical of insulin binding data. The affinity of (LeuB25)insulin for receptors was approximately 1% that of insulin, as determined by its ability to inhibit /sup 125/I-insulin binding. Monoiodinated preparations of insulin and of (LeuB25)insulin were produced, labeled in the tyrosine at position 14 of the A chain. These /sup 125/I-TyrA14-labeled species were used in all studies. Both native insulin and a serum containing antiinsulin receptor antibodies were equally potent at inhibiting binding of /sup 125/I-(LeuB25)insulin and /sup 125/I-native insulin, suggesting that they bind to the same population of receptors. Native insulin (100 ng/ml) increased the rate of dissociation of both /sup 125/I-insulin and /sup 125/I-(LeuB25)insulin. However, (LeuB25)insulin (2.5 micrograms/ml) did not increase the rates of dissociation of either /sup 125/I-insulin or /sup 125/I-(LeuB25)insulin (i.e. it did not display negative cooperativity). Competition curves and Scatchard plots were constructed using /sup 125/I-(LeuB25)insulin and unlabeled analog. Half-maximal inhibition of /sup 125/I-(LeuB25)insulin binding was seen at a (LeuB25)insulin concentration of approximately 500 ng/ml. More importantly, the Scatchard plot of these binding data was markedly curvilinear, as is typical of insulin binding data.
Tissue specificity of endothelin binding sites
A measurement was made of the binding of 125I-labeled endothelin (125I-ET) to crude membrane fractions prepared from rat aorta, atrium, ventricle, portal vein, trachea, lung parenchyma, vas deferens, ileum, bladder, and guinea-pig taenia coli and lung parenchyma. Scatchard analysis of 125I-ET binding in all tissues indicated binding to a single class of saturable sites. The affinity and density of 125I-ET binding sites varied between tissues. The Kd of 125I-ET binding was approximately 0.5 nM for rat aorta, trachea, lung parenchyma, ventricle, bladder, and vas deferens, and guinea-pig taenia coli and lung parenchyma, 1.8 nM for rat portal vein and atrium, and 3.3 nM for ileum. The Bmax of 125I-ET binding had the following rank order of density in rat tissues: trachea greater than lung parenchyma = vas deferens much greater than aorta = portal vein = atrium greater than bladder greater than ventricle = ileum. The properties of 125I-ET endothelin binding were characterized in rat ventricular membranes. 125I-ET binding was time dependent, reaching a maximum within 45-60 min at 25 degrees C. The calculated microassociation constant was 9.67 x 10(5) s-1 M-1. Only 15-20% of 125I-ET dissociated from its binding site even when dissociation was studied as long as 3 h. Preincubation of ventricular membranes with ET prevented binding of 125I-ET. 125I-ET binding was destroyed by boiling of ventricular membranes and was temperature, pH, and cation (Ca2+, Mg2+, and Na+) dependent.
Purpose: To demonstrate how postimplantation analysis is useful for improving permanent seed implantation and reducing toxicity. Patients and Methods: We evaluated 197 questionnaires completed by patients after permanent seed implantation (monotherapy between 1999 and 2003). For 70% of these patients, a computed tomography was available to perform postimplantation analysis. The index doses and volumes of the dose-volume histograms (DVHs) were determined and categorized with respect to the date of implantation. Differences in symptom scores relative to pretherapeutic status were analyzed with regard to follow-up times and DVH descriptors. Acute and subacute toxicities in a control group of 117 patients from an earlier study (June 1999 to September 2001) by Wust et al. (2004) were compared with a matched subgroup from this study equaling 110 patients treated between October 2001 and August 2003. Results: Improved performance, identifying a characteristic time dependency of DVH parameters (after implantation) and toxicity scores, was demonstrated. Although coverage (volume covered by 100% of the prescription dose of the prostate) increased slightly, high-dose regions decreased with the growing experience of the users. Improvement in the DVH and a reduction of toxicities were found in the patient group implanted in the later period. A decline in symptoms with follow-up time counteracts this gain of experience and must be considered. Urinary and sexual discomfort was enhanced by dose heterogeneities (e.g., dose covering 10% of the prostate volume, volume covered by 200% of prescription dose). In contrast, rectal toxicities correlated with exposed rectal volumes, especially the rectal volume covered by 100% of the prescription dose. Conclusion: The typical side effects occurring after permanent seed implantation can be reduced by improving the dose distributions. An improvement in dose distributions and a reduction of toxicities were identified with elapsed time between 1999 and 2003.
Purpose: Implantable devices routinely used for increasing spatial accuracy in modern image-guided radiation treatments (IGRT), such as fiducials or brachytherapy spacers, encompass the potential for in situ release of biologically active drugs, providing an opportunity to enhance the therapeutic ratio. We model this new approach for two types of treatment. Methods and Materials: Radiopaque fiducials used in IGRT, or prostate brachytherapy spacers ('eluters'), were assumed to be loaded with radiosensitizer for in situ drug slow release. An analytic function describing the concentration of radiosensitizer versus distance from eluters, depending on diffusion-elimination properties of the drug in tissue, was developed. Tumor coverage by the drug was modeled for tumors typical of lung stereotactic body radiation therapy treatments for various eluter dimensions and drug properties. Six prostate {sup 125}I brachytherapy cases were analyzed by assuming implantation of drug-loaded spacers. Radiosensitizer-induced subvolume boost was simulated from which biologically effective doses for typical radiosensitizers were calculated in one example. Results: Drug distributions from three-dimensional arrangements of drug eluters versus eluter size and drug properties were tabulated. Four radiosensitizer-loaded fiducials provide adequate radiosensitization for {approx}4-cm-diameter lung tumors, thus potentially boosting biologically equivalent doses in centrally located stereotactic body treated lesions. Similarly, multiple drug-loaded spacers provide prostate brachytherapy with flexible shaping of 'biologically equivalent doses' to fit requirements difficult to meet by using radiation alone, e.g., boosting a high-risk region juxtaposed to the urethra while respecting normal tissue tolerance of both the urethra and the rectum. Conclusions: Drug loading of implantable devices routinely used in IGRT provides new opportunities for therapy modulation via biological in situ dose painting.
MCPI: a sub-minute Monte Carlo dose calculation engine for prostate implants.
An accelerated Monte Carlo code [Monte Carlo dose calculation for prostate implant (MCPI)] is developed for dose calculation in prostate brachytherapy. MCPI physically simulates a set of radioactive seeds with arbitrary positions and orientations, merged in a three-dimensional (3D) heterogeneous phantom representing the prostate and surrounding tissue. MCPI uses a phase space data source-model to account for seed self-absorption and seed anisotropy. A "hybrid geometry" model (full 3D seed geometry merged in 3D mesh of voxels) is used for rigorous treatment of the interseed attenuation and tissue heterogeneity effects. MCPI is benchmarked against the MCNP5 code for idealized and real implants, for 103Pd and 125I seeds. MCPI calculates the dose distribution (2-mm voxel mesh) of a 103Pd implant (83 seeds) with 2% average statistical uncertainty in 59 s using a single Pentium 4 PC (2.4 GHz). MCPI is more than 10(3) and 10(4) times faster than MCNP5 for prostate dose calculations using 2- and 1-mm voxels, respectively. To illustrate its usefulness, MCPI is used to quantify the dosimetric effects of interseed attenuation, tissue composition, and tissue calcifications. Ignoring the interseed attenuation effect or slightly varying the prostate tissue composition may lead to 6% decreases of D100, the dose delivered to 100% of the prostate. The presence of calcifications, covering 1%-5% of the prostate volume, decreases D80, D90, and D100 by up to 32%, 37%, and 58%, respectively. In conclusion, sub-minute dose calculations, taking into account all dosimetric effects, are now possible for more accurate dose planning and dose assessment in prostate brachytherapy. PMID:16475768
Objectives This study evaluated the predictive factors and prognostic value of new-onset persistent left bundle branch block (LBBB) in patients undergoing transcatheter aortic valve implantation (TAVI) with a balloon-expandable valve. Background The predictors of persistent (vs. transient or absent) LBBB after TAVI with a balloon-expandable valve and its clinical consequences are unknown. Methods A total of 202 consecutive patients with no baseline ventricular conduction disturbances or previous permanent pacemaker implantation (PPI) who underwent TAVI with a balloon-expandable valve were included. Patients were on continuous electrocardiographic (ECG) monitoring during hospitalization and 12-lead ECG was performed daily until hospital discharge. No patient was lost at a median follow-up o...
Entrapment of Permanent Pacemaker Lead as the Cause of Tricuspid Regurgitation
Transthoracic 2-dimensional (D) echocardiography (echo) is often used to assess tricuspid regurgitation (TR) after implantation of permanent pacemakers. However, its ability to define the precise anatomical relationship between the tricuspid valve and the pacemaker lead is quite limited. This report presents a 58-year-old male with aggravation of TR after pacemaker implantation for heart block. Three-D echo precisely depicted the entrapment of the lead shaft in the fused and fibrotic septal and posterior tricuspid leaflets. The patient underwent tricuspid valve annuloplasty and the symptoms of right heart failure improved soon after the operation. (Circ J 2007; 71: 1169 - 1171)
An 87-year-old woman with complete atrioventricular block was admitted for permanent pacemaker implantation. The patient had a large thoracic aortic aneurysm that had been conservatively treated. Lead placement was not possible via the superior vena cava or the epicardial route because of the aneurysm. Therefore, we implanted a VVI pacemaker via the femoral approach. A unit was placed in a pouch on the right lower abdominal wall, and a lead was introduced into the right ventricle via the right femoral vein. The femoral vein approach is rarely used; however, it should be recognized as an effective alternative when the usual approach is difficult or impossible to be performed.
We present three cases of fixated vascular injection ports. Two patients had cystic fibrosis and one had an immunological defect. All catheters were made from polyurethane and implanted in adolescent patients. Indwelling time were 6-8 years. One patient's catheter was entirely integrated in the vessel wall and impossible to remove. In the other two cases, catheters were removed with great difficulty by the interventional radiologists. These cases raise important questions concerning the maximum indwelling time and the choice of catheter material when implanting permanent central venous catheters (CVCs) in adolescents. Furthermore, it highlights the importance of not breaking a CVC in the attempt to remove it.
Catheter Interventional Therapy in an Elderly Patient With Deep Vein Thrombosis and a Brain Tumor
A 92-year-old woman with a brain tumor developed swelling of the left lower extremity. Venography showed considerable thrombi from the left common iliac vein to the femoral vein. Following implantation of a temporary inferior vena cava filter, catheter aspiration therapy and catheter-directed thrombolysis were performed. Venography after 3 days showed disappearance of the thrombi and an improvement in vein flow. A permanent inferior vena cava filter was implanted. Local intensive thrombectomy and thrombolysis by catheter together with a temporary inferior vena cava filter were effective treatments in this elderly patient with deep vein thrombosis.
Successful Treatment of Primary Cardiac Lymphoma With Atrioventricular Nodal Block
A 69-year-old female suffering from third-degree atrioventricular block with syncope underwent permanent pacemaker implantation. However, she developed shortness of breath 2 months after the implantation. Blood tests revealed elevated levels of LDH, CRP, BNP, and SIL-2R. Transthoracic echocardiography showed thickened left and right atrial walls with mild pericardial effusion. A diagnosis was made based on a CT scan and histology. Although most primary cardiac malignant lymphomas are associated with a poor prognosis, the patient was treated successfully with chemotherapy.
Subacute Presentation of Right Ventricular Perforation after Pacemaker Implantation
We report an 87-year-old woman with right ventricular perforation due to a permanent pacemaker lead detected 4-days after implantation. The pacemaker lead was seen to perforate through the myocardium and pericardium and to reach the left pleural cavity. We removed the wire surgically by median sternotomy. The pericardial effusion was cloudy and yellowish, suggesting infection. However, no bacteria were detected by bacterial cultures of the pericardial effusion and pacing wire. The patient developed neither mediastinitis nor sepsis after the operation, and a new pacemaker was implanted safely one month later.
ObjectivesThe purpose of the present study was to present histological and immunohistochemical evidence showing the regenerative capacity of swine dental pulp stem cells (S-DPSCs) seeded on organic or synthetic scaffolds and implanted as hybrid root implants in the jaw bone of minipigs. MethodsImmature permanent incisor teeth and unerupted premolars at the early root-forming stage were extracted from three 7-month-old minipigs, and mesenchymal stem/progenitor cells were isolated from dental pulp. Cells were cryopreserved in liquid nitrogen. A year later, new permanent incisor and premolar teeth were extracted; pulp tissue was removed; and pieces of root canals of the extracted teeth, containing collagen or Poly(lactic-co-glycolic acid) scaffolds seeded with the autologous cryopreserved DPS...
Purpose Report the results of using a permanently implantable dosimeter in radiation therapy: determine specific adverse events, degree of migration, and acquire dose measurements during treatment to determine difference between expected and measured dose. Methods and Materials The Dose Verification System is a wireless, permanently implantable metal-oxide semiconductor field-effect transistor dosimeter using a bidirectional antenna for power and data transfer. The study cohort includes 36 breast (33 patients received two devices) and 29 prostate (21 patients received two devices) cancer patients. A total of 1,783 and 1,749 daily dose measurements were obtained on breast and prostate patients, respectively. The measurements were compared with the planned expected dose. Biweekly computed to...
Aim This study seeks to identify the optimal management strategy for patients with syncope in the context of bifascicular block and preserved left ventricular systolic function. Methods and results This multicentre, randomized, open label, parallel group pragmatic randomized trial will test the hypothesis that a strategy of empiric permanent pacemaker implantation in patients with syncope and bifascicular heart block improves future outcome more effectively than a strategy of therapy guided by prolonged monitoring with an implantable loop recorder (ILR). A total of 120 patients with bifascicular block, preserved left ventricular function, and ?1 syncopal spell in the preceding year will be randomized to receive a permanent pacemaker or ILR in at least 20 centres in Canada, the USA, ...
The aim of this prospective study was to evaluate the concept of intraoral welding as a suitable technique for fabricating a fixed restoration for the edentulous maxilla the day of surgery using standard and zygomatic implants. Ten consecutive patients (four men, six women; mean age, 62.3 ± 11.6 years) were involved in this study, each of whom had an edentulous atrophic maxilla and received two standard and two zygomatic implants. All implants were loaded immediately with a fixed prosthesis supported by an intraorally welded titanium framework. Definitive abutments were connected to the implants, and a titanium bar was welded to them using an intraoral welding unit. This framework was used to support the definitive prosthesis, which was fitted the day of implant placement. Patients were checked for swelling, pain, and framework stability at 1, 3, 6, and 12 months. A total of 20 immediately loaded standard and 20 zygomatic implants were used. The cases included in this study achieved a 100% prosthetic success rate at the 12-month follow-up. No fracture or radiographically detectable alteration of the welded frameworks was noticed. It is possible to successfully rehabilitate the edentulous atrophic maxilla with a permanently fixed prosthesis supported by an intraorally welded titanium framework attached to standard and zygomatic implants the day of surgery. PMID:22754908
Background and Objective: Unexpected venous occlusions or anatomic variants are encountered during de novo transvenous lead implantation. This study examined the prevalence and risk factors of venous abnormalities in patients undergoing de novo permanent pacemaker (PPM) implantation by the transvenous approach. Methods: The study involved 653 consecutive patients who underwent de novo PPM implantation. During the procedure, the venous network of the arms was evaluated using intravenous angiography. Results: Complete venous occlusion was observed in 5 of the 653 patients (0.77%). The lead was implanted on the right opposite site in 4 patients. There were a history of central catheter insertion in four patients, prior thoracic surgery in three, and chemotherapy in two. A persistent left superior vena cava (PLSVC) was observed in 4 patients (0.61%). PPM was implanted from the right opposite side in 2 patients. All PLSVC patients showed normal chest radiographs, but 3 of the 4 patients showed coronary sinus dilatation on echocardiography. Conclusions: Patients requiring transvenous pacing lead implantation rarely exhibit venous abnormalities. However, venous occlusion should be taken into consideration, particularly in patients with a history of insertion of central catheters, thoracic surgery, or chemotherapy. Careful echocardiography test for coronary sinus dilatation must be conducted to detect a PLSVC before the implantation.
Distribution, blood transport, and degradation of antidiuretic hormone in man.
The distribution, blood transport, and metabolic clearance of physiological concentrations of antidiuretic hormone were studied in 10 hydrated normal subjects with radioiodinated arginine vasopressin (125I-AVP). At 37 degrees C no binding of 125I-AVP to plasma proteins could be demonstrated, but som...
Internalization of ricin in Chinese hamster ovary cells.
Internalization of ricin into Chinese hamster ovary cells has been investigated. Combined treatment with galactose and pronase at 0 degrees C resulted in a complete release of surface-bound [125I]ricin into the media. Galactose-pronase-resistant cell-bound [125I]ricin represents internalized ricin m...
The membrane-reactive, photoactivatable probe 125I-TID [3-(trifluoromethyl)-3-(m-[125I]iodophenyl)-3H-diazirine] was found to label the M protein of vesicular stomatitis virus about 40% as much as G protein in intact virions, in agreement with labeling studies with other probes. By analyzing limited...
Recycling of epidermal growth factor in a human pancreatic carcinoma cell line.
PANC-1 human pancreatic carcinoma cells readily bound and internalized 125I-labeled epidermal growth factor (EGF). Bound 125I-labeled EGF was then partially processed to a number of high molecular weight acidic species. Percoll gradient centrifugation of cell homogenates indicated that the majority ...
Binding of 125I-insulin to the isolated glomeruli of rat kidney.
To investigate a possible action of insulin on the glomerulus, the binding 125I-insulin to the isolated glomeruli prepared from rat kidney was examined. When incubated at 22 degrees C, 125I-insulin binding proceeded with time and reached a steady state at 45 min at which time nonspecific binding was...
Interactions of Standard Antibody with Australia Antigens in Au Ag-Ab Radioimmunoassay
Human antisera against Australia (Au) antigen have been characterized by liquid-phase radioimmunoassay (RIA) for their precipitation of 125I-labeled Au antigen. The end-point dilutions of sera (anti-Au) which precipitated 50% of 125I-Au antigen by RIA correlated well with complement fixation titers ...
Radiolabeled human Factor VIII was used to study its survival in normals and patients with classic hemophilia, and to study the heterogeneity of Factor VIII; Purified Factor VIII was radiolabeled with 125iodine (125I-VIII) without loss of its structural integrity. The survival of 125I-VIII was studi...
Tryptic soy broth (TSB)-grown cells of Staphylococcus aureus isolated from acute and chronic bovine mastitis bound mainly 125I-fibronectin (Fn) [corrected], whereas strains of nine species of coagulase-negative staphylococci showed a predominant interaction with 125I-collagen (Cn) [corrected] type I...
The gastrin receptor antagonist, CR2093, competed with 125I-gastrin-17 (5 x 10(-10) M) for binding to gastrin receptors on the rat pancreatic adenocarcinoma, AR42J (CR2093 concentration inducing 50% of 125I-gastrin-17 binding (IC50) was 8 x 10(-5) M), on the human gastric adenocarcinoma, MKN45 (IC50...
Radioimmunofluorescent antibody technique for detection of reovirus antigen in cell culture.
Antibody against reovirus type I must partially purified and conjugated with fluorescein isothiocyanate (FITC). The FITC-labeled antibody was then conjugated with 125I. A gamma globulin fraction of normal sera was similarly labeled with FITC followed by a 131I label. The FITC + 125I-labeled immune r...
An angiogenin-binding protein from endothelial cells.
A 42-kDa bovine protein that binds bovine angiogenin [angiogenin binding protein (AngBP)] has been identified as a dissociable cell-surface component of calf pulmonary artery endothelial cells and a transformed bovine endothelial cell line, GM7373. Binding of 125I-labeled bovine angiogenin (125I-Ang...
How neurons convert the presence of factors at their axon terminals into signals that affect mechanisms in their cell bodies is unknown, but retrograde axonal transport of the factors themselves may be involved. Nerve growth factor (NGF) and leukemia inhibitory factor (LIF) have previously been shown to produce changes in cell bodies of sympathetic neurons when applied to their peripheral neurites, and it is well established that NGF is retrogradely transported along sympathetic axons. In this study we show that 125I-LIF applied to terminal neurites of rat sympathetic neurons in compartmented cultures is retrogradely transported, but at a much lower level compared to the retrograde transport of 125I-NGF. Transport of 125I-LIF was competed by cotreatment with unlabeled LIF and was blocked by cotreatment with dinitrophenol. The rate of 125I-LIF transport was independent of NGF concentration. However, both 125I-LIF and 125I-NGF transport was reduced by pretreating neurons with LIF. SDS-PAGE analysis showed that retrogradely transported radiolabel which accumulated in cell body-containing extracts following transport of both 125I-LIF and 125I-NGF consisted of intact as well as partially processed species. Radiolabel also accumulated in the medium bathing the cell bodies and migrated near the dye front on SDS-PAGE, implying that both factors were extensively degraded and released by the neurons. These results are consistent with the suggestion that the retrograde transport of LIF, as thought for NGF, may be important for retrograde signaling mechanisms. PMID:7512056
The interactions of /sup 125/I-multiplication stimulating activity (MSA) and /sup 125/I-ovine somatomedin with receptors on skeletal muscle satellite cells are described. Specific binding of /sup 125/I-MSA/rIGF-II was inhibited by MSA/rIGF-II and oSm but not by insulin. Binding of /sup 125/I-oSm was inhibited by MSA/rIGF-II, oSm and insulin. In addition, 24-h pre-incubation of satellite cells with insulin increased the amount of /sup 125/I-MSA/rIGF-II bound, but insulin concentrations below 550 ..mu..g/l had no effect on the subsequent binding of /sup 125/I-oSm. Preincubation of cultures with oSm or MSA/rIGF-II decreased the subsequent binding of /sup 125/I-oSm and /sup 125/I-MSA/rIGF-II. These preliminary experiments suggest that oSm is similar to IGF-I in its binding characteristics and that primary cultures of skeletal muscle satellite cells possess type I and type II IGF receptors.
A rapid, simple, and sensitive 125I-postlabeling technique has been developed to allow detection of DNA-protein cross-links induced by environmental contaminants and carcinogens. This method is based on specific incorporation of 125I into tyrosine residues associated with DNA. Cultured Chinese hamst...
Immunoreactivity of /sup 125/I-papain labelled by different methods
Three different methods of papain iodination (with chloramine-T, lactoperoxidase and conjugation with Bolton-Hunter reagent) have been compared. The highest yield of /sup 125/I-papain could be obtained using lactoperoxidase which enabled to achieve the highest immunoreactivity. /sup 125/I-papain, labelled this way, is suitable for the radioimmunoassay of papain.
Radiation-induced neoplasms of the brain
The histopathology of two patients with radiation-induced neoplasms of the brain following therapeutic irradiation for intracranial malignancies is described. The second neoplasms were an atypical meningioma and a polymorphous cell sarcoma, respectively. They occurred 12 and 23 years after irradiation (4000 rad), within the original field of irradiation. In both cases, the radiation-induced tumors were histologically distinct from the initial medulloblastomas. Both patients were retreated with local irradiation using permanent implantation of radioactive iodine-125 seeds.
Familial Sick Sinus Syndrome With Atrioventricular Conduction Disturbance
A family with sick sinus syndrome is presented: a mother and her 2 daughters affected with sinus node dysfunction. Electrophysiological studies revealed abnormal atrioventricular conduction in the 2 daughters. All 3 individuals were implanted with a permanent pacemaker to relieve their symptoms. Endomyocardial biopsy from the right ventricle of one daughter showed disarrangement, degeneration, myocyte necrosis and interstitial fibrosis suggestive of myocardial disease. (Jpn Circ J 1998; 62: 788 - 790)
Complete Atrioventricular Block Secondary to Lithium Therapy
Sinus node dysfunction has been reported most frequently among the adverse cardiovascular effects of lithium. In the present case, complete atrioventricular (AV) block with syncopal attacks developed secondary to lithium therapy, necessitating permanent pacemaker implantation. Serum lithium levels remained under or within the therapeutic range during the syncopal attacks. Lithium should be used with extreme caution, especially in patients with mild disturbance of AV conduction. (Circ J 2008; 72: 847 - 849)
Purpose: To determine the possible effects of (125)I-to-DNA distance on the magnitude and mechanism of Auger-electron induced-double-strand break (DSB) production. Materials and methods: We have synthesized a series of (125)I-labeled Hoechst (H) derivatives ((125)IE-H, (125)IB-H, (125)I-C(8)-H and (125)I-C(12)-H). While all four molecules share a common DNA minor groove binding bis-benzimidazole motif, they are designed to position (125)I at varying distances from the DNA helix. Each Hoechst derivative was incubated at 4°C in phosphate buffered saline (PBS) together with supercoiled (SC) (3)H-pUC19 plasmid DNA (ratio 3:1) ± the •OH scavenger dimethyl sulfoxide (DMSO) (0.2 M). Aliquots were analyzed on agarose gels over time and DSB yields per decay of (125)I atom were determined. Docking of the iodinated compounds on a DNA molecule was carried out to determine the distance between the iodine atom and the central axis of DNA. Results: In the absence of DMSO, the results show that the DSB yields decrease monotonically as the (125)I atom is distanced - by 10.5 Å to 13.9 Å - from the DNA helix ((125)IEH: 0.52 ± 0.01; (125)IB-H: 0.24 ± 0.03; (125)I-C(8)-H: 0.18 ± 0.02; (125)I-C(12)-H: 0.10 ± 0.00). In the presence of DMSO, DSB yields for (125)IEH (0.49 ± 0.02) and (125)IB-H (0.26 ± 0.04) remain largely unchanged indicating that DSB are entirely produced by direct effects. Strikingly, (125)I-C(8)-H or (125)I-C(12)-H, did not produce detectable DSB in the presence of DMSO under similar conditions suggesting when (125)I atom is positioned >?12 Å from the DNA, DSB are entirely produced by indirect effects. Conclusion: These results suggest that at a critical distance between the (125)I atom and the DNA helix, DSB production switches from an 'all' direct to an 'all' indirect mechanism, the latter situation being comparable to the decay of (125)I free in solution. These experimental findings were correlated with theoretical expectations based on microdosimetry. PMID:22732063
N-(1-Naphthyl)-N'-(3-[{sup 125}I]-iodophenyl)-N'-methylguanidine ([{sup 125}I]-CNS 1261) was synthesized as a potential radioligand to image N-methyl-D-aspartate (NMDA) receptor activation. [{sup 125}I]-CNS 1261 was prepared by radioiodination of N-(1-naphthyl)-N'-(3-tributylstannylphenyl)-N'-methylguanidine using Na{sup 125}I and peracetic acid. [{sup 125}I]-CNS 1261 uptake in vivo reflected NMDA receptor distribution in normal rat brain, whereas in ischemic rat brain, uptake was markedly increased in areas of NMDA receptor activation. Radiolabeled CNS 1261 appears to be a good candidate for further development as a single photon emission computed tomography tracer in the investigation of NMDA receptor activation in cerebral ischemia.
In vivo autoradiographic benzodiazepine receptor imaging with [sup 125]I-Iomazenil (Ro 16-0154)
The biodistribution of [sup 125]I-Iomazenil (Ro 16-0154), a benzodiazepine receptor antagonist, was examined using in vivo autoradiography of gerbil brain. [sup 125]I-Iomazenil was administrated i.v. into male gerbils, and autoradiography was prepared from coronary sections of the animals decapitated at 5, 60, 120 and 180 min after injection. Initial uptake images (5 min) of [sup 125]I-Iomazenil were thought to show blood flow distribution. On the images obtained 120-180 min after administration, high activity of [sup 125]I-Iomazenil was observed in the cerebral cortex, amygdala, hippocampus, globus pallidus, thalamus, hypothalamus, superior colliculus, substantia nigra and cerebellar cortex in the areas of which benzodiazepine receptor concentration was reported to be high. However, low activity was observed in the caudate-putamen. Accumulation of [sup 125]I-Iomazenil was blocked by pre-administration of flumazenil. [sup 123]I-Ro 16-0154 has a high potentiality for benzodiazepine receptor mapping by SPECT. (author).
N-iodoacetyltyramine: Preparation and use in sup 125 I labeling by alkylation of sulfhydryl groups
Preparation and use of N-iodoacetyltyramine in generation of {sup 125}I-labeled compounds is described. The kinetics of alkylation of N-acetylcysteine by N-iodoacetyltyramine (k2 = 3.0 M-1 s-1) and N-chloroacetyltyramine (k2 = 0.12 M-1 s-1) indicate that N-iodoacetyltyramine is more useful for labeling sulfhydryl-containing compounds to high specific activity with {sup 125}I. Conditions for preparation of carrier-free {sup 125}I-labeled N-iodoacetyl-3-monoiodotyramine in 50% yield based on starting iodide are described. The high degree of group specificity of N-iodoacetyl-3-monoiodotyramine reaction with sulfhydryl groups is demonstrated by the high reactivity toward sulfhydryl-containing bovine serum albumin and low reactivity toward N-ethylmaleimide-blocked bovine serum albumin and IgG. {sup 125}I-labeled N-iodoacetyl-3-monoiodotyramine was also used to prepare an {sup 125}I-labeled ACTH derivative that retains full biological activity, further demonstrating the selectivity toward reactions with sulfhydryl groups.
An autoradiographic survey of mouse brain nicotinic acetylcholine receptors defined by null mutants
Nine nicotinic receptor subunits are expressed in the central nervous system indicating that a variety of nicotinic acetylcholine receptors (nAChR) may be assembled. A useful method with which to identify putative nAChR is radioligand binding. In the current study the binding of [^1^2^5I]a-bungarotoxin, [^1^2^5I]a-conotoxinMII, 5[^1^2^5I]-3-((2S)-azetidinylmethoxy)pyridine (A-85380), and [^1^2^5I]epibatidine has been measured autoradiographically to provide data on many nAChR binding sites. Each binding site was evaluated semi-quantitatively for samples prepared from wild-type and a2, a4, a6, a7, b2, b4, a5 and b3 null mutant mice. Deletion of the a7 subunit completely and selectively eliminated [^1^2^5I]a-bungarotoxin binding. The binding of [^1^2^5I]a-conotoxinMII was eliminated in most ...
Six children with neuroblastoma and one with ganglioneuroma received (/sup 125/I) metaiodobenzylguanidine (MIBG) before major surgery. Uptake of (/sup 125/I)MIBG in the excised tissues was measured by scintillation counting, and the material was submitted for histopathology. The ranges of uptake of (/sup 125/I)MIBG, expressed as percent of the injected dose per gram of tissue, were as follows: for neuroblastoma 0.0013-0.071, for ganglioneuroma 0.0017-0.0028, and for non-neoplastic control tissues 0.0002-0.011. The quantitative uptake of (/sup 125/I)MIBG by neuroblastoma varied between different patients and between different parts of individual tumors. The more undifferentiated tumors took up more (/sup 125/I)MIBG and may be more likely to respond to targeted radiotherapy with MIBG.
Japanese quail were doubly-labeled with 125I (carrier free, as sodium iodide) and 144Ce (.015 micromol/100 g, as trichloride). by 1 hr after administration, the growing oocytes and the ova had accumulated 29% of the 125I and 21% of the 144Ce. By 18 hr, the accumulations were 30% of the 125I and 79% of the 144Ce. Lanthanum (15 micromol/100 g, as trichloride), given iv 5 min before the radionuclides, resulted in 1-hr accumulations of 4% for 125I and 23% for 144Ce. On fractionation of the oocyte yolk, 86% of the 125I present in the yolk was found in the low density fraction and 69% of the 144Ce remained with the phosvitin fraction. These results were consistent with the suggestion of Schjeide and Prahlad (1977) that, in plasma, iodide becomes associated with the calcium-containing vitellogenin complex.
Aims: High rates of permanent pacemaker (PPM) implantation are reported after transcatheter aortic valve implantation (TAVI) using the Medtronic CoreValve® system. The Accutrak™ catheter is designed to allow a?more predictable landing zone. Little is known about the real clinical impact of this catheter. The aims of this paper were to describe the potential impact of the Accutrak™ catheter on the accuracy of positioning a 26 or 29 mm CoreValve® across the aortic annulus and its impact on the need for a?pacemaker. Methods and results: A?total of 134 patients were treated with the CoreValve® Accutrak™ system at two French centres (Lille and Toulouse). Mean age was 82.4±4.7 years; logistic EuroSCORE was 24.3±9.5%. Procedural success rate was 99.2%; mean depth of implantation was 4.9?mm. A?final position between 0 and 6?mm was achieved in 85.8% of the patients. All-cause mortality at 30 days was 6%. The PPM implantation rate was 10.6%. Due to a?limited number of events, we could not identify any predictor of need for a PPM: pre-existing right bundle branch block (RBBB) (OR 2.72 [0.63-11.87], p=ns), use of a 29 mm prosthesis (OR 2.73 [0.33-22.90], p=ns) and left ventricular septal hypertrophy (OR 2.63 [0.08-83.32], p=ns). Conclusions: In this cohort of patients treated with the CoreValve® Accutrak™ system, the incidence of permanent pacemaker implantation was low, which may be a?consequence of an average small implantation depth. The Accutrak™ catheter seems to be helpful in achieving higher and more predictable implants. Operators could standardise their technique to place the CoreValve® prostheses less than 6 mm below the aortic annulus. PMID:22706377
Aims: High rates of permanent pacemaker (PPM) implantation are reported after transcatheter aortic valve implantation (TAVI) using the Medtronic CoreValve® system. The Accutrak™ catheter is designed to allow a more predictable landing zone. Little is known about the real clinical impact of this catheter. The aims of this paper were to describe the potential impact of the Accutrak™ catheter on the accuracy of positioning a 26 or 29 mm CoreValve® across the aortic annulus and its impact on the need for a pacemaker. Methods and results: A total of 134 patients were treated with the CoreValve® Accutrak™ system at two French centres (Lille and Toulouse). Mean age was 82.4±4.7 years; logistic EuroSCORE was 24.3±9.5%. Procedural success rate was 99.2%; mean depth of implantation was 4.9 mm. A final position between 0 and 6 mm was achieved in 85.8% of the patients. All-cause mortality at 30 days was 6%. The PPM implantation rate was 10.6%. Due to a limited number of events, we could not identify any predictor of need for a PPM: pre-existing right bundle branch block (RBBB) (OR 2.72 [0.63-11.87], p=ns), use of a 29 mm prosthesis (OR 2.73 [0.33-22.90], p=ns) and left ventricular septal hypertrophy (OR 2.63 [0.08-83.32], p=ns). Conclusions: In this cohort of patients treated with the CoreValve® Accutrak™ system, the incidence of permanent pacemaker implantation was low, which may be a consequence of an average small implantation depth. The Accutrak™ catheter seems to be helpful in achieving higher and more predictable implants. Operators could standardise their technique to place the CoreValve® prostheses less than 6 mm below the aortic annulus. PMID:22995081
Case report: autotransplantation for a missing permanent maxillary incisor.
Patients with nonrestorable or missing anterior teeth are typically seen by their general or pediatric dentist who directs the course of consultation, referral, and treatment. In the mixed dentition stage, loss of permanent maxillary incisors is usually treated by various forms of removable/fixed prosthetic appliances. Because premolars are developing during this time period, transplantation of an available premolar to an incisor position is a viable alternative, that may provide a better biological substitute for a missing incisor than other choices. The purpose of this case report was to describe the treatment of the loss of a permanent maxillary central incisor by transplantation of a maxillary first premolar to the incisor position. Autotransplantation allowed normal alveolar bone development and a future option of permanent restoration without implants or partial dentures. Autotransplantation should be given consideration as a reasonable option for the treatment of missing incisors in mixed dentition. PMID:18481582
Fate of circulating renin in conscious rats
Highly purified /sup 125/I-labeled rat renal renin (/sup 125/I-renin) was given intravenously to conscious rats to study the fate of circulating renin. Specific antirat renin antiserum was used to identify the labeled renin molecules. In sham-operated rats, the disappearance of /sup 125/I-renin from the plasma showed two exponential components with a half-life of 6.7 +/- 0.4 min for the rapid component and 65.1 +/- 5.7 min for the slow component. The metabolic clearance rate was 11.4 +/- 1.0 ml X min-1 X kg-1. In bilaterally nephrectomized rats, the metabolic clearance rate of /sup 125/I-renin was reduced by 55%, but the half-life of the slow component remained unchanged. Seventy percent hepatectomy caused a 54% decrement in the metabolic clearance and prolonged the half-life of the slow component. Five minutes after injection of /sup 125/I-renin, approximately 59 and 11% of the administered /sup 125/I-renin had accumulated in the liver and the kidneys, respectively, and at later time points the /sup 125/I-renin was highly concentrated in these organs. High-performance liquid chromatographic analysis of the liver and kidney extracts demonstrated that /sup 125/I-renin was catabolized by these organs. Biliary excretion of /sup 125/I-renin was negligible. Urinary excretion of /sup 125/I-renin up to 120 min was approximately 2% of the injected dose. We conclude that both the liver and the kidney are responsible for the clearance of circulating renin, with participation of the liver being predominant.
The catabolism of streptokinase (SK) and polyethylene glycol derivatives of SK (PEG-SK) were studied in mice. The clearance and catabolism of SK:plasmin (SK:Pm) and PEG-SK:Pm activator complexes were also investigated. Native 125I-SK cleared rapidly (t1/2 = 15 minutes) from the circulation, with the majority of the ligand accumulating in the liver and gastrointestinal (GI) tract and a substantial fraction also localizing in the kidneys. SK, which was removed from the plasma by the liver, was secreted into bile and then the GI tract. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that 125I-SK recovered from liver and bile was homogeneous and of the same molecular weight (mol wt approximately 50,200) as native SK. PEG-125I-SK cleared slowly (t1/2 greater than 200 minutes), with more than 80% of the preparation localizing in liver and GI tract. The PEG-125I-SK secreted into the bile was also intact. The bile containing 125I-SK was incubated with stoichiometric amounts of plasminogen and electrophoresed under nondenaturing conditions. This study demonstrated that the secreted SK was able to form SK:Pg complexes. SDS-PAGE also showed activation of 125I-Pg that was incubated with recovered bile containing the SK. 125I-SK:Pm catabolism was also studied. In these experiments, the mol wt approximately 42,000 fragment obtained when SK is cleaved by plasmin was found in the bile. This fragment of 125I-SK was not recovered as part of a complex with plasmin, consistent with our previous observations that catabolism of SK:Pm involves transfer of the plasmin to plasma proteinase inhibitors while SK is catabolized independently. By contrast, when PEG-125I-SK:Pm was injected into mice, only intact PEG-125I-SK was found in the bile, consistent with our previous observations that the PEG derivatization blocks its degradation by plasmin.
In vivo binding of /sup 125/I-LSD to serotonin 5-HT/sub 2/ receptors in mouse brain
The binding of /sup 125/I-LSD (2-(/sup 125/I)-lysergic acid diethylamide) was studied in various mouse brain regions following intravenous injection of the radioligand. The high specific activity of /sup 125/I-LSD enabled the injection of low mass doses (14ng/kg), which are well below the threshold for induction of any known physiological effect of the probe. The highest levels of /sup 125/I-LSD binding were found in the frontal cortex, olfactory tubercles, extra-frontal cortex and striatum while the lowest level was found in the cerebellum. Binding was saturable in the frontal cortex but increased linearly in the cerebellum with increasing doses of /sup 125/I-LSD. Serotonergic compounds potently inhibited /sup 125/I-LSD binding in cortical regions, olfactory tubercles, and hypothalamus but had no effect in the cerebellum. Dopaminergic compounds caused partial inhibition of binding in the striatum while adrenergic compounds were inactive. From these studies the authors conclude that /sup 125/I-LSD labels serotonin 5-HT/sub 2/ receptor sites in cortical regions with no indication that other receptor sites are labeled. In the olfactory tubercles and hypothalamus, /sup 125/I-LSD labeling occurs predominantly or entirely at serotonic 5-HT/sub 2/ sites. In the striatum, /sup 125/I-LSD labels approximately equal proportions of serotonergic and dopaminergic sites. These data indicate that /sup 125/I-LSD labels serotonin receptors in vivo and suggests that appropriate derivatives of 2I-LSD may prove useful for tomographic imaging of serotonin 5-HT/sub 2/ receptors in the mammalian cortex.
Radioiodinated VEGF to image tumor angiogenesis in a LS180 tumor xenograft model
Introduction: Angiogenesis is essential for tumor growth or metastasis. A method involving noninvasive detection of angiogenic activity in vivo would provide diagnostic information regarding antiangiogenic therapy targeting vascular endothelial cells as well as important insight into the role of vascular endothelial growth factor (VEGF) and its receptor (flt-1 and KDR) system in tumor biology. We evaluated radioiodinated VEGF{sub 121}, which displays high binding affinity for KDR, and VEGF{sub 165}, which possesses high binding affinity for flt-1 and low affinity for KDR, as angiogenesis imaging agents using the LS180 tumor xenograft model. Methods: VEGF{sub 121} and VEGF{sub 165} were labeled with {sup 125}I by the chloramine-T method. Biodistribution was observed in an LS180 human colon cancer xenograft model. Additionally, autoradiographic imaging and immunohistochemical staining of tumors were performed with {sup 125}I-VEGF{sub 121}. Results: {sup 125}I-VEGF{sub 121} and {sup 125}I-VEGF{sub 165} exhibited strong, continuous uptake by tumors and the uterus, an organ characterized by angiogenesis. {sup 125}I-VEGF{sub 121} uptake in tumors was twofold higher than that of {sup 125}I-VEGF{sub 165} (9.12{+-}98 and 4.79{+-}1.08 %ID/g at 2 h, respectively). {sup 125}I-VEGF{sub 121} displayed higher tumor to nontumor (T/N) ratios in most normal organs in comparison with {sup 125}I-VEGF{sub 165}. {sup 125}I-VEGF{sub 121} accumulation in tumors decreased with increasing tumor volume. Autoradiographic and immunohistochemical analyses confirmed that the difference in {sup 125}I-VEGF{sub 121} tumor accumulation correlated with degree of tumor vascularity. Conclusion: Radioiodinated VEGF{sub 121} is a promising tracer for noninvasive delineation of angiogenesis in vivo.
An autoradiographic survey of mouse brain nicotinic acetylcholine receptors defined by null mutants.
Nine nicotinic receptor subunits are expressed in the central nervous system indicating that a variety of nicotinic acetylcholine receptors (nAChR) may be assembled. A useful method with which to identify putative nAChR is radioligand binding. In the current study the binding of [(125)I]?-bungarotoxin, [(125)I]?-conotoxinMII, 5[(125)I]-3-((2S)-azetidinylmethoxy)pyridine (A-85380), and [(125)I]epibatidine has been measured autoradiographically to provide data on many nAChR binding sites. Each binding site was evaluated semi-quantitatively for samples prepared from wild-type and ?2, ?4, ?6, ?7, ?2, ?4, ?5 and ?3 null mutant mice. Deletion of the ?7 subunit completely and selectively eliminated [(125)I]?-bungarotoxin binding. The binding of [(125)I]?-conotoxinMII was eliminated in most brain regions by deletion of either the ?6 or ?2 subunit and is reduced by deletion of either the ?4 or ?3 subunit. The binding of 5[(125)I]A-85380 was completely eliminated by deletion of the ?2 subunit and significantly reduced by deletion of the ?4 subunit. Most, but not all, ?4-independent sites require expression of the ?6 subunit. The effect of gene deletion on total [(125)I]epibatidine binding was very similar to that on [(125)I]A-85380 binding. [(125)I]Epibatidine also labels ?4* nAChR, which was readily apparent for incubations conducted in the presence of 100nM cytisine. The effects of ?3 gene deletion could not be evaluated, but persistence of residual sites implies the expression of ?3* nAChR. Taken together these results confirm and extend previously published evaluations of the effect of nAChR gene deletion and help to define the nAChR subtypes measurable by ligand binding. PMID:21575611
We have synthesized 16 alpha-iodo-4,9-estradien-17 beta-ol-3-one (delta 9-16 alpha-iodo-19-nortestosterone (delta 9-INT)) labeled with 125I (delta 9-(16 alpha-125I)INT) to provide a new gamma-emitting photoaffinity ligand for the progesterone receptor that has many advantages over the currently available (3H)R5020. We have characterized the interaction of delta 9-(16 alpha-125I)INT with the rabbit uterine progesterone receptor and have demonstrated the usefulness of this compound for studies of receptor structure. The binding of 2 nM (3H)progesterone to receptor in rabbit uterine cytosol was specifically competed for by 19-nortestosterone, 16 alpha-iodo-19-nortestosterone, and delta 9-INT. Scatchard analysis demonstrated that delta 9-(16 alpha-125I)INT and (3H)progesterone estimated the same number of binding sites in rabbit uterine cytosol, with a Kd for delta 9-(16 alpha-125I)INT of about 2.7 nM. The binding of delta 9-(16 alpha-125I)INT was inhibited by both progesterone and R5020, whereas testosterone, estradiol, and 5 alpha-dihydrotestosterone were ineffective. In cytosol, delta 9-(16 alpha-125I)INT covalently labeled the same mol wt receptor forms as (3H)R5020. Although the efficiency of cross-linking was similar for (3H)R5020 (3%) and delta 9-(16 alpha-125I)INT (4%), the radioactivity was 10-fold greater due to the higher specific activity of delta 9-(16 alpha-125I)INT and the lack of sample quench. The use of delta 9-(16 alpha-125I)INT greatly increases the sensitivity and efficiency of the photoaffinity labeling technique; it will provide a valuable tool for further studies of the progesterone receptor, allowing the detection of receptor in dilute cytosol after gel electrophoresis under denaturing conditions.
The characteristics of alpha-1 adrenergic receptors in rat cerebral cortex were examined using the radioiodinated alpha-1 adrenergic receptor antagonist ((/sup 125/I)BE). (/sup 125/I)BE labeled a single class of high-affinity binding sites in a particulate fraction of rat cerebral cortex with mass action kinetics and a KD of 57 pM. The binding of (/sup 125/I)BE was inhibited by various alpha adrenergic receptor antagonists, partial agonists and full agonists. The potency of these compounds in competing for the (/sup 125/I)BE binding sites suggested that (/sup 125/I)BE was labeling alpha-1 adrenergic receptors in rat cerebral cortex. In the absence of a physiological concentration of NaCl in the assay medium there was a small (20%) decrease in the density of (/sup 125/I)BE binding sites with no effect on the KD value. The absence of NaCl also caused a 4-fold increase in the potency of norepinephrine in competing for (/sup 125/I)BE binding sites. All drugs competed for (/sup 125/I) BE binding sites with Hill coefficients greater than 0.86, except for oxymetazoline which had a Hill coefficient of 0.77. Scatchard analysis of specific (/sup 125/I)BE binding in the presence of various competing drugs showed that the inhibition by both agonists and antagonists was purely competitive, but the inhibition by oxymetazoline was complex. Treatment of the particulate fraction of rat cerebral cortex with 0.2 to 200 nM phenoxybenzamine for 10 min caused a dose-dependent decrease in the density of (/sup 125/I) BE binding sites which could be mostly blocked by the presence of norepinephrine during the phenoxybenzamine exposure.
Neuropeptide Y (NPY) and peptide YY (PYY) receptors in rat brain
1. Specific binding sites for neuropeptide Y (NPY) and peptide YY (PYY) were investigated in rat brain areas using quantitative receptor autoradiography with {sup 125}I-Bolton-Hunter NPY ({sup 125}I-BH-NPY) and {sup 125}I-PYY, radioligands for PP-fold family peptides receptors. 2. There were no differences between localization of {sup 125}I-BH-NPY and {sup 125}I-PYY binding sites in the rat brain. High densities of the binding sites were present in the anterior olfactory nucleus, lateral septal nucleus, stratum radiatum of the hippocampus, posteromedial cortical amygdaloid nucleus, and area postrema. 3. In cold ligand-saturation experiments done in the presence of increasing concentrations of unlabeled NPY and PYY, {sup 125}I-BH-NPY and {sup 125}I-PYY binding to the stratum radiatum of the hippocampus, layer I of the somatosensory frontoparietal cortex, molecular layer of the cerebellum, and area postrema was single and of a high affinity. There was a significant difference between the affinities of {sup 125}I-BH-NPY (Kd = 0.96 nM) and {sup 125}I-PYY binding (Kd = 0.05 nM) to the molecular layer of the cerebellum. The binding of the two radioligands to the other areas examined had the same affinities. 4. When comparing the potency of unlabeled rat pancreatic polypeptide (rPP), a family peptide of NPY and PYY, to inhibit the binding to the areas examined, rPP displaced {sup 125}I-BH-NPY and {sup 125}I-PYY binding to the area postrema more potently than it did the binding to the stratum radiatum of the hippocampus, layer I of the somatosensory frontoparietal cortex, and molecular layer of the cerebellum. 5. Thus, the quantitative receptor autoradiographic method with {sup 125}I-BH-NPY and {sup 125}I-PYY revealed differences in binding characteristics of specific NPY and PYY binding sites in different areas of the rat brain. The results provide further evidence for the existence of multiple NPY-PYY receptors in the central nervous system.
Biopsy and implantation of the seminal vesicles
PurposeTo describe the technique and outcomes of seminal vesicle biopsy (SVB) and permanent implantation in patients with T3b prostate cancer. Methods and MaterialsIntermediate- and high-risk prostate cancer patients who elected brachytherapy as their treatment of choice were offered SVB for either Gleason score ?7, prostate-specific antigen levels >10ng/mL, or clinical stage ?T2b. Three cores were taken from both seminal vesicles at the base of the prostate using transrectal ultrasound. Patients with a positive SVB and either a negative pelvic lymph node dissection or pelvic computerized tomogram were treated with a combination of a partial implant followed by 45Gy of external beam irradiation therapy. During the seed implant, sources were positioned in the anterior wall of the semi...
Abstract in portuguese Descrevemos um caso raro de implante de marcapasso definitivo em gestante, portadora de valvopatia mitral reumática, previamente submetida à valvoplastia percutânea por cateter-balão. A paciente apresentava bloqueio atrioventricular de grau avançado, de causa não-reversível, sintomático e manifesto no 3º trimestre da gestação. Abstract in spanish Describimos un caso raro de implante de marcapaso definitivo en gestante, portadora de valvulopatía mitral reumática, previamente sometida a valvuloplastia percutánea por catéter balón La paciente presentaba bloqueo atrioventricular en grado avanzado, de causa irreversible, sintomático y manifiesto en el 3º trimestre de gestación. Abstract in english We describe a rare case of permanent pacemaker implantation in a pregnant woman with rheumatic mitral valve disease previously undergoing percutaneous balloon valvuloplasty. She presented symptomatic advanced atrioventricular block of non-reversible cause and manifest in the third trimester of gestation.
Surface characterization of anodized zirconium for biomedical applications
Mechanical properties and corrosion resistance of zirconium make this material suitable for biomedical implants. Its good in vivo performance is mainly due to the presence of a protective oxide layer that minimizes corrosion rate, diminishes the amount of metallic ions released to the biological media and facilitates the osseointegration process. Since the implant surface is the region in contact with living tissues, the characteristics of the surface film are of great interest. Surface modification is a route to enhance both biocompatibility and corrosion resistance of permanent implant materials. Anodizing is presented as an interesting process to modify metal surfaces with good reproducibility and independence of the geometry. In this work the surface of zirconium before and after anodi...
The brachytherapy of prostate by permanent implants is included in the armamentarium of localized prostate cancers with external radiotherapy and radical prostatectomy. The quality evaluation of implantation is essential for the patient and the team managing him. Our retrospective work consisted in analysing the whole of dosimetry data and urinary, digestive and sexual functional results of patients treated in our centers. conclusion: the post-implantation dosimetry analysis is essential to improve the technique and to understand the evolutions. The method of scanning evaluation is difficult but is currently the most used by its accessibility. The low urinary, rectal and sexual morbidity of the brachytherapy makes of this treatment an attractive technique for the patients should be well selected. (N.C.)
Reconstruction after substantial osseous, cutaneous, and muscular tissue loss following a mandibular resection is a challenge. The use of a fibular free flap is an outstanding, but delicate, treatment option. These grafts, using the double-barrel technique, can achieve an almost complete reconstruction of the mandibular defect. The challenge posed by these treatments is to achieve an end result that is both functional and esthetically pleasing-an endeavor that requires a defined prosthetic plan prior to complete microsurgical reconstruction. Using a detailed clinical case, this article discusses the importance of planning the mandible reconstruction with double-barrel fibular graft in view of an implant-supported fixed partial denture. Immediate implant loading was even possible in this case. This approach allows improvement of the final esthetic and functional result of such a complex rehabilitation. Maxillofacial reconstructive surgery should seek to establish a near-as-normal anatomic situation that will allow a permanent implant rehabilitation that is both esthetic and durable. PMID:20712447
Complex Retrieval of Embedded IVC Filters: Alternative Techniques and Histologic Tissue Analysis
Purpose We evaluated the safety and effectiveness of alternative endovascular methods to retrieve embedded optional and permanent filters in order to manage or reduce risk of long-term complications from implantation. Histologic tissue analysis was performed to elucidate the pathologic effects of chronic filter implantation. Methods We studied the safety and effectiveness of alternative endovascular methods for removing embedded inferior vena cava (IVC) filters in 10 consecutive patients over 12 months. Indications for retrieval were symptomatic chronic IVC occlusion, caval and aortic perforation, and/or acute PE (pulmonary embolism) from filter-related thrombus. Retrieval was also performed to reduce risk of complications from long-term filter implantation and to eliminate the need for li...
Ti-6Al-4V-0.5B-A Modified Alloy for Implants Produced by Metal Injection Molding
Abstract Permanent implants have to fulfill a great variety of requirements related to both material and geometry. In addition, manufacturing costs play a role, which is getting steadily more and more important. Metal Injection Molding (MIM) of titanium alloy powders may contribute to the development of implants with higher functionality without increasing the price. High degree of freedom with regard to geometry, high material efficiency, and the possibility to create even porous structures are main benefits from applying this technique. Today, even long-term implants made from Ti-6Al-4V by MIM are commercially available. However, in order to improve fatigue behavior it is beneficial to perform a minor variation of Ti-6Al-4V by adding a low amount of boron. In this paper the mechanical, b...
Objectives: -To define the incidence of stent thrombosis (ST) and/or AMI (ST/AMI) associated with temporary or permanent suspension of dual antiplatelet therapy (DAPT) after coronary drug-eluting stent (DES) implantation in -real-world- patients, and additional factors influencing these events. Background: -Adherence to DAPT is critical for avoiding ST following DES implantation. However, the outcomes of patients undergoing antiplatelet therapy withdrawal following DES implantation remain to be clearly described. Methods: -Patients receiving DES from 05/01/2003 to 05/01/2008 were identified from a single-center registry. Complete follow-up data were available for 5,681 patients (67% male, age 66--11 years, duration 1,108-446 days) who were included in this analysis. Results: -Uninterrupted...
BACKGROUND: The objective of this study was to determine whether the addition of low-dose-rate brachytherapy or androgen-deprivation therapy (ADT) improves clinical outcome in patients with high-risk prostate cancer (HiRPCa) who received dose-escalated radiotherapy (RT). METHODS: Between 1995 and 2010, 958 patients with HiRPCa were treated at Schiffler Cancer Center (n = 484) or at the University of Michigan (n = 474) by receiving either dose-escalated external-beam RT (EBRT) (n = 510; minimum prescription dose, 75 grays [Gy]; median dose, 78 Gy) or combined-modality RT (CMRT) consisting of (103) Pd implants (n = 369) or (125) I implants (n = 79) both with pelvic irradiation (median prescription dose, 45 Gy). The cumulative incidences of biochemical failure (BF) and prostate cancer-specific mortality (PCSM) were estimated by using the Kaplan-Meier method and Fine and Gray regression analysis. RESULTS: The median follow-up was 63.2 months (interquartile range, 35.4-99.0 months), and 250 patients were followed for >8 years. Compared with CMRT, patients who received EBRT had higher prostate-specific antigen levels, higher tumor classification, lower Gleason sum, and more frequent receipt of ADT for a longer duration. The 8-year incidence BF and PCSM among patients who received EBRT was 40% (standard error, 38%-44%) and 13% (standard error, 11%-15%) compared with 14% (standard error, 12%-16%; P received CMRT. On multivariate analysis, the hazard ratios (HRs) for BF and PCSM were 0.35 (95% confidence interval [CI], 0.23-0.52; P received CMRT. CONCLUSIONS: In this retrospective comparison, both low-dose-rate brachytherapy boost and ADT were associated with decreased risks of BF and PCSM compared with EBRT. Cancer 2012. © 2012 American Cancer Society. PMID:22893254
Abstract in spanish Introducción: La braquiterapia prostática con semillas de I125 está indicada en pacientes con cáncer de próstata organoconfinado. Nuestro objetivo es describir la población tratada en nuestra institución mediante implante permanente con semillas de I125, las características dosimétricas de la técnica y los resultados preliminares de nuestra serie en cuanto a evolución y toxicidad. Material y métodos: Entre mayo 2000 y marzo de 2003 fueron tratados 130 paciente (more) s con implante permanente transperineal de semillas de I125. Previamente a todos se les realizó volumetría mediante una ecografía prostática transrectal para determinar la configuración del implante, número de semillas y su localización en la próstata con el fin de obtener una adecuada cobertura del PTV (planed target volume o volumen planificado para tratar). Distribución por estadios: 75,72% T1c; 24,28% T2a. Gleason Abstract in english Introduction: The prostate brachitherapy with I125 seeds has an indication in patients with organconfined prostate cancer. Our objective is to describe the population trated in our institution with permanent I125 seeds implants, the dosimetric characteristics of the technique and the preliminary results of our group-study in terms of evolution and toxicity. Material and methods: Between May 2000 and March 2003, a 130 patients with permanent implants of I125 seeds were tra (more) ted. Beforehand we did prostate volumetric with transrectum prostate ecography in order to asses the configuration of the implant, number of seeds and their place in the prostate with the objective to get a fine coverage of PTV (planet target volume). Stage distribution: 75.72% T1c; 24.28% T2a. Gleason
Purpose: The aim of this study was to use permanent seed implants in the breast and describe our experience with 15 cases, using iodine seed implants as a tumor bed boost. Methods and Materials: Breasts were fixed with a thermoplastic sheet, a template bridge applied, the thorax scanned and the images rotated to be perpendicular to the implant axis. Skin, heart, and lung were delineated. A preplan was made, prescribing 50 Gy to the clinical target volume (CTV), consisting in this boost series of nearly a quadrant. Iodine (125) seeds were stereotactically implanted through the template, and results were checked with a postplan computed tomographic (CT) scan. Results: The breast was immobilized reproducibly. Simulation, scanning, and implant were performed without difficulties. Preplan CTV D90% (the dose delivered to 90% of the CTV) was 66 Gy, and postoperative fluoroscopic or CT scan checks were satisfactory. Pre- and postplan dose-volume histogram showed good organ sparing: mean postplan skin, heart, and lung V30 Gy (the organ volume receiving a dose of 30 Gy) of 2 {+-} 2.2 mL, 0.24 {+-} 0.34 mL, and 3.5 {+-} 5 mL, respectively. No short-term toxicity above Grade 1 was noted, except for transient Grade 3 neuropathy in 1 patient. Conclusions: Seeds remained in the right place, as assessed by fluoroscopy, absence of significant pre- to postplan dose-volume histogram change for critical organs, and total irradiated breast volume. The method could be proposed as a boost when high dosimetric selectivity is required (young patients after cardiotoxic chemotherapy for left-sided cancer). This boost series was a preliminary step before testing partial breast irradiation by permanent seed implant in a prospective trial.
Hemostatic changes in normal pregnancy
Background and Objectives The growing implantations of electrophysiological devices in the context of increasing rates of chronic antithrombotic therapy in cardiovascular disease patients underscore the importance of an effective periprocedural prophylactic strategy for prevention of bleeding complications. We assessed the risk of significant bleeding complications in patients receiving anti-platelet agents or anticoagulants at the time of permanent pacemaker (PPM) implantation. Subjects and Methods We reviewed bleeding complications in patients undergoing PPM implantation. The use of aspirin or clopidogrel was defined as having taking drugs within 5 days of the procedure and warfarin was changed to heparin before the procedure. A significant bleeding complication was defined as a bleeding incident requiring pocket exploration or blood transfusion. Results Permanent pacemaker implantations were performed in 164 men and 96 women. The mean patient age was 73±11 years old. Among the 260 patients, 14 patients took warfarin (in all of them, warfarin was changed to heparin at least 3 days before procedure), 54 patients took aspirin, 4 patients took clopidogrel, and 25 patients took both. Significant bleeding complications occurred in 8 patients (3.1%), all of them were patients with heparin bridging (p<0.0001). Heparin bridging markedly increased the length of required hospital stay when compare with other groups and the 4 patients (1.5%) that underwent the pocket revision for treatment of hematoma. Conclusion This study suggests that hematoma formation after PPM implantation was rare, even among those who had taken the anti-platelet agents. The significant bleeding complications frequently occurred in patients with heparin bridging therapy. Therefore, heparin bridging therapy was deemed as high risk for significant bleeding complication in PPM implantation. PMID:15764641
Endocytosis of heat-denatured albumin by cultured rat Kupffer cells
Purified Kupffer cells were obtained by centrifugal elutriation of sinusoidal cells isolated by pronase treatment of the rat liver. The endocytosis of radioactively labeled heat-aggregated colloidal albumin (CA /sup 125/I) was investigated in maintenance cultures of the purified Kupffer cells. The endocytic capacity of the cells was studied during 4 days of culture. Maximum uptake was observed after 24 hr of culture, with a gradual decline during the following days. When the uptake was measured after incubation with increasing concentrations of CA /sup 125/I, a saturation effect was observed. This finding and the observed high rate of uptake are strong indications that receptor sites on the cell membrane are involved in the mechanism of endocytosis. The uptake of CA /sup 125/I by Kupffer cells was inhibited by the metabolic inhibitors fluoride and antimycin A, indicating that endocytosis of CA /sup 125/I is dependent on energy derived from both glycolysis and mitochondrial respiration. The mechanism of internalization may also require the action of microfilaments as well as intact microtubules, since both cytochalasin B and colchicine inhibited the uptake of CA /sup 125/I. The intracellular degradation of CA /sup 125/I by Kupffer cells was strongly inhibited by chloroquine but not by colchicine. The degradation of ingested CA /sup 125/I occurred within the Kupffer cell lysosomes.
Hepatic microsomes isolated from untreated male rats or from rats pretreated with phenobarbital (PB) or 3-methylcholanthrene (3-MC) were labeled with the hydrophobic, photoactivated reagent 3-(trifluoromethyl)-3-(m-(/sup 125/I)iodophenyl)diazirine ((/sup 125/I)TID). (/sup 125/I)TID incorporation into 3-MC- and PB-induced liver microsomal protein was enhanced 5- and 8-fold, respectively, relative to the incorporation of (/sup 125/I)TID into uninduced liver microsomes. The major hepatic microsomal cytochrome P-450 forms inducible by PB and 3-MC, respectively designated P-450s PB-4 and BNF-B, were shown to be the principal polypeptides labeled by (/sup 125/I)TID in the correspondingly induced microsomes. Trypsin cleavage of (/sup 125/I)TID-labeled microsomal P-450 PB-4 yielded several radiolabeled fragments, with a single labeled peptide of Mr approximately 4000 resistant to extensive proteolytic digestion. The following experiments suggested that TID binds to the substrate-binding site of P-450 PB-4. (/sup 125/I)TID incorporation into microsomal P-450 PB-4 was inhibited in a dose-dependent manner by the P-450 PB-4 substrate benzphetamine. In the absence of photoactivation, TID inhibited competitively about 80% of the cytochrome P-450-dependent 7-ethoxycoumarin O-deethylation catalyzed by PB-induced microsomes with a Ki of 10 microM; TID was a markedly less effective inhibitor of the corresponding activity catalyzed by microsomes isolated from uninduced or beta-naphthoflavone-induced livers.
The effects of bile salts on the radioimmunoassay of hormonal peptides
The effect of bile salts on RIAs of secretin, glucagon, insulin, and gastrin have been studied. Increasing concentrations of the sodium salts of taurocholic, glycochenodeoxycholic, taurochenodeoxycholic, glycocholic, and taurodeoxycholic acids progressively inhibit the binding of 125I-secretin to specific antibody, resulting in significant lowering of the B/F ratio at concentrations as low as 0.04 mM and almost complete inhibition at concentrations above 2.4 mM. The nonspecific inhibition by taurodeoxycholate results in a B/F vs. concentration curve resembling a secretion standard curve. The binding of 125I-secretin to charcoal is also inhibited by increasing concentrations of bile salts, although this effect is less marked than their effects on the immune reaction. The binding of 125I-glucagon, 125I-insulin, and 125I-gastrin to specific antisera is also inhibited by sodium taurocholate. Insulin binding is least affected. However, gastrin binding is inhibited by sodium taurocholate at a concentration as low as 0.2. The binding of 125I-insulin and 125I-gastrin to charcoal is also inhibited by sodium taurocholate. Thus bile salts interfere in the RIA of hormonal peptides by inhibiting both the immune reaction and the binding of labeled antigen to charcoal. These nonspecific effects must therefore be considered in RIA of body fluids containing high concentrations of bile salts. Treatment of plasma samples with anionic-binding resins can eliminate interference caused by high bile salt concentrations. However, these resins will also remove anionic hormonal peptides such as gastrin.
Povidone-iodine solution is widely used to disinfect the skin surface or prevent suppuration during human and animal surgery. Using radioisotope 125I, we examined whether iodine may be absorbed and then concentrated in the thyroid gland when povidone-iodine solution is applied to the skin of rats or mice. The competition for 125I uptake was examined in mice and rats after the application of povidone iodine to the skin. We also traced the process of absorbed 125I in the thyroid gland during the fixation for tissue preparations. Povidone-iodine applied to the skin significantly reduced the uptake of 125I both in mice and rats. Significant flux of 125I from the thyroid gland in povidone-iodine treated animals was noted during the thyroid fixation of tissue preparations. From these results, povidone-iodine application to the skin instead of stable KI administration may be practical for preventing the uptake of 125I by the thyroid gland during 125I compound administration for medical therapy. In animal experiments concerning thyroid functions, careful attention must be paid when povidone-iodine is used for disinfection in animal surgery.
In vivo characterization of insulin uptake by dog renal cortical epithelium
In vivo 125I-labeled insulin uptake by dog renal tubular epithelium was studied using the single-pass multiple indicator dilution (MID) method and analyzed by a computer-assisted model of transcapillary exchange and substrate-cell interaction. Anesthetized dogs received an intrarenal arterial bolus of multiple tracers: (3H)dextran greater than 70 kDa (plasma reference), (14C)inulin (extracellular reference), and 125I-insulin. Rapid serial sampling of the renal venous and urine outflows was performed. The renal venous outflow curves of 125I-insulin fell below (14C)inulin implying postglomerular extraction and antiluminal membrane (ALM) uptake. The fractional urine recovery of 125I-insulin was less than 0.03, indicating luminal tubular uptake of filtered hormone. After intravenous infusion of unlabeled insulin, repeat MID runs with tracer revealed saturable ALM uptake as evidenced by the 125I-insulin renal venous outflow curves approaching (14C)inulin. Luminal tubular uptake was unchanged and therefore unsaturable. The 125I-insulin renal venous data were studied using three mathematical models, incorporating postglomerular reversible binding, irreversible binding or transport. The best fit was obtained using the transport model. The modeling analysis is consistent with either uptake into a virtual epithelial membrane space (i.e., insulin never enters the cell but binds to or is distributed along the ALM) or insulin actually enters the intracellular compartment. In vivo uptake of 125I-insulin ALM is characterized by a Km of 15.44 nM.
Neuropeptide Y (NPY) receptor binding sites have been localized in the rat brain by in vitro autoradiography using picomolar concentrations of both 125I-NPY and 125I-peptide YY (PYY) and new evidence provided for differentially localized receptor subtypes. Equilibrium binding studies using membranes indicate that rat brain contains a small population of high-affinity binding sites and a large population of moderate-affinity binding sites. 125I-PYY (10 pM) is selective for high-affinity binding sites (KD = 23 pM), whereas 10 pM 125I-NPY labels both high- and moderate-affinity sites (KD = 54 pM and 920 pM). The peptide specificity and affinity of these ligands in autoradiographic experiments match those seen in homogenates. Binding sites for 125I-PYY are most concentrated in the lateral septum, stratum oriens, and radiatum of the hippocampus, amygdala, piriform cortex, entorhinal cortex, several thalamic nuclei, including the reuniens and lateral posterior nuclei, and substantia nigra, pars compacta, and pars lateralis. In the brain stem, 125I-PYY sites are densest in a variety of nuclei on the floor of the fourth ventricle, including the pontine central grey, the supragenual nucleus, and the area postrema. 125I-NPY binding sites are found in similar areas, but relative levels of NPY binding and PYY binding differ regionally, suggesting differences in sites labeled by the two ligands. These receptor localizations resemble the distribution of endogenous NPY in some areas, but others, such as the hypothalamus, contain NPY immunoreactivity but few binding sites.
Mechanism of tubular uptake on human growth hormone in perfused rat kidneys
The mechanism of tubular uptake of labeled human growth hormone ((125I)hGH), a low molecular weight protein (approximate 21,5000 daltons), was studied in isolated perfused rat kidneys. Fractional reabsorption (FR) of (125I)hGH was decreased from 94 to 77% over a period of 80 min as perfusate oncotic pressure was lowered by reducing the albumin concentration from 7.5 to 2.5 g/100ml, whereas greater reductions in fractional sodium (delta 35%) and fluid reabsorption (delta 42%) occurred, indicating that tubular (125I)hGH uptake is likely a specific process not directly dependent upon net fluid and sodium reabsorption. Absolute absorption rates of (125I)hGH filtered loads were inhibited by cytochalasin B, a microfilament disrupter when kidneys were perfused with either albumin concentration. Cytochalasin B inhibited (125I)hGH absorption in both a dose-and time-related manner. The low dose of cytochalasin B (2.5 micrograms/ml) decreased (125I)hGH absorption without significantly altering sodium, fluid or glucose reabsorption. With high doses (5 and 10 micrograms/ml), cytochalasin B affected tubular absorption of (125I)hGH to an extent much greater than sodium, fluid and glucose reabsorption. Inhibition of cytochalasin B on FR(125I)hGH was poorly correlated with the concurrent inhibition of FRNa and FRH2O. Accordingly, tubular reabsorption of (125I)hGH is not directly linked to that of sodium, fluid and glucose. The present studies are consistent with the hypothesis that renal absorption of low molecular-weight proteins is via an endocytotic process involving microfilaments.
Thyroid glands from turtles (Chrysemys dorbigni) pretreated with potassium iodide were incubated with /sup 125/I-insulin in the presence or absence of unlabeled insulin, in order to study its specific uptake. At 24 degrees, the specific uptake reached a plateau at 180 min of incubation. The dose of bovine insulin that inhibited 50% of the /sup 125/I-insulin uptake was 2 micrograms/ml of incubation medium. Most of the radioactive material (71%) extracted from the gland, after 30 min incubation with /sup 125/I-insulin, eluted in the same position as labeled insulin on Sephadex G-50. Only 24% eluted in the salt position. After 240 min incubation, increased amount of radioactivity appeared in the Na/sup 125/I position. When bovine insulin was added together with the labeled hormone, a substantial reduction of radioactivity was observed in the insulin and Na/sup 125/I elution positions. Dissociation studies were performed at 6 degrees in glands preincubated with /sup 125/I-insulin either at 24 or 6 degrees. The percentage of trichloroacetic acid (TCA)-soluble radioactive material in the dissociation medium increased with incubation time at both temperatures. However, the degradation activity was lower at 6 than at 24 degrees. The addition of bovine insulin to the incubation buffer containing /sup 125/I-insulin reduced the radioactive degradation products in the dissociated medium. Chloroquine or bacitracin inhibited the degradation activity. Incubation of thyroid glands with /sup 125/I-hGH or /sup 125/I-BSA showed values of uptake, dissociation, and degradation similar to those experiments in which an excess of bovine insulin was added together with the labeled hormone. Thus, by multiple criteria, such as specific uptake, dissociation, and degradation, the presence of insulin-binding sites in the turtle thyroid gland may be suggested.
The retrograde axonal transport of intravenously (i.v.) administered /sup 125/I-nerve growth factor (/sup 125/I-NGF) was examined in mesenteric nerves innervating the small bowel of rats with streptozocin (STZ) diabetes using methods described in detail in the companion article. The accumulation of /sup 125/I-NGF distal to a ligature on the ileal mesenteric nerves of diabetic animals was 30-40% less than in control animals. The inhibition of accumulation of /sup 125/I-NGF in diabetic animals was greater at a ligature tied 2 h after i.v. administration than at a ligature tied after 14 h, which suggests that the diabetic animals may have a lag in initiation of NGF transport in the terminal axon or retardation of transport at some site along the axon. The /sup 125/I-NGF transport defect was observed as early as 3 days after the induction of diabetes, a time before the development of structural axonal lesions, and did not worsen at later times when dystrophic axonopathy is present. Both the ileal mesenteric nerves, which eventually develop dystrophic axonopathy in experimental diabetes, and the jejunal mesenteric nerves, which never develop comparable structural alterations, showed similar /sup 125/I-NGF transport deficits, suggesting that the existence of the transport abnormality does not predict the eventual development of dystrophic axonal lesions. Autoradiographic localization of /sup 125/I-NGF in the ileal mesenteric nerves of animals that had been diabetic for 11-13 mo demonstrated decreased amounts of /sup 125/I-NGF in transit in unligated paravascular nerve fascicles. There was, however, no evidence for focal retardation of transported /sup 125/I-NGF at the sites of dystrophic axonal lesions.
Interleukin-1 receptors in mouse brain: Characterization and neuronal localization
The cytokine interleukin-1 (IL-1) has a variety of effects in brain, including induction of fever, alteration of slow wave sleep, and alteration of neuroendocrine activity. To examine the potential sites of action of IL-1 in brain, we used iodine-125-labeled recombinant human interleukin-1 (( 125I)IL-1) to identify and characterize IL-1 receptors in crude membrane preparations of mouse (C57BL/6) hippocampus and to study the distribution of IL-1-binding sites in brain using autoradiography. In preliminary homogenate binding and autoradiographic studies, (125I)IL-1 alpha showed significantly higher specific binding than (125I)IL-1 beta. Thus, (125I)IL-1 alpha was used in all subsequent assays. The binding of (125I)IL-1 alpha was linear over a broad range of membrane protein concentrations, saturable, reversible, and of high affinity, with an equilibrium dissociation constant value of 114 +/- 35 pM and a maximum number of binding sites of 2.5 +/- 0.4 fmol/mg protein. In competition studies, recombinant human IL-1 alpha, recombinant human IL-1 beta, and a weak IL-1 beta analog. IL-1 beta +, inhibited (125I)IL-1 alpha binding to mouse hippocampus in parallel with their relative bioactivities in the T-cell comitogenesis assay, with inhibitory binding affinity constants of 55 +/- 18, 76 +/- 20, and 2940 +/- 742 pM, respectively; rat/human CRF and human tumor necrosis factor showed no effect on (125I)IL-1 alpha binding. Autoradiographic localization studies revealed very low densities of (125I)IL-1 alpha-binding sites throughout the brain, with highest densities present in the molecular and granular layers of the dentate gyrus of the hippocampus and in the choroid plexus. Quinolinic acid lesion studies demonstrated that the (125I)IL-1 alpha-binding sites in the hippocampus were localized to intrinsic neurons.
Introduction: Multiple myeloma (MM) is a plasma cell malignancy characterized by accumulation of malignant, terminally differentiated B cells in the bone marrow. Despite advances in therapy, MM remains an incurable disease. Novel therapeutic approaches are, therefore, urgently needed. Auger electron-emitting radiopharmaceuticals are attractive for targeted nano-irradiation therapy, given that DNA of malignant cells is selectively addressed. Here we evaluated the antimyeloma potential of the Auger electron-emitting thymidine analogue {sup 125}I-labeled 5-iodo-4'-thio-2'-deoxyuridine ([{sup 125}I]ITdU). Methods: Cellular uptake and DNA incorporation of [{sup 125}I]ITdU were determined in fluorodeoxyuridine-pretreated KMS12BM, U266, dexamethasone-sensitive MM1.S and -resistant MM1.R cell lines. The effect of stimulation with interleukin 6 (IL6) or insulin-like growth factor 1 (IGF1) on the intracellular incorporation of [{sup 125}I]ITdU was investigated in cytokine-sensitive MM1.S and MM1.R cell lines. Apoptotic cells were identified using Annexin V. Cleavage of caspase 3 and PARP was visualized by Western blot. DNA fragmentation was investigated using laddering assay. Therapeutic efficiency of [{sup 125}I]ITdU was proven by clonogenic assay. Results: [{sup 125}I]ITdU was shown to be efficiently incorporated into DNA of malignant cells, providing a promising mechanism for delivering highly toxic Auger radiation emitters into tumor DNA. [{sup 125}I]ITdU had a potent antimyeloma effect in cell lines representing distinct disease stages and, importantly, in cell lines sensitive or resistant to the conventional therapeutic agent, but was not toxic for normal plasma and bone marrow stromal cells. Furthermore, [{sup 125}I]ITdU abrogated the protective actions of IL6 and IGF1 on MM cells. [{sup 125}I]ITdU induced massive damage in the DNA of malignant plasma cells, which resulted in efficient inhibition of clonogenic growth. Conclusion: These studies may provide a novel treatment strategy for overcoming resistance to conventional therapy in multiple myeloma.
Iodinated recombinant human nerve growth factor (125I-rhNGF) stimulated neurite formation in PC12 cell cultures with a half-maximal potency of 35-49 pg/ml, compared with 39-52 pg/ml for rhNGF. In quantitative ligand autoradiography, the in vitro equilibrium binding of 125I-rhNGF to brain sections showed a 10-fold regional variation in density and was saturable, reversible, and specifically displaced by up to 74% with rhNGF or murine NGF (muNGF). At equilibrium, 125I-rhNGF bound to these sites with high affinity and low capacity (Bmax less than or equal to 13.2 fmol/mg of protein). Calculation of 125I-rhNGF binding affinity by kinetic methods gave average Kd values of 24 and 31 pM. Computer-generated maps revealed binding in brain regions not identified previously with 125I-muNGF, including hippocampus; dentate gyrus; amygdala; paraventricular thalamus; frontal, parietal, occipital, and cingulate cortices; nucleus accumbens; olfactory tubercle; subiculum; pineal gland; and medial geniculate nucleus. NGF binding sites were distributed in a 2-fold increasing medial-lateral gradient in the caudate-putamen and a 2-fold lateral-medial gradient in the nucleus accumbens. 125I-rhNGF binding sites were also found in most areas labeled by 125I-muNGF, including the interpedunucular nucleus, cerebellum, forebrain cholinergic nuclei, caudoventral caudate-putamen, and trigeminal nerve nucleus. 125I-rhNGF binding sites were absent from areas replete with low-affinity NGF binding sites, including circumventricular organs, myelinated fiber bundles, and choroid plexus. The present analysis provides an anatomical differentiation of high-affinity 125I-rhNGF binding sites and greatly expands the number of brain structures that may respond to endogenous NGF or exogenously administered rhNGF.
Characterization and applications of monoclonal antibodies to the prolactin receptor
Monoclonal antibodies (mAbs) were produced in BALB/c mice immunized with partially purified PRL receptors from rat liver. Two mAbs (T1 and T6) were able to completely inhibit (125I)ovine PRL ((125I)oPRL) binding to solubilized rat liver PRL receptors, while two other mAbs (U5 and U6) showed only a small effect on PRL binding, but were able to precipitate hormone-receptor complexes. Scatchard analysis of (125I)oPRL binding to rat liver microsomes in the presence of mAbs resulted in a decrease in the number of sites without changing the affinity of PRL binding by T1 and T6, whereas U5 and U6 altered neither parameter. (125I)mAb binding to rat liver microsomes was performed in the presence of various concentrations of unlabeled mAbs or oPRL to examine the interaction between mAbs. Competition of binding to the receptor was observed, respectively, between T1 and T6, U5 and U6, and U5 and E21 (a mAb to the rat liver PRL receptor previously produced). Both (125I)T1 and (125I)T6 binding were inhibited by oPRL, although not completely (80% inhibition at the higher concentrations). When (125I)T1 binding was analyzed by Scatchard analysis, two classes of binding sites to rat liver microsomes were found, of which only the number of higher affinity sites was affected by the presence of oPRL in incubation. Similar results were observed for (125I)T6 binding. (125I)mAb binding to microsomes from other tissues and species was examined. All five mAbs were able to bind to microsomes from rat tissues (liver, ovary, adrenal, prostate, and Nb2 lymphoma cells), similar to the level of (125I)oPRL binding in these tissues. The binding characteristics of (125I)T6 or (125I)U5 were essentially identical in all rat tissues examined.
Method for the radiohalogenation of proteins resulting in decreased thyroid uptake of radioiodine
A procedure is described for the radioiodination of proteins using an iodinated derivative of N-succinimidyl 3-(tri-n-butylstannyl) benzoate (ATE). Adequate removal of unreacted ATE from (/sup 125/I)ATE was necessary for optimal protein radioiodination. Labelling efficiencies of greater than 60% could be obtained after a 20 min incubation of goat IgG with (/sup 125/I)ATE at 4/sup 0/C. Paired-label experiments with goat IgG labeled with /sup 125/I using ATE and /sup 131/I using Iodogen demonstrated that use of the ATE reagent for protein labeling significantly reduced (P < 0.005) the thyroid uptake of radioiodine.
Pharmacokinetics of copolymers of N-vinylpyrrolidone with acrylic acid. Article 1
The authors studied the pharmacokinetics of the copolymers of n-vinyl-pyrrolidone (I) with acrylic acid (II) (copolymer III) using the radioactive isotope /sup 125/I. In experiments on mice, they studied the distribution of a copolymer of I with II (/sup 125/I-III) in the organism of the animals. The content of /sup 125/I-III and its possible radioactive metabolites in the blood and organs of mice after a single intravenous administration of the given preparation is shown. The radioactivity of organs after butanol extraction is presented.
The genetic probe labeled with positron emitter for monitoring tumor cells transfacted by herpes simplex virus thymidine kinase gene has been intensively studied. A useful synthetic methodology was developed to synthesize (E)-5-[2-(tributylstannyl)vinyl]arabinosyl uridine (TSVAU) and to radiolabel (E)-5-{2-[125I]iodovinyl}arabinosyl uridine (IVAU) substrate for herpes simplex virus type-1 thymidine kinase gene. The synthesis started from arabinosyl uridine via six steps to provide TSVAU in 18% yield. The subsequent radiolabeling with Na[125I]I under oxidation provided [125I]IVAU in 80% radiochemical yield.
Previously, our team used Monte Carlo simulation to demonstrate that a gamma camera could potentially be used as an online image guidance device to visualize seeds during permanent breast seed implant procedures. This could allow for intraoperative correction if seeds have been misplaced. The objective of this study is to describe an experimental evaluation of an online gamma-camera imaging of permanent seed implantation (OGIPSI) prototype. The OGIPSI device is intended to be able to detect a seed misplacement of 5 mm or more within an imaging time of 2 min or less. The device was constructed by fitting a custom built brass collimator (16 mm height, 0.65 mm hole pitch, 0.15 mm septal thickness) on a 64 pixel linear array CZT detector (eValuator-2000, eV Products, Saxonburg, PA). Two-dimensional projection images of seed distributions were acquired by the use of a digitally controlled translation stage. Spatial resolution and noise characteristics of the detector were measured. The ability and time needed for the OGIPSI device to image the seeds and to detect cold spots was tested using an anthropomorphic breast phantom. Mimicking a real treatment plan, a total of 52 {sup 103}Pd seeds of 65.8 MBq each were placed on three different layers at appropriate depths within the phantom. The seeds were reliably detected within 30 s with a median error in localization of 1 mm. In conclusion, an OGIPSI device can potentially be used for image guidance of permanent brachytherapy applications in the breast and, possibly, other sites.
Treatment of hammertoe deformity using a one-piece intramedullary device: a case series.
Hammertoes are common deformities that are often surgically treated using arthrodesis or arthroplasty of the proximal interphalangeal joint with percutaneous, temporary Kirschner wire fixation. However, percutaneous Kirschner wire fixation is associated with potential complications, including wire migration, breakage, and pin tract infection. Furthermore, the complications of pseudoarthrosis and nonunion are seen using this technique owing to a lack of rotational control of the Kirschner wire. Another drawback of this implant is the need for wire removal and the associated patient anxiety with this in-office procedure. In the present series of 7 toes in 3 patients, we describe an alternative method of hammertoe fixation using a permanently implanted, 1-piece intramedullary device used to stabilize the proximal interphalangeal interface. The potential advantages of this prosthesis include elimination of wire migration and breakage, enhanced control and stability of the digit, elimination of potential pin tract infection, and decreased patient anxiety since hardware removal is not required. The patients were followed up for approximately 1 year after the surgery, and no intraoperative or postoperative complications were observed. The implant maintained proper clinical and radiographic alignment throughout the observation period, without implant failure or breakage. All patients were satisfied with the cosmetic appearance of their surgically corrected toes and were able to perform all activities of daily living without the use of assistive devices. Also, their postoperative pain and function were acceptable. The implant used in the patients described in the present report appears to be a viable alternative for the treatment of hammertoe. PMID:22632839
Purpose: To assess toxicity and outcome following permanent iodine-125 seed implant as an adjunct to surgical resection in cases of advanced thoracic malignancy. Methods and Materials: An institutional review board-approved retrospective review was performed. Fifty-nine patients were identified as having undergone thoracic brachytherapy seed implantation between September 1999 and December 2006. Data for patient demographics, tumor details, and morbidity and mortality were recorded. Results: Fifty-nine patients received 64 implants. At a median follow-up of 17 months, 1-year and 2-year Kaplan-Meier rates of estimated overall survival were 94.1% and 82.0%, respectively. The 1-year and 2-year local control rates were 80.1% and 67.4%, respectively. The median time to develop local recurrence was 11 months. Grades 3 and 4 toxicity rates were 12% at 1 year. Conclusions: This review shows relatively low toxicity for interstitial planar seed implantation after thoracic surgical resection. The high local control results suggest that an incomplete oncologic surgery plus a brachytherapy implant for treating advanced thoracic malignancy merit further investigation.
The present study examined the ability of dual-chamber (DDD) pacing to improve symptoms and exercise tolerance in patients with non-obstructive hypertrophic cardiomyopathy (HNCM). Seven patients with HNCM who had failed to benefit from pharmacotherapy participated in the study. The New York Heart Association (NHYA) functional class status and exercise tolerance, which was determined by the treadmill exercise test, were recorded and an echocardiographic observation was performed before, and 1 week, 3 months and 1 year after the implantation of a permanent DDD pacemaker. The atrioventricular delay (AVd) was determined by measuring the point of peak rapid filling velocity and maximum cardiac output (CO). Two patients were not implanted with a permanent pacemaker because their CO and blood pressure decreased or because palpitation occurred during temporary pacing. The ratio between early and late peaks of flow velocity (1.56, 1.21, 0.95, and 0.86 before implantation and 1 week, 3 months and 1 year after implantation, respectively); deceleration time (ms: 263.2, 217.6, 204.6, 187.0); peak filling rate (ml/s: 146.2, 204.0, 233.2, 243.6); NYHA functional class status (2.0, 1.8, 1.6, 1.4); and exercise tolerance (s: 203, 264, 403, 480) were significantly improved after implantation. However, left ventricular dimension, percent fractional shortening, ejection fraction, acceleration time and the isovolumic relaxation time were not changed significantly. In conclusion, DDD pacing improved symptoms and the NYHA functional class status, which is associated with improvement of left ventricular diastolic function. It is proposed that DDD pacing would be useful in patients not only with obstructive but also non-obstructive hypertrophic cardiomyopathy refractory to medical treatment, depending on the careful selection of subjects. (Jpn Circ J 2001; 65: 283 - 288)
Complex Retrieval of Embedded IVC Filters: Alternative Techniques and Histologic Tissue Analysis
Purpose: We evaluated the safety and effectiveness of alternative endovascular methods to retrieve embedded optional and permanent filters in order to manage or reduce risk of long-term complications from implantation. Histologic tissue analysis was performed to elucidate the pathologic effects of chronic filter implantation. Methods: We studied the safety and effectiveness of alternative endovascular methods for removing embedded inferior vena cava (IVC) filters in 10 consecutive patients over 12 months. Indications for retrieval were symptomatic chronic IVC occlusion, caval and aortic perforation, and/or acute PE (pulmonary embolism) from filter-related thrombus. Retrieval was also performed to reduce risk of complications from long-term filter implantation and to eliminate the need for lifelong anticoagulation. All retrieved specimens were sent for histologic analysis. Results: Retrieval was successful in all 10 patients. Filter types and implantation times were as follows: one Venatech (1,495 days), one Simon-Nitinol (1,485 days), one Optease (300 days), one G2 (416 days), five Guenther-Tulip (GTF; mean 606 days, range 154-1,010 days), and one Celect (124 days). There were no procedural complications or adverse events at a mean follow-up of 304 days after removal (range 196-529 days). Histology revealed scant native intima surrounded by a predominance of neointimal hyperplasia and dense fibrosis in all specimens. Histologic evidence of photothermal tissue ablation was confirmed in three laser-treated specimens. Conclusion: Complex retrieval methods can now be used in select patients to safely remove embedded optional and permanent IVC filters previously considered irretrievable. Neointimal hyperplasia and dense fibrosis are the major components that must be separated to achieve successful retrieval of chronic filter implants.
Endocarditis and localized pocket infections are recognized as serious adverse events in patients with implanted cardiac impulse generators. We have undertaken a 10-y retrospective study in North Denmark Region (population 0.5 million) in order to elucidate the clinical spectrum, causative microorganisms, management and outcome. Infections associated with permanent pacemakers (PPM) and implanted cardioverter-defibrillator (ICD) devices were identified by searching hospital databases. Ninety-one incident cases were recorded in 1999 through 2008: 26 patients had endocarditis, 39 patients had a localized pocket infection, and 9 patients developed surgical sepsis with or without local signs immediately after implantation or reoperation; the device was the likely but unconfirmed focus of infection in 17 patients with bacteraemia. Staphylococcus aureus, coagulase-negative staphylococci and other Gram-positive bacteria were the predominant causative agents; only 6 cases were culture-negative. Management included device and lead extraction and individualized antibiotic therapy. The all-cause 30-day case-fatality was 11%. Only 3 recurrences were recorded during 2 y of follow-up. In conclusion, infections associated with permanent impulse generators have a broader clinical spectrum than often reported in the literature. Most cases are culture-positive with staphylococcal predominance. The short-term mortality is notably high, but the risk of recurrence is low. PMID:20465488
Purpose Atrial fibrillation (AF) is one of the major risk factors for ischemic stroke, and 90% of thromboembolisms in these patients arise from the left atrial appendage (LAA). Recently, it has been documented that an LAA occlusion device (OD) is not inferior to warfarin therapy, and that it reduces mortality and risk of stroke in patients with AF. Materials and Methods We implanted LAA-ODs in 5 Korean patients (all male, 59.8±7.3 years old) with long-standing persistent AF or permanent AF via a percutaneous trans-septal approach. Results 1) The major reasons for LAA-OD implantation were high risk of recurrent stroke (80%), labile international neutralizing ratio with hemorrhage (60%), and 3/5 (60%) patients had a past history of failed cardioversion for rhythm control. 2) The mean LA size was 51.3±5.0 mm and LAA size was 25.1×30.1 mm. We implanted the LAA-OD (28.8±3.4 mm device) successfully in all 5 patients with no complications. 3) After eight weeks of anticoagulation, all patients switched from warfarin to anti-platelet agent after confirmation of successful LAA occlusion by trans-esophageal echocardiography. Conclusion We report on our early experience with LAA-OD deployment in patients with 1) persistent or permanent AF who cannot tolerate anticoagulation despite significant risk of ischemic stroke, or 2) recurrent stroke in patients who are unable to maintain sinus rhythm. PMID:17598008
The role of insulin-induced receptor autophosphorylation in its internalization was analyzed by comparing {sup 125}I-labeled insulin ({sup 125}I-insulin) internalization in Chinese hamster ovary (CHO) cell lines transfected with normal (CHO.T) or mutated insulin receptors. In four cell lines with a defect of insulin-induced autophosphorylation, {sup 125}I-insulin internalization was impaired. By contrast, in CHO.T cells and in two other CHO cell lines with amino acid deletions or insertions that do not perturb autophosphorylation, {sup 125}I-insulin internalization was not affected. A morphological analysis showed that the inhibition is linked to the ligand-specific surface redistribution in which the insulin-receptor complexes leave microvilli and concentrate on nonvillous segments of the membrane where endocytosis occurs.
Evaluation of radioiodinated iodoclorgyline as a SPECT radiopharmaceutical for MAO-A in the brain
An in vivo estimation of the newly synthesized MAO-A specific inhibitor, [{sup 125}I]-labeledN -[3(2,4-dichloro-6-iodophenoxy)propyl]-N-methyl-2-propynylamine ([{sup 125}I]-iodoclorgyline), was performed. Retention of the radioactivity of this radioligand was observed in the brain from 1 h post-injection. Pretreatments with clorgyline and l-deprenyl showed selective binding of [{sup 125}I]-iodoclorgyline to MAO-A in the brain at 24 h post-injection. Moreover, a good correlation (r = 0.907) between the uptake of [{sup 125}I]-iodoclorgyline and MAO-A enzyme activity in the cortex was observed in the pretreatment study with several doses of clorgyline. Although improvement to increase the brain/blood ratio is desirable because of slow blood clearance of the radioactivity, radioiodinated iodoclorgyline may serve as a useful SPECT radiopharmaceutical for quantitative analysis of MAO-A in the brain.
Quinoxaline 1,4-dioxide derivative, 2-{[benzyl(cyanomethyl)amino]methyl}-3-(ethoxycarbonyl) quinoxaline 1,4-dioxide (Q3D), was synthesized and labeled with radioiodine via direct electrophilic substitution giving labeling yield above 90%. The product was examined by paper electrophoresis. 125I-Q3D was prepared using Chloramine T as oxidizing agent. 125I-Q3D was stable for up to 72 h post labeling, in contrast to 99m Tc-AQCD which is stable only for a short time. Biodistribution study of 125I-Q3D in ascites tumor bearing mice revealed large uptake of the labeled compound in tumor sites. In addition, in vitro incubation of the labeled compound with Ehrlich cells indicated incorporation of these compounds in DNA of tumor cells. This uptake of 125I-Q3D in DNA of tumor cells may be helpful in t...
Lysosomal delivery of ANP receptors following internalization in PC12 cell
Internalization and intracellular processing of ANP-B and C receptors play an important role in regulating cell responsiveness to atrial natriuretic peptides (ANP). Receptor internalization was indirectly monitored with [sup 125]I labelled ligand. When [sup 125]I-ANP(99-126) was internalized by the cells at 37[degrees]C, 55% of the internalized radioactivity was localized in the lysosomal fraction. When receptors were affinity-labelled with [sup 125]I-ANP(99-126) and allowed to internalize for varying time periods, two radiolabelled proteins in the m.wt. range of 56 and 52 KDa were detected in the cytosolic extract. These proteins appear to be the hydrolytic products of the ANP-C receptor expressed on the plasma membrane. In addition to lysosomal delivery, shedding of the ANP-C receptor from the cell surface was detected following incubation of cells with [sup 125]I-ANP(99-126). The dual processes may function to clear exogenous ANP from the extracellular compartments.
1. Acute inflammation was induced in rabbit skin by intradermal injection of arachidonic acid. 2. Inflammation was assessed by the local accumulation of intravenously-injected 125I-serum albumin (plasma extravasation) and histologically (polymorphonuclear leucocyte, PMNL infiltration). 3. Leukotrien...
The inflammatory response to Escherichia coli was quantitated in the skin of normal rabbits and the kinetics established as described previously. Hyperemia, measured with radiolabeled microspheres; vascular permeability, estimated with 125 I-albumin; and leukocyte infiltration, quantitated with 51Cr...
Monte-Carlo simulation of uncertainty in the estimation of 125I in the thyroid
At the Bhabha Atomic Research Centre, a thin (76 mm diameter x 2 mm thickness) NaI (Tl) detector is used for the assessment of 125I in the thyroid of the radiation workers engaged in the preparation of radio-immunoassay kits. The detector was calibrated using a REMCAL (radiation equivalent manikin calibration) phantom with a known amount of the 125I activity filled in its thyroidal cavity. Since 125I emits low-energy photons ranging from 27 to 35.4 keV, its detection efficiency depends on several parameters such as neck-to-detector distance, detector size, unknown tissue thickness overlying (OTT) the thyroid and the shape and size of the thyroid. To account for uncertainties introduced by these factors in the estimation of 125I, a computer program based on the Monte Carlo photon transport ...
Putative melatonin receptors in a human biological clock
In vitro autoradiography with /sup 125/I-labeled melatonin was used to examine melatonin binding sites in human hypothalamus. Specific /sup 125/I-labeled melatonin binding was localized to the suprachiasmatic nuclei, the site of a putative biological clock, and was not apparent in other hypothalamic regions. Specific /sup 125/I-labeled melatonin binding was consistently found in the suprachiasmatic nuclei of hypothalami from adults and fetuses. Densitometric analysis of competition experiments with varying concentrations of melatonin showed monophasic competition curves, with comparable half-maximal inhibition values for the suprachiasmatic nuclei of adults (150 picomolar) and fetuses (110 picomolar). Micromolar concentrations of the melatonin agonist 6-chloromelatonin completely inhibited specific /sup 125/I-labeled melatonin binding, whereas the same concentrations of serotonin and norepinephrine caused only a partial reduction in specific binding. The results suggest that putative melatonin receptors are located in a human biological clock.
Circulating monocytes bind /sup 125/I-insulin in a specific fashion and have been used to analyze the ambient receptor status in humans. When freshly isolated circulating monocytes are incubated with /sup 125/I-insulin and examined by electron microscopic autoradiography, approximately 18% of the labeled material is internalized after 15 minutes at 37 degrees C. By 2 hours at 37 degrees C, approximately one half of the /sup 125/I-insulin is internalized. Internalization occurs also at 15 degrees C but at a slower rate. Furthermore, the monocytes bind and internalize /sup 125/I-insulin in a manner that mirrors that of major target tissues, such as rat hepatocytes. These data suggest that the insulin receptor of the circulating monocyte might be regulated by adsorptive endocytosis in a manner analogous to that of target tissue, such as the liver.
Peptide YY is a highly potent emetic when given intravenously in dogs. We hypothesized that the area postrema, a small brain stem nucleus that acts as a chemoreceptive trigger zone for vomiting and lies outside the blood-brain barrier, might have receptors that PYY would bind to, in order to mediate the emetic response. We prepared (/sup 125/I)PYY and used autoradiography to show that high affinity binding sites for this ligand were highly localized in the area postrema and related nuclei of the dog medulla oblongata. Furthermore, the distribution of (/sup 125/I)PYY binding sites in the rat medulla oblongata was very similar to that in the dog; the distribution of (/sup 125/I)PYY binding sites throughout the rat brain was seen to be similar to the distribution of (/sup 125/I)NPY binding sites.
Although several COX-2 inhibitors have recently been radiolabeled, their potential for imaging COX-2 expression remains unclear. In particular, the sulfonamide moiety of COX-2 inhibitors may cause slow blood clearance of the radiotracer, due to its affinity for carbonic anhydrase (Canada) in erythrocytes. Thus, we designed a methyl sulfone-type analogue, 5-(4-iodophenyl)-1-[4-(methylsulfonyl)phenyl]-3-trifluoromethyl-1H-pyrazole (IMTP). In this study, the potential of radioiodinated IMTP was assessed in comparison with a {sup 125}I-labeled celecoxib analogue with a sulfonamide moiety ({sup 125}I-IATP). Methods: The COX inhibitory potency was assessed by measuring COX-catalyzed oxidation by hydrogen peroxide. The biodistribution of {sup 125}I-IMTP and {sup 125}I-IATP was determined by the ex vivo tissue counting method in rats. Distribution of the labeled compounds to rat blood cells was measured. Results: The COX-2 inhibitory potency of IMTP (IC{sub 5}=5.16 {mu}M) and IATP (IC{sub 5}=8.20 {mu}M) was higher than that of meloxicam (IC{sub 5}=29.0 {mu}M) and comparable to that of SC-58125 (IC{sub 5}=1.36 {mu}M). The IC{sub 5} ratios (COX-1/COX-2) indicated the high isoform selectivity of IMTP and IATP for COX-2. Significant levels of {sup 125}I-IMTP and {sup 125}I-IATP were observed in the kidneys and the brain (organs known to express COX-2). The blood clearance of {sup 125}I-IMTP was much faster than that of {sup 125}I-IATP. Distribution of {sup 125}I-IATP to blood cells (88.0%) was markedly higher than that of {sup 125}I-IMTP (18.1%), which was decreased by CA inhibitors. Conclusions: Our results showed a high inhibitory potency and selectivity of IMTP for COX-2. The substitution of a sulfonamide moiety to a methyl sulfone moiety effectively improved the blood clearance of the compound, indicating the loss of the cross reactivity with CA in {sup 125}I-IMTP. {sup 123}I-IMTP may be a potential SPECT radiopharmaceutical for COX-2 expression.
Predictors of permanent pacemaker implantation after Medtronic CoreValve bioprosthesis implantation.
AIMS: High-grade conduction disturbances requiring permanent pacemaker (PPM) implantation occur in up to 40% of patients following transcatheter aortic valve implantation (TAVI). The aim of this study was to identify pre-operative risk factors for PPM implantation after TAVI with the Medtronic CoreValve prosthesis (CVP).METHODS AND RESULTS: We retrospectively analysed 109 patients following transfemoral CVP implantation performed between 2008 and 2009 at the Leipzig Heart Center. Patients who had indwelling PPM at the time of TAVI (n = 21) were excluded, leaving 88 patients for analysis. Mean age was 80.3 ± 6.6 years and logistic EuroScore predicted risk of mortality was 23.3 ± 12.1%. A total of 32 patients (36%) underwent PPM implantation post-TAVI during the same hospital admission. A total of 27/88 (31%) had evidence of pre-operative abnormal conduction, including first degree AV block and left bundle brunch block. Statistically significant risk factors for the need for post-operative PPM were patient age >75 years [P = 0.02, odds ratio (OR) 4.6], pre-operative heart rate 4 mm (P = 0.03, OR 2.8), CVP prosthesis >26 mm (OR 2.2), atrial fibrillation (P = 0.001, OR 5.2), and ventricular rate <65 b.p.m. at the first post-operative day (P = 0.137, OR 6.0).CONCLUSION: PPM implantation occurs frequently after transfemoral TAVI with the CVP. Older age, chronic atrial fibrillation, pre-operative bradycardia, and larger or significantly oversized prostheses were independent risk factors for PPM implantation following TAVI with the CVP. PMID:22733983
Improved performance of waste water radiation monitor
Gamma ray waste water radiation monitor has been improved by using multichannel analyzer. Maximum permissible concentrations of /sup 125/I are one thousandth lower than /sup 51/Cr. Above this condition, the radioactive waste water cannot be pumped out occasionally. Gamma ray energy spectrum is measured by microcomputer based multichannel analyzer by which /sup 125/I photo-peak counts is separated from other radionuclide counts. Also detecting vessel is washed with pressured fresh water to prevent contamination.
The bioavailability, distribution, and metabolic fate of /sup 125/I-labeled insulin complexed to antibodies in guinea pig antiserum, purified guinea pig IgG1, IgG2, a mixture of IgG1 and IgG2, and homologous Lou/m rat antiserum were studied in inbred Lewis rats. /sup 125/I-insulin complexed to purified guinea pig IgG2 antibodies was rapidly cleared from the blood and sequestered in increasing amounts with time in the liver. Large amounts of the /sup 125/I-insulin complexed to guinea pig IgG1 antibodies remained in the blood for at least 30 min. The bioavailability of /sup 125/I-insulin bound to IgG1 and IgG2 antibodies was inhibited for at least 30 min because significantly less was available for rapid binding to insulin receptors on hepatocytes and renal tubular cells and its subsequent rapid degradation. The bioavailability of /sup 125/I-insulin was further decreased when bound to antibodies in native guinea pig antiserum or a mixture of IgG1 and IgG2 antibodies compared with the /sup 125/I-insulin complexed to either purified IgG1 or IgG2 antibodies alone. The /sup 125/I-insulin bound to antibodies in native guinea pig antiserum or a mixture of IgG1 and IgG2 antibodies was distributed in vivo in a manner reflecting the relative concentrations of the IgG1 and IgG2 antibodies present. The bioavailability, distribution, and metabolic fate of /sup 125/I-insulin in immune complexes prepared with homologous Lou/m rat insulin antiserum was qualitatively similar to that observed with immune complexes prepared with guinea pig insulin antiserum. It appears that the Lewis rat can be used as an in vivo model to study the bioavailability,distribution,and metabolic fate of insulin bound to xenogenic or homologous insulin antibodies.
Study of Radioiodine Sorption and Diffusion on Minerals
In this paper, the performance of adsorbing and retarding 125I (substituted for 129I) for mixed minerals as buffer, backfill material was investigated. The distribution coefficient Kds by batch sorption experiments were determined for four kinds of minerals and one kind of bentonite under atmosphere. Sorption and desorption of radioiodine on several minerals were studied under low oxygen ambience at first time in the domestic, and apparent diffusion coefficient Da of 125I- was determined for mixed minerals under atmosphere. The results as follows: Distribution coefficient Kds of 125I- under atmosphere: bentonite is 3.23 ml{center_dot}g-1 , chalcopyrite is 72.42 ml{center_dot}g-1 , galena is 118.9 ml{center_dot}g-1 , pyrite is 1.93 ml{center_dot}g-1 , cinnabar is 55.48 ml{center_dot}g-1 , and the corresponding Kds under low oxygen ambience: galena is 88.48 ml{center_dot}g-1 , chalcopyrite is 6.47 ml{center_dot}g-1 . when pH of solution was in the range of 2.25-12.26, Kds of 125I- on chalcopyrite , galena, pyrite and cinnabar decreased with increase of pH under atmosphere. Kds of 125I- on several minerals increased with increase of mineral ratio in mixed materials under atmosphere. Under the same condition, Kds of 125I- on chalcopyrite and galena were larger than Kds of 125IO3 -. Sorption of 125I- on galena seems to be irreversible. Apparent diffusion coefficient Da of 125I- in the mixed material was measured by the flow-through diffusion way, Da values under atmosphere was given: Da=7.29 x 10-12 m2{center_dot}s-1 .
Characterization, solubilization and partial purification of serotonin 5-HT1C receptors
/sup 125/I-Lysergic acid diethylamide (/sup 125/I-LSD) binds with high affinity to a unique serotonergic site on rat choroid plexus. These sites were localized to choroid plexus epithelial cells using a novel high resolution autoradiographic technique. In membrane preparations, the serotonergic site density was 3100 fmol/mg protein, which is 10 fold higher than the density of any other serotonergic site in brain homogenates. The pharmacology of this site, termed the 5-HT1c site, does not match that of 5-Ht1a, 5-HT1b or 5HT2 serotonergic sites. 5-Ht1c sites were solubilized from pig choroid plexus using the zwitterionic detergent, CHAPS. High affinity labelling of the solubilized site was obtained using the serotonergic radioligand, N1-methyl-2-(/sup 125/I)lysergic acid diethylamide (/sup 125/I-MIL). Choroid plexus tumors obtained from transgenic mice were examined for the presence of serotonin 5-HT1c receptors. /sup 125/I-LSD binding to choroid plexus tumors displays a pharmacological profile that matches the properties of 5-HT1c receptors in normal choroid plexus. The tumor exhibits the highest site density of serotonin receptors (6600 fmol/mg protein) found in any tissue. /sup 125/I-LSD autoradiography of brain sections from transgenic mice shows high levels of specific labelling over the tumor. The affinities of various indolealkyl, phenlakyl and beta-carboline derivatives for the serotonin 5-HT1c receptor were measured in pig choroid plexus using /sup 125/I-MIL. Serotonin precursors and metabolites were all very weak inhibitors of specific /sup 125/I-MIL binding. Structure-affinity relationships were determined for a number of indolealkylamine analogues. Only serotonin is present in cerebrospinal fluid at concentrations near its 5-HT1c inhibition constant, suggesting that serotonin is the natural 5-HT1c agonist.
The human platelet contains a functional 5-hydroxytryptamine (5-HT) receptor that appears to resemble the 5-HT2 subtype. In this study, we have used the iodinated derivative (125I)iodolysergic acid diethylamide ((125I)iodoLSD) in an attempt to label 5-HT receptors in human platelet and frontal cortex membranes under identical assay conditions to compare the sites labelled in these two tissues. In human frontal cortex, (125I)iodoLSD labelled a single high-affinity site (KD = 0.35 +/- 0.02 nM). Displacement of specific (125I)iodoLSD binding indicated a typical 5-HT2 receptor inhibition profile, which demonstrated a significant linear correlation (r = 0.97, p less than 0.001, n = 17) with that observed using (3H)ketanserin. However, (125I)iodoLSD (Bmax = 136 +/- 7 fmol/mg of protein) labelled significantly fewer sites than (3H)ketanserin (Bmax = 258 +/- 19 fmol/mg of protein) (p less than 0.001, n = 6). In human platelet membranes, (125I)iodoLSD labelled a single site with affinity (KD = 0.37 +/- 0.03 nM) similar to that in frontal cortex. The inhibition profile in the platelet showed significant correlation with that in frontal cortex (r = 0.96, p less than 0.001, n = 16). We conclude that the site labelled by (125I)iodoLSD in human platelet membranes is biochemically similar to that in frontal cortex and most closely resembles the 5-HT2 receptor subtype, although the discrepancy in binding capacities of (125I)iodoLSD and (3H)ketanserin raises a question about the absolute nature of this receptor.
Microchemical synthesis of the serotonin receptor ligand, /sup 125/I-LSD
The synthesis and properties of 2-(/sup 125/I)-lysergic acid diethylamide, the first /sup 125/I-labeled serotonin receptor ligand, are described. A novel microsynthesis apparatus was developed for this synthesis. The apparatus employs a micromanipulator and glass micro tools to handle microliter to nanoliter volumes on a microscope stage. This apparatus should be generally useful for the synthesis of radioligands and other compounds when limited amounts of material must be handled in small volumes.
Characterization of a tachykinin peptide NK2 receptor transfected into murine fibroblast B82 cells.
Membranes isolated from a murine fibroblast B82 cell line (SKLKB82#3) transfected with the bovine stomach cDNA pSKR56S exhibited binding of [His(125I)1]neurokinin A (125I-NKA) to a single population of sites with a Bmax of 147 fmol/mg of protein and a Kd of 0.59 nM. Control cell lines had little or ...
Pharmacokinetics of erythropoietin in intact and anephric dogs
The present studies were performed to determine the pharmacokinetic parameters of erythropoietin in intact and anephric dogs by use of unlabeled crude native erythropoietin (nEp) and iodine 125-labeled purified recombinant erythropoietin (rEp) given by intravenous infusion for 15 minutes. Sephadex G-75 gel filtration was used to confirm that the 125I-rEp molecule remained iodinated in dog plasma during the 24-hour period of these studies. The plasma disappearance of erythropoietin conformed to a biexponential equation for both nEp and 125I-rEp, with the central compartment being larger than the peripheral compartment. The mean distribution half-life of 75.3 +/- 21.2 minutes for nEp was significantly (p less than 0.05) longer than that of 125I-rEp (23.7 +/- 5.0 minutes) in intact dogs. The intercompartmental clearance (CIic) for nEp (0.018 +/- 0.006 L/kg/hr) was significantly smaller than that of 125I-rEp (0.068 +/- 0.018 L/kg/hr) in intact dogs (p less than 0.05). There were no significant differences in apparent volume of distribution, elimination half-life, and elimination clearance (CIe) for nEp and rEp in intact dogs. The mean elimination half-life for 125I-rEp in intact dogs (9.0 +/- 0.6 hours) and anephric dogs (13.8 +/- 1.4 hours) was significantly different (p less than 0.05). The CIe for 125I-rEp in anephric dogs (0.008 +/- 0.001 L/kg/hr) was significantly (p less than 0.05) smaller than that of 125I-rEp in intact dogs (0.011 +/- 0.001 L/kg/hr). There were no significant differences in apparent volume of distribution, distribution half-life, and CIic for 125I-rEp in intact and anephric dogs.
Plasma clearance of human extracellular-superoxide dismutase C in rabbits
Extracellular-superoxide dismutase (EC-SOD) is heterogenous in the vasculature with regard to heparin affinity and can be separated into three fractions: A, without affinity; B, with weak affinity; and C, with relatively strong heparin affinity. The plasma clearance of intravenously injected 125I-labeled and unlabeled human EC-SOD C was studied in rabbits. About 90% of injected 125I-EC-SOD C was eliminated from the blood within 5-10 min. Injection of heparin after 10 or 20 min led to an immediate release of all sequestered 125I-EC-SOD C back to the blood plasma. Later injections of heparin led to diminished release, although release could still be demonstrated after 72 h. A half-time of approximately 10 h could be calculated for heparin-releasable 125I-EC-SOD C. Unlabeled EC-SOD C, determined as enzymic activity and with ELISA, was likewise sequestered and released to the same degree as 125I-labeled EC-SOD C by heparin as tested at 20 min and 5 h. The immediacy of the heparin-induced release indicates that the sequestered enzyme had been bound to endothelial cell surfaces. The length of the half-time suggests that the putative cell surface binding has a physiological function and is not primarily a step in enzyme degradation. The distribution of sequestered 125I-labeled EC-SOD C to different organs was determined at times between 10 min and 24 h. Of the organs, the liver contained the most 125I-EC-SOD C, followed by kidney, spleen, heart, and lung. At all investigated times, the content in the analyzed organs was nearly as large as the amount that could be promptly released to plasma by intravenous heparin. This indicates that almost all 125I-EC-SOD C in the organs was present on endothelial cell surfaces and was not bound by other tissue cell surfaces, or was present within the cells.
The purpose of this study was to delineate the traffic patterns of EGF and EGF receptors (EGFR) in primary cultured acinar epithelial cells from rabbit lacrimal glands. Uptake of [(125)I]-EGF exhibited saturable and non-saturable, temperature-dependent components, suggesting both receptor-mediated and fluid phase endocytosis. Accumulation of [(125)I] was time-dependent over a 120-min period, but the content of intact [(125)I]-EGF decreased after reaching a maximum at 20 min. Analytical fractionation by sorbitol density gradient centrifugation and phase partitioning indicated that within 20 min at 37 degrees C [(125)I] reached an early endosome, basal-lateral recycling endosome, pre-lysosome, and lysosome. Small components of the label also appeared to reach the Golgi complex and trans-Golgi network. Intact [(125)I]-EGF initially accumulated in the recycling endosome; the content in the recycling endosome subsequently decreased, and by 120 min increased amounts of [(125)I]-labeled degradation products appeared in the pre-lysosomes and lysosomes. Confocal microscopy imaging of FITC-EGF and LysoTrackerRed revealed FITC enriched in a dispersed system of non-acidic compartments at 20 min and in acidic compartments at 120 min. Both confocal immunofluorescence microscopy and analytical fractionation indicated that the intracellular EGFR pool was much larger than the plasma membrane-expressed pool at all times. Cells loaded with [(125)I]-EGF released a mixture of intact EGF and [(125)I]-labeled degradation products. The observations indicate that in lacrimal acinar cells, EGFR and EGF-EGFR complexes continually traffic between the plasma membranes and a system of endomembrane compartments; EGF-stimulation generates time-dependent signals that initially decrease, then increase, EGF-EGFR traffic to degradative compartments. PMID:14978740
Transglutaminase (TGase) substrates monodansyl cadaverine (MDC, monodansyl-1,5 diaminopentane) and methylamine (MA) and polyamines (PA) were tested for their effects on the cellular processing of radioiodinated human follicle-stimulating hormone (/sup 125/I-hFSH). Specifically bound /sup 125/I-hFSH that could be released from cells during 10-min incubation period with acidified (pH 3.9) Hanks balanced-salt solution was considered membrane-bound unsequestered hormone. The rate at which cells sequestered /sup 125/I-hFSH into cellular compartments resistant to acid dissociation depended on the length of time in which cells were incubated with hormone. Cells incubated with /sup 125/I-hFSH for 15, 60, and 120 min had half-lives of sequestration of 26, 55 and 67 min respectively. One hundred-micromolar MDC inhibited degradation of /sup 125/I-hFSH as measured by the presence of radioactivity in the medium that was soluble in trichloroacetic acid. The rate of sequestration was never slower than that of controls, indicating that MDC did not decrease the ability of Sertoli cells to sequester /sup 125/I-hFSH. Despite these two observations, radioactivity associated with cells (acid-resistant radioactivity) was lower in cells treated with MDC than in controls. No effect of MDC on specific binding of 125I-hFSH was observed. Similar results were observed with MA, albeit at higher levels (0.0025-0.0425 M), consistent with their relative potency to inhibit TGase activity. Polyamines, spermine, and putrescine also decreased cell-associated radioactivity despite decreasing degradation of hFSH. TGase substrates (MDC, MA, PA) prevented entry of sequestered 125I-hFSH into the degradative pathways of Sertoli cells. These data suggest that transglutamination may influence the fate of sequestered FSH in Sertoli cells but not the rate at which sequestration occurs.
Evidence for multiple pathways of sup 125 I-insulin internalization in isolated rat hepatocytes
Insulin internalization has been characterized frequently as occurring by the coated pit pathway of receptor-mediated endocytosis. The present study in rat hepatocytes demonstrates that insulin internalization is, in part, receptor-mediated, but also occurs by nonreceptor-mediated or fluid-phase endocytosis. Endocytosis was probed with four perturbations: depletion of metabolic energy with anoxia, inhibition of endocytosis with phenylarsine oxide, disruption of coated pits with hyperosmolar sucrose, and inhibition of receptor recycling or ligand-receptor dissociation with monensin. Internalization of {sup 125}I-epidermal growth factor and {sup 125}I-asialofetuin was compared to {sup 125}I-insulin internalization. Pretreatment of cells with anoxia or hyperosmolarity inhibited {sup 125}I-insulin internalization by 40%; pretreatment with phenylarsine oxide resulted in inhibition by 54%. Monensin has no effect on uptake or degradation of a high insulin concentration, but inhibited degradation of a low insulin concentration resulting in intracellular accumulation of insulin. In contract, all four perturbations inhibited {sup 125}I-asialofetuin internalization by greater than 90%. Phenylarsine oxide almost completely abolished {sup 125}I-epidermal growth factor uptake; the other perturbations caused partial inhibition. Competition studies demonstrated that insulin internalization was receptor-mediated over a wide concentration range.
Autoradiographic localization of atrial natriuretic peptide receptor subtypes in rat kidney
The distribution of atrial natriuretic peptide (ANP) clearance receptors in rat kidney was investigated by in vitro autoradiography using des(Gln18,Ser19,Gly20,Leu21,Gly22)-ANP-(4- 23) (C-ANP) and 125I-Tyr0-ANP-(5-25) as relatively specific ligands of this receptor. Alpha-125I-ANP (100 pM) bound reversibly but with high affinity to glomeruli, outer medullary vasa recta bundles, and inner medulla. C-ANP (10 microM) inhibited greater than 60% of this glomerular binding but did not inhibit the binding of alpha-125I-ANP to medullary tissues. Alpha-125I-ANP also bound reversibly to the renal arteries up to the glomerulus. This arterial binding was only partly inhibited by 10 microM C-ANP. In the presence of 10 microM C-ANP, increasing concentrations of alpha-125I-ANP bound to a residue of glomerular sites with apparent dissociation constants of 0.82 +/- 0.16 to 2.73 +/- 1.20 nM at different cortical levels. 125I-Tyr0-ANP-(5-25) bound significantly to glomeruli and intrarenal arteries but not to vasa recta bundles or inner medulla. This glomerular binding also occurred with nanomolar dissociation constants. It was completely inhibited by 1 microM alpha-ANP and 10 microM C-ANP, but not by unrelated peptides such as gastrin. These results suggest that renal ANP clearance receptors are restricted in vivo to the glomeruli and renal arterial system of the rat.
The {omega}-conotoxin GVIA (CTX) receptor has been purified 1,900-fold to apparent homogeneity by monitoring both reversible binding of {sup 125}I-labeled CTX ({sup 125}I-CTX) and photoincorporation of N-hydroxysuccinimidyl-4-azidobenzoate-{sup 125}I-CTX (HSA-{sup 125}I-CTX). Photoincorporation of HSA-{sup 125}I-CTX into a 230-kDa protein exhibits a pharmacologic and chromatographic profile indicating that the 230-kDa protein is the CTX-binding subunit of the receptor. The pharmacologic specificity of {sup 125}I-CTX binding to the purified CTX receptor closely resembles that of the native membrane-bound form with respect to sensitivity towards CTX and other peptide toxin antagonists. The purified CTX receptor comprises the 230-kDa protein ({alpha}{sub 1}) and four additional proteins with apparent molecular masses of 140 ({alpha}{sub 2}), 110, 70 ({beta}{sub 2}), and 60({beta}{sub 1}) kDa. This subunit structure closely resembles that of the 1,4-dihydropyridine-sensitive L-type calcium channel.
/sup 125/I-Lysergic acid diethylamide (/sup 125/I-LSD) is the first /sup 125/I-labeled ligand for serotonin receptor studies. Its binding to rat frontal cortex membranes is saturable, reversible, and stereospecific. Specific binding is linearly dependent on tissue concentration and represents 70-80% of the total binding. Scatchard plots of the binding data are linear with a KD of 1.5 nM, a Bmax of 12.4 fmol/mg wet weight tissue, and a Hill slope of 1.02. The binding kinetics are highly temperature-dependent. At 37 degrees C the bimolecular association rate constant is 1.28 X 10(8) min-1 M-1 and the dissociation rate constant is 0.087 min-1 (t 1/2 . 8.0 min). At 0 degrees C less than 4% dissociation occurs over 40 min and the association rate is similarly depressed. Inhibition of /sup 125/I-LSD binding by a variety of serotonergic, dopaminergic, and adrenergic ligands reveals a 5-hydroxytryptamine2 (5-HT2) serotonergic profile for this binding site. Regional distribution studies of /sup 125/I-LSD binding in rat brain show that areas with the highest levels of binding include the cortex and striatum. Iodinated radioligands can be synthesized with specific activities exceeding 2,000 Ci/mmol, which makes them approximately 75-fold more sensitive than tritiated radioligands. This high specific activity, coupled with the selectivity of /sup 125/I-LSD for 5-HT2 sites, makes this ligand a sensitive new probe for 5-HT2 serotonin receptors.
Rat liver microsomes were labeled with the hydrophobic photoactivable reagent (/sup 125/I)TID. /sup 125/I-incorporation into 3-methylcholanthrene (3-MC)- and phenobarbital (PB)-induced microsomal protein was enhanced 5- and 8-fold, respectively, relative to the incorporation into uninduced liver microsomes. The major hepatic P-450 forms inducible by PB and 3-MC (P-450 PB-4 and P-450 BNF-B, respectively) were shown to be the principal polypeptides labeled by (/sup 125/I)TID in the correspondingly induced microsomes. Extensive trypsin cleavage of (/sup 125/I)TID-labeled microsomal P-450 PB-4 yielded a single labeled peptide of M/sub r/ approx. 4000. (/sup 125/I)TID incorporation into microsomal P-450 PB-4 was fully inhibited by the P-450 PB-4 substrate benzphetamine (1mM). Unactivated TID was shown to be an effective inhibitor of P-450-dependent 7-ethoxycoumarin O-deethylation catalyzed by PB-induced liver microsomes (IC/sub 50/ = 10..mu..M at 120..mu..M substrate). TID inhibited purified, reconstituted P-450 PB-4 with kinetics consistent with either competitive or mixed inhibition and a Ki of 2..mu..M. These findings indicate that TID is an active site-directed inhibitor of this hemeprotein and suggest that (/sup 125/I)TID may serve as a useful probe for the substrate binding site of rat hepatic P-450 PB-4.
In vivo binding of (/sup 125/I)-2-(beta-(3-iodo-4-hydroxyphenyl)ethylaminomethyl tetralone) ((/sup 125/I)HEAT) to alpha-1 adrenoceptors in the rat brain was determined over 4 hr. Uptake in the thalamus and frontal cortex was approximately 0.1% injected dose per gram tissue. Thalamus/cerebellum ratios of 10:1 and frontal cortex/cerebellum ratios of 5:1 were found at 4 hr. Pretreatment with prazosin, an alpha-1 antagonist, completely inhibited the accumulation of (/sup 125/I)HEAT in thalamus and frontal cortex; yet uptake of radioactivity was not significantly affected by antagonists and agonists for other receptors classes (propranolol, beta-1; apomorphine, D-1; spiperone, D-2). Binding of (/sup 125/I)HEAT is saturable. At 4 hr, (/sup 125/I)HEAT or (/sup 123/I)HEAT was shown to be the only radioactive material in rat thalamus and frontal cortex. Iodine-123 HEAT and (/sup 125/I)HEAT were synthesized as radiopharmaceuticals within 3 hr in 99% radiochemical purity.
In order to simulate the distribution and elimination of radioiodinated human beta-endorphin (/sup 125/I-beta-EP) after iv bolus injection in rats, we proposed a physiologically based pharmacokinetic model incorporating diffusional transport of /sup 125/I-beta-EP across the capillary membrane. This model assumes that the distribution of /sup 125/I-beta-EP is restricted only within the blood and the tissue interstitial fluid, and that a diffusional barrier across the capillary membrane exists in each tissue except the liver. The tissue-to-blood partition coefficients were estimated from the ratios of the concentration in tissues to that in arterial plasma at the terminal (pseudoequilibrium) phase. The total body plasma clearance (9.0 ml/min/kg) was appropriately assigned to the liver and kidney. The transcapillary diffusion clearances of /sup 125/I-beta-EP were also estimated and shown to correlate linearly with that of inulin in several tissues. Numerically solving the mass-balance differential equations as to plasma and each tissue simultaneously, simulated concentration curves of /sup 125/I-beta-EP corresponded well with the observed data. It was suggested by the simulation that the initial rapid disappearance of /sup 125/I-beta-EP from plasma after iv injection could be attributed in part to the transcapillary diffusion of the peptide.
/sup 125/I-Calmodulin is internalized by isolated rat renal brush border membrane vesicles (BBV) in a time, temperature and calcium dependent manner. Internalization of /sup 125/I-calmodulin into the osmotically sensitive space of BBV was distinguished from binding of the ligand to the outer BBV surface by examining the interaction of ligand and BBV at different medium osmolarities (300-1100 mosm), uptake was inversely proportional to medium osmolarity. Internalized /sup 125/I-calmodulin was intact and Western blots of solubilized BBV with /sup 125/I-calmodulin demonstrated the presence of several calmodulin-binding proteins of 143, 118, 50, 47.5, 46.5 and 35 kilodaltons which could represent potential intravesicular binding sites for the ligand. Heparin and the related glycosaminoglycan heparin sulfate both showed a dose-dependent inhibition (0.5-50 ..mu..g/ml) of /sup 125/I-calmodulin uptake by BBV, but other sulfated and nonsulfated glycosaminoglycans including chondroitin sulfates, keratan sulfate and hyaluronic acid showed little or no inhibitory effect. Desulfation of heparin virtually abolished the inhibition of uptake while depolymerization reduced it. Heparin did not block the binding of /sup 125/I-calmodulin to BBV proteins as assessed by Western blotting technique suggesting its effect was on internalization of the ligand rather than on its association with internal membrane proteins.
The membrane characteristics controlling {sup 125}I and {sup 36}Cl transport across anion exchange paper membranes are examined using four different ion exchange capacities paper membranes treated with trimethylhydroxypropylamino group. Non-equilibrium thermodynamic analyses for the paper membrane transport process are carried out based on transmembrane potential, membrane conductance, and ion flux measurements. The electroconductive membrane, permeabilities representing the solution/membrane ion distribution due to electrostatic effects, and the diffusional membrane permeabilities, representing the migration speed of ions within the membrane phase, for {sup 125}I are higher than those for {sup 36}Cl in all cases. In the paper membrane treated with trimethylhydroxypropylamino group, {sup 125}I diffusion or {sup 125}I solution/membrane distribution process can be improved by increasing the concentration of anion exchange sites in the paper membrane. These findings indicate the potential utility of paper membranes prepared in this way for separating {sup 125}I from radioactive waste that has been contaminated with chloride ions. The {sup 125}I transport performance of such systems may be improved with the use of other anion-exchange groups. (author)
Three different monoiodinated radioligands of alpha-MSH (alpha-melanocyte-stimulating hormone) were compared in a binding assay with human D10 melanoma cells: (Tyr(125I)2)-alpha-MSH, (Tyr(125I)2,NIe4)-alpha-MSH, and (Tyr(125I)2,NIe4,D-Phe7)-alpha-MSH. They were prepared either by the classical chloramine T method or by the Enzymobead method. A simple and rapid purification scheme was developed consisting of a primary separation on reversed-phase C18 silica cartridges immediately after the iodination, followed by HPLC purification before each binding experiment. Biological testing of the three radioligands showed that they all retained high melanotropic activity in the B16 melanin assay and the Anolis melanophore assay. However, in human D10 melanoma cells, (Tyr(125I)2,NIe4)-alpha-MSH led to a high degree of non-specific binding to the cells which could not be displaced by excess alpha-MSH and only partially by (NIe4)-alpha-MSH. The (Tyr(125I)2,NIe4,D-Phe7)-alpha-MSH tracer gave similar results but with a much lower proportion of non-specific binding. On the other hand, (Tyr(125I)2)-alpha-MSH proved to be an excellent radioligand whose non-specific binding to the D10 cells was not higher than 20% of the total binding.
Glomerular mesangium: kinetics using radiolabeled ferritin and the effects of aggregated IgG. [Rats
A quantitative method for studying glomerular mesangial kinetics using radiolabeled native ferritin (/sup 125/I-NF) is described. Groups of Sprague-Dawley rats were given injections of monomeric /sup 125/I-NF in a dose of 10 mg/100 g and sacrificed at 4, 16, and 36 hr. Radioactivity was measured in preparations of isolated glomeruli, spleen, and liver, and in blood. After initial uptake, a progressive decrease in the concentration of /sup 125/I-NF was observed in the mesangium and other organs. To examine the effect of one macromolecule on the mesangial kinetics of NF a separate group of animals was given aggregated human IgG (AHIgG) (40 mg/100 g) 4 hr prior to administration of /sup 125/I-NF. The administration of AHIgG did not alter the kinetics of /sup 125/I-NF in the mesangium, plasma, or spleen but the disappearance of /sup 125/I-NF from the liver was accelerated. Although the cellular mechanisms for uptake of NF and AHIgG are different, the presence of one macromolecule (AHIgG) within the mesangium did not affect the uptake and disappearance of another (NF). Thus, the glomerular mesangium has a relatively high capacity under normal circumstances.
PurposeExternal-beam radiation therapy combined with low-doserate permanent brachytherapy are commonly used to treat men with localized prostate cancer. This Phase II trial was performed to document late gastrointestinal or genitourinary toxicity as well as biochemical control for this treatment in a multi-institutional cooperative group setting. This report defines the long-term results of this trial. Methods and MaterialsAll eligible patients received external-beam radiation (45 Gy in 25 fractions) followed 2-6 weeks later by a permanent iodine 125 implant of 108 Gy. Late toxicity was defined by the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme. Biochemical control was defined by the American Society fo...
Transperineal permanent prostate brachytherapy is a safe and efficacious treatment option for patients with organ-confined prostate cancer. Careful adherence to established brachytherapy standards has been shown to improve the likelihood of procedural success and reduce the incidence of treatment-related morbidity. A collaborative effort of the American College of Radiology (ACR) and American Society for Therapeutic Radiation Oncology (ASTRO) has produced a practice guideline for permanent prostate brachytherapy. The guideline defines the qualifications and responsibilities of all the involved personnel, including the radiation oncologist, physicist and dosimetrist. Factors with respect to patient selection and appropriate use of supplemental treatment modalities such as external beam radiation and androgen suppression therapy are discussed. Logistics with respect to the brachtherapy implant procedure, the importance of dosimetric parameters, and attention to radiation safety procedures and documentation are presented. Adherence to these practice guidelines can be part of ensuring quality and safety in a successful prostate brachytherapy program.
Sacral nerve stimulation in the elderly
Abstract Aim- Increasing life expectancy will increase the number of elderly patients with faecal incontinence. The study aimed to assess the safety and efficacy of sacral nerve stimulation (SNS) in patients over the age of 65-years. Method- Patients aged over 65-years, who underwent temporary SNS from 1996 for faecal incontinence unresponsive to conservative treatment, were followed prospectively. Results- Between January 1996 and December 2009, 30 patients [mean age 69.3-years (SD, 3.4)] underwent temporary SNS. Twenty-three (77%) had a >50% improvement in the St Mark-s Continence Score and progressed to permanent SNS implantation. Their mean (SD) score increased from 19 (3.2) at baseline to 8 (3.4) during temporary SNS and to 9 (3.4) 3-months after permanent SNS and 10 (3.7) at the late...
Paradoxical Peripheral Embolism Coincident with Acute Pulmonary Thromboembolism
Paradoxical embolism may occur in patients with acute pulmonary thromboembolism, when patent foramen ovale (PFO) coexists with pulmonary hypertension (right-left shunt). There have been few case reports of paradoxical embolism in peripheral arteries coincident with acute pulmonary thromboembolism. Here, we describe a case of paradoxical peripheral embolism associated with PFO complicated by acute pulmonary thromboembolism. The patient had severe peripheral ischemia due to a massive thrombus and was treated successfully by peripheral thrombectomy, thrombolysis, implantation of a permanent inferior vena cava filter and anticoagulation.
Purpose The objective of this study was to determine the mesh contracture, adhesion, tissue ingrowth, and histologic characteristics of a novel absorbable barrier mesh (Ventrio??? ST Hernia Patch) compared to existing permanent (Ventrio??? Hernia Patch) and absorbable barrier meshes (Sepramesh??? IP Composite and PROCEED??? Surgical Mesh). Methods Standard laparoscopic technique was utilized to bilaterally implant meshes in 20 female Yorkshire pigs (n = 5 pigs/group). Meshes were fixated to the intact peritoneum with SorbaFix??? absorbable fixation devices. Mesh contracture, adhesion coverage, and adhesion tenacity were evaluated after 4 weeks. T-Peel testing and hematoxylin and eosin (H&E) staining were utilized to assess tissue ingrowth and host response. Results A significantly great...
The authors report a retrospective study which assesses the results obtained over eight years and the toxicity of an exclusive curietherapy by permanent iodine-125 implants performed at the Nancy centre of struggle against cancer. More than five hundred patients have been treated between December 1999 and December 2007, a first group comprising patients suffering from a low risk cancer and a second group suffering from a medium risk cancer. The authors discuss the survival rates, the existence of side effects, and rectal toxicity results. Short communication
Feasibility study for the investigation of Nitinol self-expanding stents by neutron techniques
In this paper, neutron techniques – in particular, small angle neutron scattering (SANS) and neutron diffraction (ND) – are considered for the non-destructive characterization of Nitinol artery stents. This roughly equiatomic (50Ni–50Tiat%) shape memory alloy (SMA) exhibits significant properties of superelasticity and biocompatibility that make it suitable to be typically used as smart material for medical implants and devices. Nitinol self-expanding artery stents, as permanent vascular support structures, supply an ideal option to bypass surgery, but they are submitted for the whole of patient's life to the dynamical stress of the artery pulsation and the aggression from the biological environment. These stents, consequently, can suffer from wear and fracture occu...
Alternative site pacing: accessing normal precordial activation: is it possible?
Pacemaker implantation is necessary in patients with symptomatic bradycardia. The right ventricular (RV) apex is the traditional pacing site because of its ease of access with simple and reliable technology. However, by forcing mechanical desynchronization, this may induce adverse effects, especially in heart failure patients. To avoid these problems, alternative sites for pacing have been explored with the idea of preserving normal ventricular activation. The His bundle is an obvious target, and results are promising, but permanent pacing is fraught with technical difficulties. Assessment of the RV septum and outflow tract has generated inconclusive results. Significant limitations to trials to date are inconsistency of electrode deployment to selected regions (themselves vaguely defined)...
Recovery of Advanced Atrioventricular Block by Cilostazol
We describe a case of advanced atrioventricular (AV) block, in which treatment with cilostazol was effective in recovering the AV conduction. The patient was referred to our hospital for close examination of the advanced AV block and permanent pacemaker implantation. Although the patient had experienced third-degree AV block with occasional AV synchrony for more than two days, the AV conduction completely recovered after treatment with oral cilostazol at 200 mg/day. Here we discuss the possible mechanism of the improvement in the AV conduction by cilostazol.
Sustained Bundle Branch Reentrant VT. Radiofrequency catheter ablation of the left bundle branch (LBB) was attempted in a patient with sustained bundle branch reentry. During sinus rhythm, the QRS had a complete LBB block pattern, and the LBB was activated retrogradely (transseptal). Ablation of the LBB eliminated inducibility of the tachycardia, while the QRS complex and the duration of the HV interval (70 msec) remained unchanged. Successful ablation of the LBB eliminated bundle branch reentry and yet maintained the anterograde conduction properties of the His-Purkinje system, obviating implantation of a permanent pacemaker. PMID:7743008
Abstract Supernumerary teeth are frequently present in the mixed and permanent dentition and infrequently in the deciduous dentition. Such teeth may cause a delay in normal eruption, crowding and aesthetic problems. Early diagnosis facilitates simpler treatment modalities. Late diagnosis may require the use of more advanced techniques to achieve acceptable aesthetics. This article reports the late presentation of the effects of unilateral maxillary two-tooth anterior hyperdontia and its subsequent surgical management in the mature adult: dental implant replacement therapy and consecutive guided bone regeneration and tissue regeneration therapy were employed in the solution.
The national protocol for paediatric amplification in Australia
Abstract This document describes the national protocol for the selection, fitting, verification, and evaluation of amplification for hearing-impaired children in Australia. It also outlines the approach to management of children who have auditory neuropathy spectrum disorder, children who have mild and unilateral hearing loss, and children who require cochlear implantation. Audiological management of all Australian citizens and permanent residents under twenty-one years of age who have a hearing loss is carried out by the national hearing service provider, Australian Hearing. It is funded by the Australian Government's Hearing Services Program to provide fully subsidised hearing aids, frequency modulated (FM) systems and ongoing audiological management. All hearing aids for children are mu...
Permanent pacemakers are commonly used in veterinary practice and can have a dramatic effect on the treatment of heart block. A Labrador Retriever dog suffering from exercise intolerance secondary to third degree atrioventricular block was treated with a new pacemaker system. A steroid-eluting screw-in type lead that has the advantage of being more fixed to the myocardial wall without increasing the pacing threshold was used. The heart rate was regulated with an acceleration sensing pacemaker generator that included several automatic modulation systems. Nineteen months after implantation, the dog has a normal level of activity. The present case suggests that this pacemaker design may offer important advantages for canine patients.
Endocardial lead-induced tricuspid regurgitation has not been well recognized, either clinically or echocardiographically, and yet it is likely a preventable iatrogenic disease. In severe cases, it can lead to right ventricular failure and require tricuspid valve surgery. This complication will become increasingly important, because the numbers of permanent pacemakers and implantable cardioverter-defibrillators are expected to increase because of the aging population and the expanding capabilities of these devices. Published studies are largely retrospective, and serial studies to assess the time course of the development of tricuspid regurgitation are lacking. The mechanisms and severity of tricuspid regurgitation may not be well evaluated by two-dimensional echocardiography. Real-time th...
Diagnosis of Cardiac Device–Related Infective Endocarditis After Device Removal
Objectives We sought to determine the incidence, diagnostic value, and outcome of intracardiac masses observed by echocardiography after device removal. We hypothesized that these “ghosts” of leads could be associated with the diagnosis of cardiac device–related infective endocarditis (CDRIE). Background The echocardiographic appearance of residual floating masses in the right atrium after removal of permanent pacemakers and implantable cardioverter-defibrillators was recently described. However, the significance of these ghosts and their relationship with CDRIE are unknown. Methods The pre-operative clinical, microbiological, and echocardiographic conditions; the indication; and the removal technique were analyzed in a retrospective cohort including all consecutive pa...
A 67-year-old woman was referred to our hospital with a sudden syncopal attack. She suffered from cardiogenic shock due to left ventricular (LV) outflow stenosis with simultaneous complete atrioventricular (AV) block. An endomyocardial biopsy of the left ventricle demonstrated myocardial disarray and myocardial fibrous and edematous tissue with infiltration of mononuclear cells. Cardiac magnetic resonance imaging (cMRI) detected a damaged septal area that was likely associated with the conduction disturbance. The diagnosis was hypertrophic cardiomyopathy accompanied by acute myocarditis. Although the LV outflow stenosis was transient, the complete AV block was persistent, thus requiring permanent pacemaker implantation.
Permanent or temporary implantation of inferior vena cava filters for protection against pulmonary embolism is well established. There have been numerous devices developed for this purpose, each of which has proprietary design considerations that affect performance and potentially impose limitations with regard to positioning, efficacy and risk profile. This article describes a recently developed, unique inferior vena cava filter design that employs a separated filtration component and a novel double-ring anchoring system that allows intraprocedural capture and repositioning for optimized placement. In addition, early experience suggests easy removal when desired, a high rate of filtration success and excellent caval patency.
Permanent or temporary implantation of inferior vena cava filters for protection against pulmonary embolism is well established. There have been numerous devices developed for this purpose, each of which has proprietary design considerations that affect performance and potentially impose limitations with regard to positioning, efficacy and risk profile. This article describes a recently developed, unique inferior vena cava filter design that employs a separated filtration component and a novel double-ring anchoring system that allows intraprocedural capture and repositioning for optimized placement. In addition, early experience suggests easy removal when desired, a high rate of filtration success and excellent caval patency. PMID:20021237
Concrescence is a rare developmental anomaly with an overall incidence of 0.8% in the permanent dentition. While many case reports describe the treatment of concrescence with extraction, there are few reports of non-surgical root canal treatment (NSRCT), due to the atypical root form, canal morphology, and technical difficulties involved in concrescence. This unique case report describes a technical modification of NSRCT that can retain joined posterior maxillary teeth to maintain natural posterior occlusion without surgical intervention or dental implants, thereby avoiding the risk of damage to a large portion of the alveolar bone near the maxillary sinus. (J Oral Sci 54, 133-136, 2012)
Engineering Endochondral Bone: In Vivo Studies
The use of biomaterials to replace lost bone has been a common practice for decades. More recently, the demands for bone repair and regeneration have pushed research into the use of cultured cells and growth factors in association with these materials. Here we report a novel approach to engineer new bone using a transient cartilage scaffold to induce endochondral ossification. Chondrocyte/chitosan scaffolds (both a transient cartilage scaffold?experimental?and a permanent cartilage scaffold?control) were prepared and implanted subcutaneously in nude mice. Bone formation was evaluated over a period of 5 months. Mineralization was assessed by Faxitron, micro computed tomography, backscatter electrons, and Fourier transform infrared spectroscopy analyses. Histological analysis provided furthe...
Background Children requiring permanent pacing have a lifelong need for follow-up. Epicardial leads have traditionally fared worse than endocardial counterparts. We tested the hypothesis that steroid-eluting epicardial and endocardial leads had equivalent outcomes. Methods We reviewed medical records of 148 children, mean age 8.2 ± 4.8 years, in whom a dual-chamber pacemaker system with steroid-eluting leads from a single manufacturer was implanted. Primary outcome was mortality. Secondary outcomes included freedom from lead failure and pacemaker system reintervention. Loss of capture-sensing, lead displacement-fracture, exit block, and high thresholds constituted lead failure. Reintervention included need for lead revision or generator change. Results There was no early mortality. ...
Abstract Both temporary and permanent orthopedic implants have, by default or design, surface chemistry, and topography. There is increasing evidence that controlling nanodisorder can result in increased osteogenesis. Block co-polymer phase separation can be used to fabricate a nanotopography exhibiting a controlled level of disorder, both reproducibly and cost-effectively. Two different topographies, produced through the use of block co-polymer phase separation, were embossed onto the biodegradable thermoplastic, polycaprolactone (PCL). Analysis of the topography itself was undertaken with atomic force microscopy, and the topography's effect on human osteoblasts studied through the use of immunocytochemistry and fluorescence microscopy. Planar controls had a surface roughness 0.93-nm, and...
Transcatheter aortic valve implantation with a self-expanding nitinol bioprosthesis
Abstract Objective: To ascertain incidence and predictors of new permanent pacemaker (PPM) following transcatheter aortic valve implantation (TAVI) with the self-expanding aortic bioprosthesis. Background: TAVI with the Medtronic Corevalve (MCV) Revalving System (Medtronic, Minneapolis, MN) has been associated with important post-procedural conduction abnormalities and frequent need for PPM. Methods: Overall, 73 consecutive patients with severe symptomatic AS underwent TAVI with the MCV at two institutions; 10 patients with previous pacemaker and 3 patients with previous aortic valve replacement were excluded for this analysis. Clinical, echocardiographic, and procedural data were collected prospectively in a dedicated database. A standard 12-lead ECG was recorded in all patients at baseli...
Permanent Pacemaker-Induced Superior Vena Cava Syndrome: Successful Treatment by Endovascular Stent
The use of metallic stents in the management of benign and malignant superior vena cava syndrome (SVCS) is well documented. Symptomatic stenosis or occlusion of the SVC is a rare complication of a transvenous permanent pacemaker implant. Suggested treatments have included anticoagulation therapy, thrombolysis, balloon angioplasty and surgery. More recently, endovascular stenting has evolved as an attractive alternative but the data available in the literature are limited. We describe a case in which venous stenting with a Wallstent endoprosthesis was used successfully. The patient remains symptom free and with normal pacemaker function 36 months later.
Imaging the islet graft by positron emission tomography
Clinical islet transplantation is being investigated as a permanent cure for type 1 diabetes mellitus (T1DM). Currently, intraportal infusion of islets is the favoured procedure, but several novel implantation sites have been suggested. Noninvasive longitudinal methodologies are an increasingly important tool for assessing the fate of transplanted islets, their mass, function and early signs of rejection. This article reviews the approaches available for islet graft imaging by positron emission tomography and progress in the field, as well as future challenges and opportunities.
Subtypes of neuronal nicotinic acetylcholine receptors (nAChRs) are differentially sensitive to up-regulation by chronic nicotine exposure in vitro. To determine whether this occurs in animals, rats were implanted with minipumps containing saline +/- nicotine (6.0 mg/kg/rat/day) for 14 days. Autoradiography with [125I]epibatidine using 3-(2(S)-azetidinylmethoxy)pyridine dihydrochloride (A-85380) or cytisine as selective competitors allowed quantitative measurement in 33 regions of 3 families of nAChR binding, with properties of alpha4beta2, alpha3beta4, and alpha3/alpha6beta2. Chronic nicotine exposure caused increases of 20 to 100% for alpha4beta2-like binding in most regions surveyed. However, binding to this subtype was not increased in some regions, including habenulopeduncular structures, certain thalamic nuclei, and several brainstem regions. In 9 of 33 regions, including catecholaminergic areas and visual structures, alpha3/alpha6beta2-like binding represented >10% of total binding. Binding to this subtype was up-regulated by nicotine in only two of these nine regions: the nucleus accumbens and superior colliculus. alpha3beta4-Like binding represented >10% of total in 15 of the 33 regions surveyed. Binding to this subtype was increased by nicotine in only 1 of these 15 regions, and actually decreased in subiculum and cerebellum. These studies yielded two principal findings. First, chronic nicotine exposure selectively up-regulates alpha4beta2-like binding, with relatively little effect on alpha3/alpha6beta2-like and alpha3beta4-like binding in vivo. Second, up-regulation by chronic nicotine exposure shows considerable regional variation. Differential subtype sensitivity to chronic nicotine exposure may contribute to altered pharmacological response in individuals who smoke or use nicotine replacement therapy. PMID:14560040
Treatment of Hammertoe Deformity Using a One-piece Intramedullary Device: A Case Series
Hammertoes are common deformities that are often surgically treated using arthrodesis or arthroplasty of the proximal interphalangeal joint with percutaneous, temporary Kirschner wire fixation. However, percutaneous Kirschner wire fixation is associated with potential complications, including wire migration, breakage, and pin tract infection. Furthermore, the complications of pseudoarthrosis and nonunion are seen using this technique owing to a lack of rotational control of the Kirschner wire. Another drawback of this implant is the need for wire removal and the associated patient anxiety with this in-office procedure. In the present series of 7 toes in 3 patients, we describe an alternative method of hammertoe fixation using a permanently implanted, 1-piece intramedullary device used to s...
Welding methods for joining thermoplastic polymers for the hermetic enclosure of medical devices
New high performance polymers have been developed that challenge traditional encapsulation materials for permanent active medical implants. The gold standard for hermetic encapsulation for implants is a titanium enclosure which is sealed using laser welding. Polymers may be an alternative encapsulation material. Although many polymers are biocompatible, and permeability of polymers may be reduced to acceptable levels, the ability to create a hermetic join with an extended life remains the barrier to widespread acceptance of polymers for this application. This article provides an overview of the current techniques used for direct bonding of polymers, with a focus on thermoplastics. Thermal bonding methods are feasible, but some take too long and/or require two stage processing. Some methods...
Welding methods for joining thermoplastic polymers for the hermetic enclosure of medical devices.
New high performance polymers have been developed that challenge traditional encapsulation materials for permanent active medical implants. The gold standard for hermetic encapsulation for implants is a titanium enclosure which is sealed using laser welding. Polymers may be an alternative encapsulation material. Although many polymers are biocompatible, and permeability of polymers may be reduced to acceptable levels, the ability to create a hermetic join with an extended life remains the barrier to widespread acceptance of polymers for this application. This article provides an overview of the current techniques used for direct bonding of polymers, with a focus on thermoplastics. Thermal bonding methods are feasible, but some take too long and/or require two stage processing. Some methods are not suitable because of excessive heat load which may be delivered to sensitive components within the capsule. Laser welding is presented as the method of choice; however the establishment of suitable laser process parameters will require significant research. PMID:20570545
An N-of-1 Trial as an Aid to Decision-Making Prior to Implanting a Permanent Spinal Cord Stimulator
ABSTRACT Objective. Limited evidence supports the efficacy of spinal cord stimulation (SCS). Therefore, it is crucial to assess the usefulness of this invasive procedure before implanting permanent electrodes in each patient. An N-of-1 trial is an experiment in which a single participant undergoes periods of comparative treatments. We illustrate how an N-of-1 trial design may permit clinicians to conduct such an assessment in an individual patient. Design. Case report. Setting. University teaching hospital. Patients. A 61-year-old man patient with refractory postherpetic neuralgia scheduled for SCS implantation. Interventions. Percutaneous octapolar lead placement into the epidural space for SCS at T5-T6, and placement of transcutaneous electrical nerve stimulator (TENS) electrodes upon th...
Surgeons are commonly confronted with breast contour deformities and defects that result from previous surgical interventions. These soft tissue deformities can be corrected by conventional reconstructive flap surgery using autologous tissue, but there can be donor site morbidity. Smaller volume replacement is possible using temporary fillers such as hyaluronic acid or polylactic acid, or by using 'permanent' fillers such as autologous fat, but large defects are notoriously difficult to fill and often the fillers resorb or migrate. The patient described in this case report had an exchange of polyurethane implant (PU) in the left breast and correction of a contralateral breast contour filling deformity. A left breast partial capsulectomy was performed after implant removal and the capsule g...
Subcutaneous electrocardiogram monitors and their field of view
Continuous electrocardiogram (ECG) monitoring of cardiac patients on a long-term, even permanent, basis has become possible. Postsurgical cases, those with significant risk factors, or patients with chronic conditions are candidates for these procedures to assess evolving risk factors and detect life-threatening events. A small sensing device can be implanted subcutaneously to assess the ECG, transmitting status and alerts to local caregivers or a remote monitoring service. We and others have shown that a differential electrode pair with only 2- to 3-cm spacing can produce QRS amplitudes greater than 1 mV, sufficient to accurately identify asystole, tachyarrhythmias, and ST-segment changes. Medtronic's REVEAL and St Jude Medical's CONFIRM are implantable look recorders (ILRs) with a single...
Clinical Cardiac Pacing and Defibrillation. Current Opinion in Pathology.
Normal rhythms originate in the sino-atrial node, a specialized cardiac tissue consisting of only a few thousands of pacemaker cells. Malfunction of pacemaker cells due to diseases or aging leads to rhythm generation disorders (for example, bradycardias and sick-sinus syndrome (SSS)), which often necessitate the implantation of electronic pacemakers. Although effective, electronic devices are associated with such shortcomings as limited battery life, permanent implantation of leads, lead dislodging, the lack of autonomic responses and so on. Here, various gene- and cell-based approaches, with a particular emphasis placed on the use of pluripotent stem cells and the hyperpolarization-activated cyclic nucleotide-gated-encoded pacemaker gene family, that have been pursued in the past decade to reconstruct bio-artificial pacemakers as alternatives will be discussed in relation to the basic biological insights and translational regenerative potential. PMID:15825873
Antioxidant and osteogenic properties of anodically oxidized titanium
Cells adhering onto implant surfaces are subjected to oxidative stress during wound healing processes. Although titanium and its alloys are among the most frequently used biomaterials in orthopedic and dental implants, titanium surfaces do not have antioxidant properties, and cells grown on these surfaces can show permanent oxidative stress. The present study assessed the antioxidant property and osteogenic properties of titanium samples with or without oxidation treatments. A thick rutile TiO"2 film was observed on thermally oxidized titanium surfaces, while amorphous anatase TiO"2 formed on anodically oxidized titanium surfaces prepared by discharging in 1 M Na"2HPO"4. A resistance to the depletion of reduced glutathione in adherent osteoblasts, which correlates with antioxidant behavior...
Objective To evaluate the accuracy, utility, and cost effectiveness of a new electromagnetic patient positioning and continuous, real-time monitoring system, which uses permanently implanted resonant transponders in the target (Calypso® 4D Localization System and Beacon® transponders, Seattle, WA) to continuously monitor tumor location and movement during external beam radiation therapy of the prostate. Materials and methods This clinical trial studied 43 patients at 5 sites. All patients were implanted with 3 transponders each. In 41 patients, the system was used for initial alignment at each therapy session. Thirty-five patients had continuous monitoring during their radiation treatment. Over 1,000 alignment comparisons were made to a commercially available kV X-ray positio...
Neuromodulation sacree avec le systeme InterStim(TM) : resultats du registre national francais
Aim: To analyse current practice patterns and to evaluate (long-term) effectiveness and adverse events of sacral neuromodulation with InterStim(TM) Therapy based on data collected in a national register and to discuss the strengths and weaknesses of the register. Patients and methods: This is a French multicenter prospective observational trial including patients with a permanent implant (2003-2009). Voiding diary variables and patient satisfaction were analysed based on last follow-up visit since implantation. Results: One thousand four hundred and eighteen patients (median age: 63 years, 1206 females) were included in the database (median follow-up: 12 months). One thousand and eighty-nine patients had non-neurological disease. The principal diagnosis was overactive bladder syndrome ([OA...
Summary INTRODUCTION: The aim of this retrospective study was to evaluate late toxicity and biochemical disease-free survival of patients with primary localised prostate cancer, who had been treated with permanent seed implantation at the radiotherapy department of the Medical University of Vienna. METHODS AND MATERIALS: Between 08/1999 and 11/2006 100 patients were treated with ultrasound guided transperineal seed implantation (94 patients with Iodine and 6 patients with Palladium). 53 patients received additional hormone therapy. According to T-stage, Gleason Score and PSA, patients were divided into three risk groups (low, intermediate and high risk). Late gastrointestinal and genitourinary side effects and biochemical disease-free survival were evaluated. RESULTS: The patients were fol...
[Musculoskeletal infections in the era of multiresistant pathogens].
The burden of musculoskeletal infections is permanently growing. A probable explanation for this development could be the increasing number of elderly people undergoing extensive surgery using implants and prosthetic devices while having more significant comorbidities (e.g. cardiovascular, metabolic and malignant). However, a relative reduction of acute (hematogenous) osteomyelitis compared to the occurrence of much more complex situations, such as diabetic foot syndrome or chronic osteitis and prosthetic implant infections is being observed. This poses new challenges for the clinician in managing these patients. Furthermore, there is the evolving threat of antimicrobial resistance as well as the increasing amount of infections with Gram-negative pathogens. Several aspects have to be considered for successful management of musculoskeletal infections: the site of infection and feasibility of local surgical treatment, the effectiveness of antimicrobial treatment, the inclusion of comorbidities and their specific treatment in an advanced therapeutic concept as well as the interdisciplinary approach led by surgeons and infectious disease specialists. PMID:22639059
Improved Procedural Results After CoreValve Implantation with the New AccuTrak Delivery System
Aims of the study: Transcatheter aortic valve implantation (TAVI) has become an established treatment for severe aortic stenosis in patients with unacceptable high-surgical risk. Recently, the new AccuTrak delivery system for improved deliverability of the CoreValve aortic bioprosthesis was launched. It has not yet been shown if the new delivery catheter leads to optimized positioning and improved procedural outcomes. Methods and results: We conducted a retrospective single-center analysis and evaluated 70 consecutive patients (35 with the original delivery catheter and 35 with the new AccuTrak catheter) for anatomic positioning and related outcome parameters like postinterventional aortic regurgitation (AR) and the need for permanent pacemaker insertion, after CoreValve implantation. The ...
BackgroundDecompensated heart failure (HF) is associated with unacceptable morbidity and mortality risks. Recent implantable technology advancements allow frequent filling pressure monitoring and provide insight into HF pathophysiology and a new tool for HF management. MethodsThe CHAMPION trial is a prospective, multicenter, randomized, single-blind clinical trial testing the hypothesis that HF management guided by frequently assessed pulmonary artery pressures is superior to traditional methods. A total of 550 subjects with New York Heart Association (NYHA) functional class III HF were enrolled at 64 sites in the United States. All subjects received the CardioMEMS HF sensor as a permanent pulmonary artery implant and were randomized to the treatment or the control group before discharge. ...
Carga inmediata en implantes dentales Implantología
Abstract in spanish El avance tecnológico con respaldo científico de los últimos cuarenta años ha ubicado a la Implantodoncia dentro de la Odontología, no sólo como una filosofía de trabajo sino más bien como una verdad científica comprobada. La vigencia de la Osteointegraciòn propuesta en la década de los ochenta ha obligado a seguir investigando en la histología de la interfaz ósea de los implantes dentales como una base de sustentación científica permanente. Abstract in english The technological advance with scientific support of last forty years, has located the Implantodonthics whitin dentistry, not only as a working philosophy, but rather as a scientific verified truth. The validity of the osseous integration proposed in the decade of the eighties has forced further research in the bone histology of the interface of dental implants as a base of permanent scientific support.
Abstract in spanish Objetivos: Analizar la variación de parámetros relativos al electrodo de fijación activa en el implante y seguimiento posterior durante 6 meses de fase aguda de implante. Diseño: Estudio descriptivo, analítico, prospectivo, observacional sobre cohorte de casos sucesivos durante 8 meses (abril-diciembre de 2010). Ámbito: Unidad de electro-estimulación cardiaca de un Servicio de Medicina Intensiva. Pacientes o participantes: Pacientes sometidos a implante de marcapas (more) os definitivo con electrodos de fijación activa, implantados en aurícula y ventrículo, Intervenciones: medición de variables descritas con analizador de umbrales durante la fijación de electrodo y en los diferentes momentos del estudio, Variables principales que se comparan; umbral, impedancia y actividad intrínseca tanto auricular como ventricular antes y después de la fijación del electrodo, a las 48h, al mes y 6 meses de seguimiento, Se realizaron comparaciones utilizando test T-student para datos pareados; con significación si p Abstract in english Objectives: To analyze the variations in the parameters relative to active fixation electrodes at the time of implantation and over subsequent follow-up during 6 months of the acute phase of implantation. Design: A descriptive, analytical, prospective, observational cohort study was made of consecutive cases over a period of 8 months (April-December 2010). Setting: Pacing unit of an Intensive Care Unit. Patients or participants: Patients undergoing permanent pacemaker imp (more) lantation with active fixation electrodes, implanted in both atrium and ventricle, Interventions: Measurement of variables described with a threshold analyzer during electrode fixation and at different times during the study, Main compared variables: threshold, impedance and intrinsic activity (both atrial and ventricular) before and after fixation, at 48hours, at one month and 6 months, Comparisons were made using the Student t-test for paired data, assuming significance for p
Results of brachytherapy for cancer of the tongue with special emphasis on local prognosis
One hundred and sixty-six patients with squamous cell carcinoma of the tongue were treated with radiation. Treatment modalities were mainly interstitial implant with or without external beam irradiation, except for early lesions, which were treated with intraoral electron beam therapy. Analysis was made on the local prognosis of the lesion to clarify the indications for interstitial therapy, especially the combined program with external beam therapy, and the time-dose relationship of the brachytherapy. Local recurrence-free rates (two years) were 94% in T1, 77% in T2 and 32% in T3 lesions, respectively. For T1 and surperficial or exophytic T2 lesions, the local recurrence-free rate was excellent with the interstitial therapy alone using either permanent implants of gold grain or radium implants. Therefore, prior external beam therapy seemed to be unnecessary for these lesions. When the treated area was less than 10 cm/sup 2/, subsequent complications were not likely even if the TDF (time-dose factor) value was high. Most of the patients who received combined external beam and interstitial therapy showed infiltrative T2 and a majority of the T3 lesions. In these patients, it was apparent that most of the total dose should be given from the interstitial implant after a small prior dose with external irradiation, because these lesions could not be cured even if the external dose was increased.
UroLift system for relief of prostate obstruction under local anesthesia.
Many men with benign prostatic hyperplasia (BPH) forego therapy because they are dissatisfied with current treatment options. While surgical resection and ablation using many different forms of energy remain the reference standard for BPH treatment, many men seek a less invasive technique that will improve symptoms but not risk the complications associated with tissue removal. The Prostatic Urethral Lift opens the prostatic urethra with UroLift (NeoTract Inc., Pleasanton, CA, USA) permanent implants that are delivered under cystoscopic visualization. The implants literally "hold open" the lateral prostatic lobes creating a passage through the obstructed prostatic urethra. Voiding and symptoms are significantly improved without the morbidity or possible complications following prostate resection. The entire procedure can be readily performed using local anesthesia. As with all new implant procedures, the technique has evolved with experience. The objective of this article is to describe the most current technique for the delivery of the UroLift implant in order to achieve maximal impact on symptom relief. PMID:22512970
Transgenic BDNF induces nerve fiber regrowth into the auditory epithelium in deaf cochleae.
Sensory organs typically use receptor cells and afferent neurons to transduce environmental signals and transmit them to the CNS. When sensory cells are lost, nerves often regress from the sensory area. Therapeutic and regenerative approaches would benefit from the presence of nerve fibers in the tissue. In the hearing system, retraction of afferent innervation may accompany the degeneration of auditory hair cells that is associated with permanent hearing loss. The only therapy currently available for cases with severe or complete loss of hair cells is the cochlear implant auditory prosthesis. To enhance the therapeutic benefits of a cochlear implant, it is necessary to attract nerve fibers back into the cochlear epithelium. Here we show that forced expression of the neurotrophin gene BDNF in epithelial or mesothelial cells that remain in the deaf ear induces robust regrowth of nerve fibers towards the cells that secrete the neurotrophin, and results in re-innervation of the sensory area. The process of neurotrophin-induced neuronal regeneration is accompanied by significant preservation of the spiral ganglion cells. The ability to regrow nerve fibers into the basilar membrane area and protect the auditory nerve will enhance performance of cochlear implants and augment future cell replacement therapies such as stem cell implantation or induced transdifferentiation. This model also provides a general experimental stage for drawing nerve fibers into a tissue devoid of neurons, and studying the interaction between the nerve fibers and the tissue. PMID:20109446
Titanium and cobalt alloys, as well as some stainless steels, are among the most frequently used materials in orthopaedic surgery. In industrialized countries, stainless steel devices are used only for temporary implants due to their lower corrosion resistance in physiologic media when compared to other alloys. However, due to economical reasons, the use of stainless steel alloys for permanent implants is very common in developing countries. The implantation of foreign bodies is sometimes necessary in the modern medical practice. However, the complex interactions between the host and the can implant weaken the local immune system, increasing the risk of infections. Therefore, it is necessary to further study these materials as well as the characteristics of the superficial film formed in physiologic media in infection conditions in order to control their potential toxicity due to the release of metallic ions in the human body. This work presents a study of the superficial composition and the corrosion resistance of AISI 316L stainless steel and the influence of its main alloying elements when they are exposed to an acidic solution that simulates the change of pH that occurs when an infection develops. Aerated simulated body fluid (SBF) was employed as working solution at 37 degrees C. The pH was adjusted to 7.25 and 4 in order to reproduce normal body and disease state respectively. Corrosion resistance was measured by means of electrochemical impedance spectroscopy (EIS) and anodic polarization curves. PMID:17999036
["Molar-incisor hypomineralization"].
Hypocalcification of the enamel is the most common developmental disorder observed in teeth. The prevalence of this kind of hypomineralisation is about 10-19%. These molars are often referred to as cheese molars, because the lesions clinically resemble cheese in color and consistency. Other descriptions are: idiopathic enamel hypomineralisation in the permanent first molars, idiopathic enamel opacities in the permanent first molars, non fluoride enamel hypomineralisation in the permanent first molars, non-endemic mottling of enamel in the permanent first molars. Molar-Incisor Hypomineralisation is today the proposed expression for this disease. Occlusal surfaces of the first permanent molar are most commonly affected. The lesions are more frequent in the upper jaw than in the lower jaw. The incisors are affected to a lesser degree than the molars. Several aetiological factors can cause these defects. Some studies show a relation between intake of dioxins via mother's milk after prolonged breast feeding and developmental defects of the child's teeth. Because the ameloblasts are very sensitive to oxygen supply, complications involving oxygen shortages during birth or respiratory diseases such as asthma or bronchitis and pneumonia are discussed as further aetiological factors. Renal insufficiency, hypoparothyroidism, diarrhoea, malabsorption and malnutrition and high-fever diseases can be other reasons for the occurrence of these defects. Defective enamel can be a locus of lowered resistance for caries. Histologically there are areas of porosity of varying degrees. The affected teeth can be very sensitive to air, cold, warm and mechanical stimuli. Toothbrushing may create toothache in these teeth. We therefore suggest that these patients receive intensified prevention with fluoride varnish, a fissure sealing, GIZ, composits, stainless steel crowns or implants. In some cases an interdisciplinary approach with an orthodontist can result in the extraction of the molars in the age of 8 to 10 years. PMID:15106501
[(125)I]EYF: a new high affinity radioligand to neuropeptide FF receptors.
[(125)I]EYF ([(125)I]EYWSLAAPQRFamide), a new radioiodinated probe derived from a peptide present in the rat Neuropeptide FF precursor (EFWSLAAPQRFamide, EFW-NPSF) was synthesized and its binding characteristics investigated on sections of the rat spinal cord and on membranes of mouse olfactory bulb. In both tissues, [(125)I]EYF binding was saturable and revealed a very high affinity interaction with a single class of binding sites in rat and mouse (K(D) = 0.041 and 0.019 nM, respectively). Competition studies showed that [(125)I]EYF bound to one class of binding sites exhibiting a high affinity for all the different peptides the precursor could generate (NPA-NPFF, SPA-NPFF, NPFF, EFW-NPSF, QFW-NPSF) with the exception of NPSF which displayed a low affinity. Autoradiographic studies demonstrated that [(125)I]EYF binding sites were fully inhibited by a synthetic Neuropeptide FF agonist (1DMe) in all areas of the rat brain. The density of [(125)I]EYF binding sites was high in the intralaminar thalamic nuclei, the parafascicular thalamic nucleus and in the superficial layers of the dorsal horn. Non specific binding reached 5-10% of the total binding in all brain areas. Similarly, in mouse brain experiments, the non-specific binding was never superior to 10%. These findings demonstrate that putative neuropeptides generated by the Neuropeptide FF precursor and containing the NPFF or NPSF sequences should bind to the same receptor. Furthermore, these data indicate that [(125)I]EYF is a useful radiolabeled probe to investigate the NPFF receptors; its major advantages being its high affinity and the very low non-specific binding it induces. PMID:11311733
The 5-HT2 (serotonin) receptor has traditionally been labeled with antagonist radioligands such as (3H)ketanserin and (3H)spiperone, which label both agonist high-affinity (guanyl nucleotide-sensitive) and agonist low-affinity (guanyl nucleotide-insensitive) states of this receptor. The hallucinogen 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) is an agonist which labels the high-affinity guanyl nucleotide-sensitive state of brain 5-HT2 receptors selectively. In the present study, conditions for autoradiographic visualization of (+/-)-(125I)DOI-labeled 5-HT2 receptors were optimized and binding to slide-mounted sections was characterized with respect to pharmacology, guanyl nucleotide sensitivity and anatomical distribution. In slide-mounted rat brain sections (+/-)-(125I)DOI binding was saturable, of high affinity (KD approximately 4 nM) and displayed a pharmacologic profile typical of 5-HT2 receptors. Consistent with coupling of 5-HT2 receptors in the high-affinity state to a guanyl nucleotide regulatory protein, (125I)DOI binding was inhibited by guanyl nucleotides but not by adenosine triphosphate. Patterns of autoradiographic distribution of (125I)DOI binding to 5-HT2 receptors were similar to those seen with (3H)ketanserin- and (125I)-lysergic acid diethylamide-labeled 5-HT2 receptors. However, the density of 5-HT2 receptors labeled by the agonist (125I)DOI was markedly lower (30-50%) than that labeled by the antagonist (3H)ketanserin. High densities of (125I)DOI labeling were present in olfactory bulb, anterior regions of cerebral cortex (layer IV), claustrum, caudate putamen, globus pallidus, ventral pallidum, islands of Calleja, mammillary nuclei and inferior olive. Binding in hippocampus, thalamus and hypothalamus was generally sparse.
The effects of pertussis toxin treatment on the characteristics of somatostatin receptors in the anterior pituitary tumor cell line AtT-20 were examined. Pertussis toxin selectively catalyzed the ADP ribosylation of the alpha subunits of the inhibitory GTP binding proteins in AtT-20 cells. Toxin treatment abolished somatostatin inhibition of forskolin-stimulated adenylyl cyclase activity and somatostatin stimulation of GTPase activity. To examine the effects of pertussis toxin treatment on the characteristics of the somatostatin receptor, the receptor was labeled by the somatostatin analog (125I)CGP 23996. (125I)CGP 23996 binding to AtT-20 cell membranes was saturable and within a limited concentration range was to a single high affinity site. Pertussis toxin treatment reduced the apparent density of the high affinity (125I)CGP 23996 binding sites in AtT-20 cell membranes. Inhibition of (125I)CGP 23996 binding by a wide concentration range of CGP 23996 revealed the presence of two binding sites. GTP predominantly reduced the level of high affinity sites in control membranes. Pertussis toxin treatment also diminished the amount of high affinity sites. GTP did not affect (125I)CGP 23996 binding in the pertussis toxin-treated membranes. The high affinity somatostatin receptors were covalently labeled with (125I) CGP 23996 and the photoactivated crosslinking agent n-hydroxysuccinimidyl-4-azidobenzoate. No high affinity somatostatin receptors, covalently bound to (125I)CGP 23996, were detected in the pertussis toxin-treated membranes. These results are most consistent with pertussis toxin uncoupling the inhibitory G proteins from the somatostatin receptor thereby converting the receptor from a mixed population of high and low affinity sites to only low affinity receptors.
Studies were undertaken to determine whether deoxyribonuclease I, (DNase I) once immobilized on activated nylon microspheres, would be capable of degrading circulating DNA in vitro and in vivo in an extracorporeal circulation system in dogs. Nylon microspheres were prepared and after gentle hydrolysis and glutaraldehyde treatment, demonstrated a retention of up to 4.73 mg of Dnase I. In vitro studies showed that DNase I immobilized on microspheres degreded a significant percentage of 125I-native DNA (nDNA) within 15 min. Mongrel dogs were injected with 125I-nDNA and a variation in initial t 1/2 in individual animals was observed. Therefore, for experimental studies, 125I-nDNA was injected and decay was recorded during a control period in which untreated microcapsules were utilized in the extracorporeal system. DNase I microspheres were then introduced into the extracorporeal circuit which resulted in an acceleration of degradation of acid precipitable 125I-nDNA. When 200 mug of unlabeled DNA with 125I-nDNA was injected, a similar augmentation of DNA degradation was noted after extracorporeal circulation over DNase I microcapsules. This effect could not be attributed to release of DNase I from the microspheres since no 131I-DNase was detected in the serum or organs of the dogs at the conclusion of the experiments. 125I-nDNA:anti-DNA complexes were passively injected into dogs and after a similar control period of circulation over untreated microcapsules. DNase I microspheres were introduced. Results showed a rapid acceleration in the degradation rate of 125I-nDNA:anti-DNA complexes precipitable with (NH4)2SO4. Extracorporeal circulation over nylon microspheres resulted in no significant alteration of the host's hematocrit or platelet count, and little residual cellular debris on the microcapsules. These data suggest that DNAase immobilized on nylon microspheres may have a potential role in the specific therapy of systemic lupus erythematosus, when it is desirable to hydrolyze DNA circulating free or in combination with antibody. PMID:1262466
Neuronal bungarotoxin (NBT), a snake venom neurotoxin, selectively blocks nicotinic receptors in many peripheral and central neuronal preparations. alpha-Bungarotoxin (alpha BT), on the other hand, a second toxin isolated from the venom of the same snake, is an ineffective nicotinic antagonist in most vertebrate neuronal preparations studied thus far. To examine central nicotinic receptors recognized by NBT, we have characterized the binding of 125I-labeled NBT (125I-NBT) to rat brain membranes and have mapped the distribution of 125I-NBT binding in brain sections using quantitative light microscopic autoradiography. The binding of 125I-NBT was found to be saturable, of high affinity, and heterogeneously distributed in the brain. Pharmacological studies suggested that more than one population of sites is labeled by 125I-NBT. For example, one component of 125I-NBT binding was also recognized by alpha BT, while a second component, not recognized by alpha BT, was recognized by the nicotinic agonist nicotine. The highest densities of these alpha BT-insensitive, nicotine-sensitive sites were found in the fasciculus retroflexus, the lateral geniculate nucleus, the medial terminal nucleus of the accessory optic tract, and the olivary pretectal nucleus. alpha BT-sensitive NBT binding sites were found in highest density in the lateral geniculate nucleus, the subthalamic nucleus, the dorsal tegmental nucleus, and the medial mammillary nucleus (lateral part). The number of brain regions with a high density of 125I-NBT binding sites, blocked either by alpha BT or by nicotine, is low when compared with results obtained using other approaches to studying the central distribution of nicotinic receptors, such as labeling with 3H-nicotine or labeling with cDNA probes to mRNAs coding for putative receptor subunits.
Effects of bile salts on the radioimmunoassay of hormonal peptides
The effect of bile salts on RIAs of secretin, glucagon, insulin, and gastrin have been studied. Increasing concentrations of the sodium salts of taurocholic, glycochenodeoxycholic, taurochenodeoxycholic, glycocholic, and taurodeoxycholic acids progressively inhibit the binding of /sup 125/I-secretin to specific antibody, resulting in significant lowering of the B/F ratio at concentrations as low as 0.04 mM and almost complete inhibition at concentrations above 2.4 mM. The nonspecific inhibition by taurodeoxycholate results in a B/F vs concentration curve resembling a secretin standard curve.The binding of /sup 125/I-secretin to charcoal is also inhibited by increasing concentrations of bile salts, although this effect is less marked than their effects on the immune reaction. The binding of /sup 125/I-glucagon, /sup 125/I-insulin, and /sup 125/I-gastrin to specific antisera is also inhibited by sodium taurocholate. Insulin binding is least affected. However, gastrin binding is inhibited by sodium taurocholate at a concentration as low as 0.2 mM. The binding of /sup 125/I-insulin and /sup 125/I-gastrin to charcoal is also inhibited by sodium taurocholate. Thus bile salts interfere in the RIA of hormonal peptides by inhibiting both the immune reaction and the binding of labeled antigen to charcoal. These nonspecific effects must therefore be considered in RIA of body fluids containing high concentrations of bile salts. Treatment of plasma samples with anionic-binding resins can eliminate interference caused by high bile salt concentrations. However, these resins will also remove anionic hormonal peptides such as gastrin.
The intracellular distribution of /sup 125/I-labeled nerve growth factor (NGF) in rat pheochromocytoma PC12 cells was studied by quantitative electron microscopic (EM) autoradiography and by subcellular fractionation. PC12 cells were grown as monolayer cultures in medium supplemented with serum in the presence of /sup 125/I-NGF. EM autoradiography showed that /sup 125/I-NGF was localized at the plasma membrane and cytoplasmic compartments but did not accumulate in the nuclear chromatin or in the nuclear membrane compartment of cells analyzed after 1 hr and 1, 2, and 8 d of incubation with /sup 125/I-NGF. /sup 125/I-NGF also was not detected in nuclear subcellular fractions prepared from cells grown in serum-supplemented medium either in suspension for 1 d or in monolayer cultures for 1 to 8 d. In contrast, and in confirmation of the results of Yankner and Shooter, about 60% of the cell-bound /sup 125/I-NGF was found in the nuclear pellet after cell fractionation if the cells had been kept previously in suspension for 1 d in phosphate-buffered saline supplemented with 0.2% glucose, 0.1% bovine serum albumin, and /sup 125/I-NGF. The ultrastructure of PC12 cells grown under such conditions, however, revealed signs of varying degrees of damage. Autoradiography of the nuclear pellet from these cells showed the grains to be located mainly over damaged nuclei or over cell debris between nuclei. It is concluded that NGF, after binding to specific receptors at the plasma membrane, is transferred to membrane-confined cytoplasmic compartments but does not have to be transferred further to the nuclear membrane or to the nuclear chromatin as a prerequisite for its physiological action.
Identification and characterization of cellular receptors for the growth regulator, oncostatin M
Oncostatin M is a polypeptide growth regulator produced by activated T cells and phorbol ester-treated U937 cells. To identify specific cellular receptors for this factor, we have characterized the binding of 125I-labeled oncostatin M to a variety of normal and malignant mammalian cells. Recombinant oncostatin M was labeled with 125I with full retention of growth inhibitory activity on A375 melanoma cells. 125I-Oncostatin M bound to sensitive cells in a time- and temperature-dependent fashion. Binding was specifically inhibited by unlabeled native or recombinant oncostatin M, but not by other polypeptide growth factors tested. Binding to human leukemic and normal blood cells was generally less than to nonhematopoietic cells. With four different cell lines, maximal growth inhibition by oncostatin M was achieved at less than maximal binding site occupancy. Scatchard graphs of direct binding data were curvilinear and indicated that 125I-oncostatin M bound with higher apparent affinity at lower 125I-oncostatin M concentrations. Using a two binding site model, affinity constants of Kd1 = 11 +/- 11 pM and Kd2 = 1000 +/- 380 pM were extrapolated from binding data with A375 cells, and values of Kd1 = 3 +/- 2 pM and Kd2 = 400 +/- 44 pM from A549 cells. The major 125I-oncostatin M binding species in a number of mammalian cell lines was identified by chemical cross-linking as a specific protein(s) of Mr = 150,000-160,000. 125I-Oncostatin M was internalized (t1/2 = 30 min) and degraded subsequent to binding to a responsive cell line.
Specific binding of /sup 125/I-human epidermal growth factor (hEGF) to homogenates of term human placentas and fetal membranes from normal and appropriate for gestational age (N = 20), intrauterine growth retarded (N = 9), twin (N = 11), White class AB diabetic (N = 12), and large for gestational age (N = 13) pregnancies was measured. In all pregnancy states, placentas bound approximately four times more /sup 125/I-hEGF than did fetal membranes (P<0.0001). There was no significant differnce in /sup 125/I-hEGF binding to fetal membranes from the various pregnancy states (P<0.05). /sup 125/I-hEGF specific binding to placentas from intrauterine growth retarded or twin pregnancies was significantly greater compared with placentas from normal and appropriate for gestational age pregnancies (P<0.05). The binding to placentas from pregnancies complicated by White class AB diabetes or large for gestational age infants, on the other hand, was not significantly different from that to placentas from normal and appropriate for gestational age pregnancies. /sup 125/I-hEGF specific binding did not differ between placentas from intrauterine growth retarded or twin pregnancies (P<0.05). Placental and fetal membrane /sup 125/I-hEGF binding did not vary with fetal sex, maternal race, placental weight, or gestational age between 37 to 42 weeks (P<0.05). Placental but not fetal membrane /sup 125/I-hEGF binding increased with increasing infant weight when appropriate for gestational age and large for gestational age infants were included (P<0.05, r = 0.38, N = 32) but not for intrauterine growth retarded, appropriate for gestational age, or large for gestational age infants alone.
N-[2-(4-iodophenyl)ethyl]-N-methyl-2-(1-piperidinyl)ethylamine, IPEMP, and the corresponding bromo derivative, BrPEMP, have been synthesized and characterized. Both BrPEMP and IPEMP were evaluated for sigma-1 and sigma-2 subtype receptor affinities and found to possess very high affinities for both receptor subtypes. The precursor for radioiodination n-tributylstannylphenylethylpiperidinylethylamine was prepared from its bromo derivative by palladium-catalyzed stannylation reaction. Radioiodinated 4-[{sup 125}I]PEMP was readily prepared in high yields and high specific activity by oxidative iododestannylation reaction using chloramine-T as oxidizing agent. Sites labeled by 4-[{sup 125}I]PEMP in guinea pig brain membranes showed high affinity for BD1008, haloperidol, and (+)-pentazocine (Ki = 5.06 {+-} 0.40, 32.6 {+-} 2.75, and 48.1 {+-} 8.60 nM, respectively), which is consistent with sigma receptor pharmacology. Competition binding studies of 4-[{sup 125}I]PEMP in melanoma (A375) and MCF-7 breast cancer cells showed a high affinity, dose-dependent inhibition of binding with known sigma ligand N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl) ethylamine, BD1008 (Ki = 5, 11 nM, respectively), supporting the labeling of sigma sites in these cells. Haloperidol, however showed a weaker (Ki 100-200 nM) affinity for the sites labeled by 4-[{sup 125}I]PEMP in these cells. Biodistribution studies of 4-[{sup 125}I]PEMP in rats showed a fast clearance of this radiopharmaceutical from blood, liver, lung, and other organs. A co-injection of 4-IPEMP with 4-[{sup 125}I]PEMP resulted in 37%, 69%, and 35% decrease in activity in liver, kidney, and brain (organs possessing sigma receptors), respectively at 1-h postinjection. These results suggest that 4-[{sup 125}I]PEMP is a promising radiopharmaceutical for pursuing further studies in animal models with tumors.
Integrins are family of heterodimeric cell surface adhesion receptors able to recognize and bind to proteins in the extracellular matrix (ECM). This recognition is mainly through the RGD domain present in both the cell surface as the protein in the ECM. Various integrins have been identified as regulators of tumor progression. The RGD domain is also found in some snake venoms named disintegrins. Disintegrins inhibit cell-matrix and a cell-cell interaction mediated by integrin and has been shown that these proteins are able to inhibit metastasis in processes dependent on integrin. The disintegrin-like (ECD), as well as RGD-disintegrin are also able to bind to cell surface integrins and inhibit their adherence to the natural ligands. Leucurolysin-B (Leuc-B) is a metalloproteinase class P-III isolated from Bothrops leucurus (BLV) and possesses a disintegrin-like domain (ECD). The goals of this work were to synthesize a radioactive probe analog to Leuc-B using radioiodine {sup 125}I and evaluate the interaction of {sup 125}I-Leuc-B in tumor cells through the study of biodistribution in animals bearing Ehrlich tumor.125I-Leuc-B was synthesized using lactoperoxidase with high yield (90%) and specific activity of 1.2x10-7Bq/mmol. It was observed that {sup 125}I-Leuc-B had very fast clearance from the blood stream (T1/2= 0.01 h). Tumor uptake of 125I-Leuc-B gradually increased up to (2 min) and remained for a quite long period. The tumor/normal tissue uptake ratios of {sup 125}I-Leuc-B were 1.77 (tumor/normal paw) and 8.44 tumor/skeletal muscle. The results suggest that {sup 125}I-Leuc- B may constitute a good template for development of a tool for detection of solid tumors. (author)
Binding of apolipoprotein A-I and apolipoprotein A-IV to cultured bovine aortic endothelial cells
Adult bovine aortic endothelial (ABAE) cells specifically bound /sup 125/I-labelled high density lipoprotein3 (/sup 125/I-HDL3), and saturation of the binding was observed at a concentration of about 50 to 100 micrograms protein/ml. The binding of purified apolipoproteins (apo) A-I and A-IV to cultured ABAE cells and the correlation of this binding with the binding of HDL to the cells was studied. ABAE cells bound /sup 125/I-labelled apo A-I (/sup 125/I-apo A-I) and after a 3-hour exposure to the ligand, most of the radioactivity (82%) was associated with the cell surface and was accessible for trypsinization. Saturation of /sup 125/I-apo A-I binding was observed at a concentration of 3 micrograms/ml; each cell possessed 1.38 X 10(5) high affinity binding sites (Kd = 2.04 X 10(-8) M). The cultures also bound /sup 125/I-labelled apo A-IV (/sup 125/I-apo A-IV), and saturation of the binding was observed at a concentration of 2 micrograms/ml. Each cell possessed 5.4 X 10(4) high affinity binding sites for apo A-IV (Kd = 1.45 X 10(-8) M). Addition of either excess unlabelled apo A-I or excess unlabelled apo A-IV competed with the binding of both iodinated apo A-I and apo A-IV. It suggests that apo A-I and A-IV share the same binding site on endothelial cells. HDL also successfully competed with the binding of apo A-I and A-IV to ABAE cells.
Abstract in portuguese INTRODUÇÃO: Distúrbios do sistema de condução cardíaco são complicações potenciais e conhecidas dos procedimentos de cirurgia cardíaca valvar. OBJETIVOS: Investigar a associação entre fatores peri-operatórios com bloqueio atrioventricular (BAV) e a necessidade de estimulação cardíaca artificial temporária (ECAT) e, se necessário, implante de marcapasso definitivo no pós-operatório de cirurgia cardíaca (POCC) valvar. MÉTODOS: Coorte histórica de paci (more) entes submetidos a cirurgia cardíaca valvar, sendo realizada análise de banco de dados por regressão logística. RESULTADOS: No período de janeiro de 1996 a dezembro de 2008, foram realizadas 1102 cirurgias cardíacas valvares: 718 (65,2%) na valva aórtica e 407 (36,9%) na valva mitral; destas, 190 (17,2%) cirurgias de revascularização miocárdica associadas à cirurgia valvar e 23 (2,1%) cirurgias valvares combinadas (aórtica+mitral). Cento e oitenta e sete (17%) pacientes apresentaram quadro clínico e eletrocardiográfico de BAV durante o POCC valvar, necessitando de ECAT. Quatorze (7,5%) pacientes evoluíram para implante de marcapasso definitivo (1,27% do total da amostra). A análise multivariada evidenciou associação significativa de BAV com cirurgia de valva mitral (OR=1,76; IC 95% 1,08-2,37; P=0,002), implante de prótese biológica (OR=1,59; IC 95% 1,02-3,91; P= 0,039), idade maior que 60 anos (OR = 1,99; IC 95% 1,35-2,85; P Abstract in english INTRODUCTION: Disturbances of the cardiac conduction system are potential complications after cardiac valve surgery. OBJECTIVES: This study was designed to investigate the association between perioperative factors and atrio-ventricular block, the need for temporary cardiac artificial pacing and, if necessary, permanent pacemaker implantation after cardiac valve surgery. METHODS: Retrospective analysis of the Cardiac Surgery Database - Hospital São Lucas/PUCRS. The data a (more) re collected prospectively and analyzed retrospectively. RESULTS: Between January 1996 and December 2008 were included 1102 valve surgical procedures: 718 aortic valves (65.2%), 407 (36.9%) mitral valve and 190 (17.2%) coronar artery bypass grafting combined with valve repair and 23 (2.1%) aortic and mitral combined surgery. 187 patients (17%) showed clinical and electrocardiographic pattern of atrio-ventricular block requiring artificial temporary pacing. Of these, 14 patients (7.5%) required permanent pacemaker implantation (1.27% of the total valve surgery patients). Multivariate analysis showed association of the incidence of atrio-ventricular block and temporary pacing with mitral valve surgery (OR 1,76; CI 95% 1.08-2.37; P=0.002), implantation of bioprosthetic devices (OR 1.59; CI 95% 1.02-3.91; P=0,039), age over 60 years (OR 1.99; CI 95% 1.352.85; P
Sacral nerve stimulation for urinary dysfunction: the first year of the Scottish national service.
Sacral nerve stimulation (SNS) has become an established treatment option for patients with intractable detrusor overactivity and non-obstructive urinary retention. The Scottish Sacral Nerve Stimulation service was established in April 2010 to provide a service for the population of Scotland. We report our experience from the first year of this new national service. All patients referred for SNS from the inception of the service in April 2010 until the end of March 2011 were studied. During the one-year period, there were 50 referrals. Thirty-three percutaneous nerve evaluations, eight tined lead tests and 16 permanent implantation procedures were performed during this period. Morbidity was low and both incontinence and quality-of-life questionnaires demonstrated statistically significant improvements (International Consultation on Incontinence Questionnaire [ICIQ-SF], P = 0.005; Incontinence Impact Questionnaire [IIQ 7], P = 0.0007; Urogenital Distress Inventory [UDI 6], P = 0.0002). Referral pattern was skewed towards the west of Scotland with some health boards producing no referrals during the year. Results from the first year of the service have shown that it is a safe and efficient procedure with significant improvement in incontinence, voluntary voiding and quality-of-life parameters. The limitation of funding for permanent implants inevitably impacts on the role of the technique as a management option in these patients. PMID:23138579
For prostate cancer treatments, there is an increasing interest in the permanent radioactive seeds implant technique. Currently, in Brazil, the seeds are imported at high prices, which prohibit their use in public hospitals. One of the seed models that have been developed at CDTN has a ceramic matrix as a radioisotope carrier and a radiographic marker; the seed is encapsulated with biocompatible polymer. In this work, Monte Carlo simulations were performed in order to assess the dose distributions generated by the prototype seed model. The obtained data was assessed as described in the TG-43U1 report by the AAPM. The dosimetric parameters dose rate constant, {Lambda}, radial dose function, g{sub L}(r), and anisotropy function, F(r,{theta}), were derived from simulations using the MCNP5 code. The function g(r) shows that the seed has a lower decrease in dose rate on its transverse axis when compared to the 6711 model (one of the most used seeds in permanent prostate implants). F(r,{theta}) shows that CDTN's seed anisotropy curves are smoother than the 6711 model curves for {theta}{<=}20 deg and 0.25{<=}r{<=}1 cm. As well, the {Lambda} value is 15% lower than the {Lambda} value of 6711. The results show that CDTN's seed model can deposit a more isotropic dose. Because of the model's characteristics, the seeds can be impregnated with iodine of lower specific activity which would help reducing costs. (author)
A survey of research activity on nanoparticles (NPs) based on polymeric devices that could cross the blood-brain barrier (BBB) is given along with the presentation of our own data on the development of NPs of n-butyl-2-cyanoacrylate (BCA) for brain delivery to aid the early diagnosis of Alzheimer's disease (AD), a neurodegenerative disorder of the elderly people, the most prevalent form of dementia. Typical data are presented on in vivo detection of amyloid peptides (A beta) (amyloid plaques) that are used as targets for developing the biological markers for the diagnosis of AD. In order to develop efficient in vivo probes, polymeric n-butyl-2-cyanoacrylate (PBCA) NPs have been prepared and encapsulated with the radio-labeled amyloid affinity drug (125)I-clioquinol (CQ, 5-chloro-7-iodo-8-hydroxyquinoline) to improve the transport to brain and amyloid plaque retention of (125)I-CQ using the NPs of PBCA. The (125)I-CQ discriminately binds to the AD post-mortem brain tissue homogenates versus control. (125)I-CQ-PBCA NPs labeled the A beta plaques from the AD human post-mortem frontal cortical sections on paraffin-fixed slides. Storage phosphor imaging verified preferential uptake by AD brain sections compared to cortical control sections. The (125)I-CQ-PBCA NPs crossed the BBB in wild type mouse, giving an increased brain uptake measured in terms of % ID/g i.e., injected dose compared to (125)I-CQ. Brain retention of (125)I-CQ-PBCA NPs was significantly increased in the AD transgenic mice (APP/PS1) and in mice injected with aggregated A beta 42 peptide versus age-matched wild type controls. The results of this study are verified by in vivo storage phosphor imaging and validated by histopathological staining of plaques and select metal ions, viz. Fe(2+) and Cu(2+). The (125)I-CQ-PBCA NPs had more efficient brain entry and rapid clearance in normal mice and enhanced the retention in AD mouse brain demonstrating the ideal in vivo imaging characteristics. The (125)I-CQ-PBCA NPs exhibited specificity for A beta plaques both in vitro and in vivo. This combination offered radio-iodinated CQ-PBCA NPs as the promising delivery vehicle for in vivo single photon emission tomography (SPECT) ((123)I) or PET ((124)I) amyloid imaging agent. The importance of the topic in relation to brain delivery and other similar type of work published in this area are covered to highlight the importance of this research to medical disciplines. PMID:20049829
Increased Receptor Binding by Bovine (b) TSH Bound to Monoclonal Antibody to bTSH?-subunit
TSH receptor (R) binding and cAMP production by bovine (b) TSH-bound to a monoclonal antibody (MoAb) or polyclonal antibody (Ab) to bTSH were examined, using TSH receptor (R) coating tube and porcine thyroid cells. 125 I-bTSH bound-to MoAbs to bTSH(?) or discontinuous type MoAb showed TSHR binding (10%) similar to intact 125 I-bTSH. TSHR binding was completely decreased (<2%) when 125 I-bTSH was bound by polyclonal Abs to bTSH(?) in Graves' patient or rabbit polyclonal Abs to bTSH. When either of the two MoAb (No. 1 and 2) to bTSH(?) was bound to 125 I-bTSH, TSHR binding was 4 times higher (40%) compared to intact 125 I-bTSH. Binding of another MoAb (No. 3) caused no increased binding. TSHR binding of intact 125 I-bTSH was decreased from 10% to 2% by excess amounts of bTSH. Binding of 125 I-bTSH bound to MoAb to bTSH(?) (No. 1 and 2) decreased from 40% to 30% by excess amounts of bTSH. When 125 I-bTSH bound-Fab of MoAb was used, the binding was reduced from 30 to 10% (No. 1) and from 25 to 6% (No. 2), respectively. In contrast, cAMP production by bTSH was decreased by pre-binding of all MoAbs and polyclonal Abs. Binding of 125 I-MoAb to bTSH (?) to a synthetic peptide array of bTSH (?) sequence was examined by the radioautography. The epitope of MoAb to bTSH(?) was suggested to be LPK (? 42-44) for No. 1, KLF (? 39-41) for No. 2 and PKYA (? 43-46) for No. 3, respectively, although the existence of discontinuous epitope could not be ruled out. The increased TSHR binding and the decreased cAMP production by bTSH bound to MoAbs may be due to the conformational change of TSH molecule or TSHR by binding of both bTSH and MoAb.
Increased Receptor Binding by Bovine (b) TSH Bound to Monoclonal Antibody to bTSH?-Subunit
TSH receptor (R) binding and cAMP production by bovine (b) TSH-bound to a monoclonal antibody (MoAb) or polyclonal antibody (Ab) to bTSH were examined, using TSH receptor (R) coating tube and porcine thyroid cells. 125 I-bTSH bound-to MoAbs to bTSH(?) or discontinuous type MoAb showed TSHR binding (10%) similar to intact 125 I-bTSH. TSHR binding was completely decreased (<2%) when 125 I-bTSH was bound by polyclonal Abs to bTSH(?) in Graves_f patient or rabbit polyclonal Abs to bTSH. When either of the two MoAb (No. 1 and 2) to bTSH(?) was bound to 125 I-bTSH, TSHR binding was 4 times higher (40%) compared to intact 125 I-bTSH. Binding of another MoAb (No. 3) caused no increased binding. TSHR binding of intact 125 I-bTSH was decreased from 10% to 2% by excess amounts of bTSH. Binding of 125 I-bTSH bound to MoAb to bTSH(?) (No. 1 and 2) decreased from 40% to 30% by excess amounts of bTSH. When 125 I-bTSH bound-Fab of MoAb was used, the binding was reduced from 30 to 10% (No. 1) and from 25 to 6% (No. 2), respectively. In contrast, cAMP production by bTSH was decreased by pre-binding of all MoAbs and polyclonal Abs. Binding of 125 I-MoAb to bTSH (?) to a synthetic peptide array of bTSH (?) sequence was examined by the radioautography. The epitope of MoAb to bTSH(?) was suggested to be LPK (? 42-44) for No. 1, KLF (? 39-41) for No. 2 and PKYA (? 43-46) for No. 3, respectively, although the existence of discontinuous epitope could not be ruled out. The increased TSHR binding and the decreased cAMP production by bTSH bound to MoAbs may be due to the conformational change of TSH molecule or TSHR by binding of both bTSH and MoAb.
Nanodosimetry of (125)I Auger electrons.
Purpose: The nanodosimetric description of the radiation action of Auger electrons on nitrogen targets of nanometric size is presented. Materials and methods: Experimental microdosimetry at nanometer scale for Auger electrons has been accomplished with the set-up called Jet Counter. This consists of a pulse-operated valve which injects an expanding nitrogen jet into an interaction chamber where a gaseous sensitive volume of cylindrical shape is created. The ionization cluster size distributions (ICSD) created by Auger electrons emitted by (125)I while crossing a nanometer-sized volume have been measured. Results: The ICSD for the sensitive volumes corresponding to 3 and 12 nm in diameter (in unit density 1 g/cm(3)) irradiated by electrons emitted by a (125)I source were collected and compared with the corresponding Monte Carlo (MC) simulation. The preliminary results of the experiments with Auger electrons of (125)I interacting with a nitrogen jet having nanometric size comparable to a deoxyribonucleic acid (DNA) and nucleosome, showing the discrete spectrum of ICSD with extended cluster size, are described. Conclusions: The presented paper describes for the first time the nanodosimetric experiments with Auger electrons emitted by (125)I. A set of the new descriptors of the radiation quality describing the radiation effect at nanometer level is proposed. The ICSD were determined for the first time for an Auger emitter of (125)I. PMID:22934925
Purpose: The response of 2-amino-4-([{sup 14}C]methylthio)butyric acid ([{sup 14}C]Met) uptake and [{sup 125}I]3-iodo-alpha-methyl-L-tyrosine ([{sup 125}I]IMT) uptake to radiotherapy of C10 glioma cells was compared to elucidate the intracellular reactions that affect the response of 2-amino-4-([{sup 11}C]methylthio)butyric acid ([{sup 11}C]Met) uptake to radiotherapy. Methods: After irradiation of cultured (3 Gy) or xenografted C10 glioma cells (25 Gy) using a carbon ion beam, the accumulation of [{sup 14}C]Met and [{sup 125}I]IMT in the tumors was investigated. The radiometabolites in xenografted tumors after radiotherapy were analyzed by size-exclusion HPLC. Results: [{sup 14}C]Met provided earlier responses to the carbon ion beam irradiation than [{sup 125}I]IMT in both cultured and xenografted tumors. While [{sup 125}I]IMT remained intact in xenografted tumor before and after irradiation, the radioactivity derived from [{sup 14}C]Met was observed both in high molecular fractions and intact fractions, and the former decreased after irradiation. Conclusion: The earlier response of [{sup 11}C]Met uptake to tumor radiotherapy could be attributable to the decline in the intracellular energy-dependent reactions of tumors due to radiotherapy.
A series of iodinated analogues of MD-230254 was synthesized and evaluated for inhibitory potency and selectivity toward monoamine oxidase B (MAO-B). Among them, 5-[4-(2-iodobenzyloxy)phenyl]-3-(cyanoethyl)-1, 3, 4-oxadiazole-2(3H)one (2-IBPO) was found to have high inhibitory potency and selectivity toward MAO-B (IC50=2.0 nM, MAO-A/MAO-B >50000). Analysis of the inhibition kinetics indicated that 2-IBPO acts in a two-step mechanism as a competitive, slow, and tight-binding inhibitor of MAO-B with a Ki value of 2.4 nM and an overall Ki* value at an equilibrium of 3.8 nM. The new radioligand for MAO-B, [125I]2-IBPO was conveniently synthesized from a tributylstannyl precursor by an iododestannylation reaction using sodium [125I]iodide and hydrogen peroxide with high radiochemical yield. The in vivo tissue distribution studies of [125I]2-IBPO demonstrated its high initial uptake and prolonged retention in the brain. A selective interaction of [125I]2-IBPO with MAO-B was confirmed by the pretreatment experiment with well known MAO specific inhibitors, l-deprenyl, Ro-16-6491, clorgyline, and Ro-41-1049. These very desirable characteristics of [125I]2-IBPO suggested that a 123I-labeled counterpart, [123I]2-IBPO, would have great potential in in vivo studies of MAO-B in the human brain with single photon emission computed tomography (SPECT).
High-affinity receptors for bombesin-like peptides in normal guinea pig lung membranes
The binding of the radiolabeled bombesin analogue ({sup 125}I-Tyr{sup 4})bombesin to guinea-pig lung membranes was investigated. Binding of ({sup 125}I-Tyr{sup 4})bombesin was specific, saturable, reversible and linearly related to the protein concentration. Scatchard analysis of equilibrium binding data at 25C indicated the presence of a single class of non-interacting binding sites for bombesin (B{sub max} = 7.7 fmol/mg protein). The value of the equilibrium dissociation constant (K{sub D} = 90 pM) agrees with a high-affinity binding site. Bombesin and structurally related peptides such as ({sup 125}I-Tyr{sup 4})bombesin, neuromedin B and neuromedin C inhibited the binding of ({sup 125}I-Tyr{sup 4})bombesin in an order of potencies as follows: ({sup 125}I-Tyr{sup 4})bombesin {gt} bombesin {ge} neuromedin C {much gt} neuromedin B. These results indicate that guinea-pig lung membranes possess a single class of bombesin receptors with a high affinity for bombesin and a lower one for neuromedin B.
Single doses of acrylamide reduce retrograde transport velocity
Single doses of acrylamide (0-1.3 mmol/kg) produced a dose-dependent decrease in the transport of /sup 125/I-tetanus toxin to the perikarya of sensory neurons in dorsal root ganglia and motor neurons in ventral spinal cord. Acrylamide was a more potent inhibitor of retrograde transport in sensory axons than in motor axons. Substantially greater doses of N,N'-methylene-bis-acrylamide, a reportedly non-neurotoxic analog of acrylamide, were required to alter the axonal transport of /sup 125/I-tetanus toxin. Velocity of retrograde transport was assessed by determining the position of the leading edge of transported /sup 125/I-tetanus toxin at times following single doses of acrylamide. Acrylamide reduced the velocity of /sup 125/I-tetanus toxin transport in a dose-dependent manner by up to 75%. No change in neuronal uptake of /sup 125/I-tetanus toxin was detected. It is concluded that single doses of acrylamide produce profound alterations in retrograde transport which precede the appearance of structural changes in affected nerve fibers.
A series of iodinated analogues of MD-230254 was synthesized and evaluated for inhibitory potency and selectivity toward monoamine oxidase B (MAO-B). Among them, 5-[4-(2-iodobenzyloxy)phenyl]-3(cyanoethyl)-1,3,4-oxadiazole-2(3H)one (2-IBPO) was found to have high inhibitory potency and selectivity toward MAO-B (IC{sub 50}=2.0 n{sub M}, MAO-A/MAO-B>50000). Analysis of the inhibition kinetics indicated that 2-IBPO acts in a two-step mechanism as a competitive, slow, and tight-binding inhibitor of MAO-B with a Ki value of 2.4 n{sub M} and an overall Ki value at an equilibrium of 3.8 n{sub M}. The new radioligand for MAO-B, [{sup 125}I]2-IBPO was conveniently synthesized from a tributylstannyl precursor by an iododestannylation reaction using sodium [{sup 125}I]iodide and hydrogen peroxide with high radiochemical yield. The in vivo tissue distribution studies of [{sup 125}I]2-IBPO demonstrated its high initial uptake and prolonged retention in the brain. A selective interaction of [{sup 125}I]2-IBPO with MAO-B was confirmed by the pretreatment experiment with well known MAO specific inhibitors, l-deprenyl, Ro-16-6491, clorgyline, and Ro-41-1049. These very desirable characteristics of [{sup 125}I]2-IBPO suggested that a {sup 123}I-labeled counterpart, [{sup 123}I]2-IBPO, would have great potential in vivo studies of MAO-B in the human brain with single photon emission computed tomography (SPECT). (author)
Radionuclide imaging of experimental atherosclerosis with nonspecific polyclonal immunoglobulin G
The utility of nonspecific polyclonal IgG for external imaging of experimental atherosclerosis was tested in a series of rabbits after balloon catheter deendothelialization of the abdominal aorta. Following injection of /sup 111/In-IgG, /sup 111/In-Fc, or /sup 111/In-Fab serial images were recorded. In addition, several animals received /sup 125/I-low density lipoproteins (/sup 125/I-LDL), or /sup 125/I human serum albumin (/sup 125/I-HSA) as positive and negative controls. Forty-eight hours after injection of the radiolabeled proteins, the aortas were removed, divided into abdominal and thoracic regions, counted, and autoradiographed. The images acquired after injection of /sup 111/In-IgG and /sup 111/In-Fc, showed clear focal accumulation of radioactivity in the healing abdominal aorta. In contrast, the images obtained after injection of /sup 111/In-Fab did not show focal radionuclide accumulation. For /sup 111/In-IgG and /sup 111/In-Fc there were three to six times as many counts in the abdominal as in the thoracic aorta, while for /sup 111/In-Fab and /sup 125/I HSA, the abdominal and thoracic counts were nearly equal. The results suggest that radiolabeled IgG and Fc can be used to image experimental atherosclerosis.
We examined the fate of C component C3 on the surface of Salmonella typhimurium during ingestion by human neutrophils. Initial experiments showed that C3 fragments and C3-acceptor complexes were the major serum ligands which were surface iodinated by canine myeloperoxidase on serum-incubated rough and smooth isolates of S. typhimurium. In contrast, labeled C3 was not identified when the same organisms were ingested by neutrophils in the presence of 125I-Na, a situation previously shown to iodinate particulate targets via the neutrophil myeloperoxidase-halide-H2O2 system. Pretreatment of neutrophils before phagocytosis with the lipid-soluble protease inhibitor diisopropylfluorophosphate (DFP), but not with other protease inhibitors (p-nitrophenylguanidinobenzoate, leupeptin, pepstatin), substantially blocked proteolysis of 125I-C3 on S. typhimurium strain RG108 during ingestion by neutrophils. Purification of neutrophil phagosomes containing S. typhimurium-bearing 125I-C3 showed that DFP but no other protease inhibitors blocked proteolysis of 125I-C3 within phagosomes. Iodinated C3-acceptor complexes were identified by immunoprecipitation from the detergent-insoluble fraction of phagosomes prepared from DFP-treated cells ingesting S. typhimurium in the presence of 125I-Na. These results show that C3 fragments on the surface of S. typhimurium are the major serum ligands which are halogenated and degraded by proteolysis during phagocytosis by human neutrophils, and suggest that the majority of proteolysis on the ingested target occurs within the neutrophil phagosome.
We investigated the receptor localization of atrial natriuretic peptide (ANP) in the rat kidney, by in vitro macro- and micro-autoradiography (ARG) of (/sup 125/I)-ANP using nonfixed frozen sections. First, we examined the optimum conditions for ARG with respect to the effects of polyethylenimine (PEI), thickness of section, incubation time and degradation of (/sup 125/I)-ANP. Saturation experiments of (/sup 125/I)-ANP using rat kidney sections revealed the presence of high affinity binding sites of (/sup 125/I)-ANP in the renal cortex (Kd = 0.52 nM). Macro-autoradiograms showed that the dense grains representing specific binding sites of (/sup 125/I)-ANP were distributed in the cortex in a punctate pattern. Using micro-autoradiography, the localization of the dense grains on the emulsion was compared with the staining pattern of the same section subjected to double staining. In the renal cortex, the dense grains were observed on the glomerulus, blood vessels and proximal tubules. Dense grains were also observed in the mesangium area of glomeruli, the inside wall of blood vessels (especially endothelium), and the inside wall of proximal tubules (possibly brush border). These results suggested that the physiological action of ANP in the kidney is mediated by its receptors. Also, ARG was useful for accurately detecting the action sites of ANP.
(/sup 125/I)- and (/sup 131/I)thyroglobin (Tg) tracer obtained by two different oxidation methods, chloramine-T (ChlT) and lactoperoxidase (LP-ase), were analyzed to assess their suitability in the development of a RIA. Pairs of tracers which were prepared on a single day using these methods with a single source of /sup 131/I and /sup 125/I were compared. The following conclusions were reached. (1) Both /sup 131/I and /sup 125/I isotopes, using Chl-T or LP-ase as oxidants, produce suitable tracers. (2) (/sup 131/I)Tg can be used repeatedly for 2 weeks without repurification. (3) (/sup 125/I)Tg, in contrast, has to be rechromatographed weekly on sephadex G-200 to maintain assay sensitivity and adequate maximal binding. (4) Under these conditions, 2- or 9-day tracers with either isotope using Chl-T or LP-ase give similar Tg determinations in the serum. (5) The LP-ase-chromatographed /sup 125/I tracer seems to lead to higher maximal binding in the assay than the Chl-T-repurified tracer.
/sup 125/I-spiperone: a novel ligand for D/sub 2/ dopamine receptors
/sup 125/I-Spiperone binds with high affinity K/sub D/ 0.3 nM) to a single specific site (B/sub max/ 34 pmole/g wet weight) in homogenates of rat corpus striatum. Specific binding is about 40-60 percent of total binding and is displaced stereo-specifically by butaclamol and clopenthixol. Neuroleptic drugs of various classes are potent inhibitors of /sup 125/I-spiperone binding (/sub i/'s 1-10 nM). Selective dopamine antagonists such as sulpiride (K/sub i/ 50 nM) and dopamine agonists such as apomorphine (K/sub i/ 200 nM) are also potent inhibitors. The drugs specificity of /sup 125/I-spiperone binding correlates well with that of /sup 3/H-spiperone binding, providing good evidence that /sup 125/I-spiperone labels D/sub 2/ dopamine receptors in striatal membranes. /sup 125/I-Spiperone, with its high specific activity (2200 Ci/mmol) may prove to be a useful ligand in studies examining D/sub 2/ dopamine receptors in soluble preparations and by autoradiography. Furthermore iodinated spiperone may be useful in radioreceptor assays of neuroleptic drug levels and, in a /sup 123/I-labeled form for imaging of dopamine receptors, in vivo, using single photon tomography. 18 references, 4 figures, 1 table.
Standardization of 125I and 109Cd by the photon-photon coincidence method in PTKMR-BATAN.
A photon-photon coincidence system was constructed for the standardization of (125)I and (109)Cd in PTKMR-BATAN, Indonesia. Two NaI(Tl) detectors of 76 mm diameter × 6mm thickness with 0.5mm aluminum window were used, which were positioned approximately symmetrically to the source holder. The electronic chain was almost the same as for a 4??-? system. The CANBERRA Multiport II multi channel analyzer was used for energy calibration and a Philips type PM3092 oscilloscope for visualization of the pulses. A polyethylene plastic was used as the source substrate for the (125)I and (109)Cd samples. The activity of a (125)I solution was measured by the photon-photon coincidence and the efficiency extrapolation method (Schrader and Walz, 1987), whereas the activity of a (109)Cd solution was determined by a tracer method using (125)I (Schrader, 2006). The result of the (125)I activity showed good agreement with the result of measurements using a calibrated ionization chamber, and the result of (109)Cd also showed good agreement with the measurements result using a LEGe detector. PMID:22484138
Exploring the binding site of acetogenin in the ND1 subunit of bovine mitochondrial complex I.
125I-labeled (trifluoromethyl)phenyldiazirinyl acetogenin, [125I]TDA, a photoaffinity labeling probe of acetogenin, photo-cross-links to the ND1 subunit of bovine heart mitochondrial NADH-ubiquinone oxidoreductase (complex I) with high specificity [M. Murai, A. Ishihara, T. Nishioka, T. Yagi, and H. Miyoshi, (2007) The ND1 subunit constructs the inhibitor binding domain in bovine heart mitochondrial complex I, Biochemistry 46 6409-6416.]. To identify the binding site of [125I]TDA in the ND1 subunit, we carried out limited proteolysis of the subunit cross-linked by [125I]TDA using various proteases and carefully analyzed the fragmentation patterns. Our results revealed that the cross-linked residue is located within the region of the 4th to 5th transmembrane helices (Val144-Glu192) of the subunit. It is worth noting that an excess amount of short-chain ubiquinones such as ubiquinone-2 (Q2) and 2-azido-Q2 suppressed the cross-linking by [125I]TDA in a concentration-dependent way. Although the question of whether the binding sites for ubiquinone and different inhibitors in complex I are identical remains to be answered, the present study provided, for the first time, direct evidence that an inhibitor (acetogenin) and ubiquinone competitively bind to the enzyme. Considering the present results along with earlier photoaffinity labeling studies, we propose that not all inhibitors acting at the terminal electron transfer step of complex I necessarily bind to the ubiquinone binding site itself. PMID:19265669
(/sup 125/I) radioiodinated metaraminol: A new platelet-specific labeling agent
In our search for a platelet-specific labeling agent, metaraminol (MA), a low-toxic pharmaceutical for the treatment of hypotension and cardiogenic shock, attracted our attention. Its active incorporation and accumulation by platelets have been recognized. At first, the preparation of /sup 125/I radioiodinated metaraminol (/sup 125/I-MA) was carried out using the chloramine-T method. Then, upon the harvest of platelets as platelet-rich plasma (PRP), their labeling with this new radiopharmaceutical was easily performed by incubation for 10 min at 37/sup 0/C. The cell-labeling efficiency was dependent on cell density, reaching 63.0%+-3.1% at 2.4x10/sup 9/ cells/ml. The specific incorporation of /sup 125/I-MA by an active transport system similar to that of 5-hydroxytryptamine (5-HT) as well as by passive diffusion was demonstrated. In vitro studies, the unaltered state of /sup 125/I-MA-labeled platelets with their cellular functions fully retained was estimated. In vivo studies carried out in rabbits with induced thrombi in the femoral artery showed a rather rapid disappearance of the radioactivity from circulating blood, reaching a high thrombus-to-blood activity ratio of 19.8+-4.3 within 30 min of the administration of /sup 125/I-MA-labeled autologous platelets. Thus, with the potential availability of /sup 123/I, /sup 123/I-MA-labeled platelets appear to be a promising agent for thrombus imaging using single-emission computed tomography (CT) studies.
Cholecystokinin (CCK) is a gastrointestinal hormone which regulates gastric motility. The authors have characterized specific /sup 125/I-BH-CCK-8 binding in guinea pig stomach muscle membranes. The relative potencies of various CCK related peptides to inhibit specific /sup 125/I-CCK-8 binding in stomach muscle membranes resembled their rank order determined for pancreatic CCK receptor binding (CCK-8>> CCK-8-desulfate = gastrin CCK-4). The specific peripheral CCK antagonist, asperlicin and other non- selective CCK antagonists including proglumide, CBZ-CCK (26-32) amide, dibutyrylcyclic GMP and benzotript effectively inhibited /sup 125/I-CCK-8 binding in gastric muscle membranes with IC/sub 50/'s comparable to those for pancreatic CCK receptors. In contrast, specific /sup 125/I-CCK-8 binding in guinea pig gastric glands was inhibited equally well by gastrin and CCK-8. Moreover, asperlicin did not inhibit /sup 125/I-CCK-8 binding in guinea gastric glands. These results indicate CCK receptors in the stomach muscle membranes are similar to pancreatic CCK receptors but different from brain CCK or gastrin receptors.
The presence of N-terminally extended forms of neurokinin A has recently been reported in the mammalian brain. Among them, gamma-preprotachykinin-(72-92)-peptide amide (gamma-PPT-(72-92)-NH2), a peptide derived by posttranslational processing of gamma-preprotachykinin, is most prominent. We report here that this peptide most likely acts on neurokinin-2 receptor sites since neurokinin A (a putative neurokinin-2 agonist) and gamma-PPT-(72-92)-NH2 are potent competitors of 125I-labeled gamma-PPT-(72-92)-NH2 binding whereas selective neurokinin-1 and -3 agonists are not. Moreover, the distribution of 125I-labeled gamma-PPT-(72-92)-NH2 and 125I-labeled neurokinin A binding sites are very similar in rat brain. On the other hand, 125I-labeled Bolton-Hunter-substance P (a neurokinin-1 ligand) and 125I-labeled Bolton-Hunter-eledoisin (a neurokinin-3 ligand) binding sites are differentially located in this tissue. Thus, it appears that gamma-PPT-(72-92)-NH2 binds to neurokinin-2 receptors and should be considered as a putative endogenous ligand for this receptor class.
A radioiodinated derivative of the tumor-homing F3 peptide, (N-(2-{3-[125I]Iodobenzoyl}aminoethyl)maleimide-F3Cys peptide, [125I]IBMF3 was developed for investigation as a SPECT tumor imaging radioligand. For this purpose, we custom synthesized a modified F3 peptide analog (F3Cys) incorporating a C-terminal cysteine residue for site-specific attachment of a radioiodinated maleimide conjugating group. Initial proof-of-concept Fluorescence studies conducted with AlexaFluor 532 C5 maleimide-labeled F3Cys showed distinct membrane and nuclear localization of F3Cys in MDA-MB-435 cells. Additionally, F3Cys conjugated with NIR fluorochrome AlexaFluor 647 C2 maleimide demonstrated high tumor specific uptake in melanoma cancer MDA-MB-435 and lung cancer A549 xenografts in nude mice whereas a similarly labeled control peptide did not show any tumor uptake. These results were also confirmed by ex vivo tissue analysis. No-carrier-added [125I]IBMF3 was synthesized by a radioiododestannylation approach in 73% overall radiochemical yield. In vitro cell uptake studies conducted with [125I]IBMF3 displayed a 5-fold increase in its cell uptake at 4 h when compared to controls. SPECT imaging studies with [125I]IBMF3 in tumor bearing nude mice showed clear visualization of MDA-MB-435 xenografts on systemic administration. These studies demonstrate a potential utility of F3 peptide-based radioligands for tumor imaging with PET or SPECT techniques.
Strand breaks in plasmid DNA following positional changes of Auger-electron-emitting radionuclides
The purpose of our studies is to elucidate the kinetics of DNA strand breaks caused by low-energy Auger electron emitters in close proximity to DNA. Previously we have studied the DNA break yields in plasmids after the decay of indium-111 bound to DNA or free in solution. In this work, we compare the DNA break yields in supercoiled DNA of iodine-125 decaying close to DNA following DNA intercalation, minor-groove binding, or surface binding, and at a distance form DNA. Supercoiled DNA, stored at 4 C to accumulate radiation dose from the decay of {sup 125}I, was then resolved by gel electrophoresis into supercoiled, nicked circular, and linear forms, representing undamaged DNA, single-strand breaks, and double-strand breaks respectively. DNA-intercalated or groove-bound {sup 125}I is more effective than surface-bound radionuclide or {sup 125}I free in solution. The hydroxyl radical scavenger DMSO protects against damage by {sup 125}I free in solution but has minimal effect on damage by groove-bound {sup 125}I. (orig.).
Detecting aggregated amyloid peptides (Abeta plaques) presents targets for developing biomarkers of Alzheimer's disease (AD). Polymeric n-butyl-2-cyanoacrylate (PBCA) nanoparticles (NPs) were encapsulated with radiolabelled amyloid affinity (125)I-clioquinol (CQ, 5-chloro-7-iodo-8-hydroxyquinoline) as in vivo probes. (125)I-CQ-PBCA NPs crossed the BBB (2.3 +/- 0.9 ID/g) (P < .05) in the WT mouse (N = 210), compared to (125)I-CQ (1.0 +/- 0.4 ID/g). (125)I-CQ-PBCA NP brain uptake increased in AD transgenic mice (APP/PS1) versus WT (N = 38; 2.54 x 10(5) +/- 5.31 x 10(4) DLU/mm(2); versus 1.98 x 10(5) +/- 2.22 x 10(4) DLU/mm(2)) and in APP/PS1/Tau. Brain increases were in mice intracranially injected with aggregated Abeta(42) peptide (N = 17; 7.19 x 10(5) +/- 1.25 x 10(5) DLU/mm(2)), versus WT (6.07 x 10(5) +/- 7.47 x 10(4) DLU/mm(2)). Storage phosphor imaging and histopathological staining of the plaques, Fe(2+) and Cu(2+), validated results. (125)I-CQ-PBCA NPs have specificity for Abeta in vitro and in vivo and are promising as in vivo SPECT ((123)I), or PET ((124)I) amyloid imaging agents. PMID:20721294
To localize epidermal growth factor (EGF) receptors in normal human epidermis and other skin structures, two different light microscopic methods were used. EGF binding [( 125I]EGF/R) to the extracellular portion of the EGF receptor was studied by incubating intact skin samples with [125I]EGF, sectioning the tissues, and performing autoradiography. Immunoreactive EGF receptor molecules (IR-EGF/R) were localized with a mono-specific anti-EGF receptor antibody using a 2-step indirect immunocytochemical method (horseradish peroxidase) and detergent permeabilized tissues. This latter method measured the total pool of EGF receptors: occupied and/or internalized forms, precursor forms, and partially degraded forms of the EGF receptor that retain immunoreactivity. Both the [125I]EGF/R and IR-EGF/R localization studies indicated that EGF receptors were present in basal epidermal keratinocytes, sebocytes, outer root sheath cells in hair follicles, smooth muscle cells of arrector pili muscles, and dermal arteries. The highest levels of [125I]EGF/R and IR-EGF/R were found in the dermal ducts of eccrine sweat glands. The distribution of both [125I]EGF/R and IR-EGF/R was not consistent with the concept that EGF exclusively is involved in cellular division and proliferation in normal human epidermis and its appendages, i.e., EGF receptors were also found in tissues that do not undergo rapid proliferation. The present study indicates that EGF may have a more complex regulatory role in the skin than was previously thought. PMID:6092481
Abstract in portuguese INTRODUÇÃO: O implante percutâneo valvular aórtico é uma alternativa promissora no tratamento da estenose aórtica grave de pacientes com elevado risco cirúrgico. No entanto, parte desses pacientes pode desenvolver distúrbios do sistema de condução elétrico do coração e necessidade de implante de marca-passo permanente. O mecanismo das alterações do sistema de condução não está completamente elucidado. Nosso objetivo é avaliar a frequência e os fatores (more) relacionados à necessidade de marca-passo permanente em nosso meio. MÉTODO: Série de casos com descrição das variáveis absolutas e relativas associadas à necessidade de marca-passo permanente em pacientes submetidos a implante percutâneo valvular aórtico no Instituto de Cardiologia do Rio Grande do Sul. RESULTADOS: Entre novembro de 2008 e novembro de 2009, 10 pacientes foram submetidos a implante percutâneo valvular aórtico com prótese CoreValveTM. Excluíram-se da análise 2 pacientes que faleceram por complicações não associadas aos distúrbios do sistema de condução. Nos 8 pacientes restantes obteve-se sucesso do procedimento, com redução dos gradientes entre o ventrículo esquerdo e a aorta e melhora sintomática. A maioria era composta por mulheres (75%), com média de idade de 86 anos. Houve necessidade de marca-passo permanente em 6 pacientes (75%) pós-implante percutâneo valvular aórtico. O único fator relacionado foi o surgimento de bloqueio de ramo esquerdo. No seguimento clínico, 1 paciente reassumiu o ritmo sinusal, 2 alternam ritmo próprio com o do marcapasso e 3 permanecem dependentes do estímulo artificial, até o momento. CONCLUSÕES: Observou-se elevada necessidade de marca-passo permanente após implante percutâneo valvular aórtico e o surgimento de bloqueio de ramo esquerdo parece estar associado a essa ocorrência. Estudos adicionais com maior poder, comparativos com outras técnicas, são necessários para definir a exata incidência dos distúrbios de ritmo provocados pelo implante percutâneo valvular aórtico. Abstract in english BACKGROUND: Percutaneous aortic valve implantation (PAVI) is a promising alternative treatment for severe aortic stenosis in high surgical risk patients. However, part of these patients may develop electrical conduction system disturbances and require permanent pacemaker implantation. The mechanism of such electrical conduction system disturbances has not been totally elucidated. Our objective is to assess the frequency and factors related to the need of a permanent pacem (more) aker (PPM) in this scenario. METHOD: A series of cases describing absolute and relative variables associated to PPM implantation in patients submitted to PAVI at Instituto de Cardiologia do Rio Grande do Sul. RESULTS: Between November 2008 and November 2009, ten patients were submitted to PAVI using the CoreValveTM prosthesis. Two patients who died due to complications not associated to the conduction system disturbances were excluded. The procedure was successfully carried out in the eight remaining patients, with gradient reduction between the left ventricle and aorta and symptomatic relief. Most of the patients were women (75%) and mean age was 86 years. PPM was required in six patients (75%) after PAVI. The single procedure related event was the development of left bundle branch block (LBBB). During clinical follow-up, one patient resumed sinus rhythm, two alternated their own rhythm with the pacemaker rhythm and three remain totally dependent of artificial stimulus. CONCLUSIONS: We observed an increased need of PPM after PAVI and the development of LBBB seems to be associated to it. Additional and powered studies, comparing other techniques, are required to define the exact incidence of rhythm disturbances caused by PAVI.
In this study, we report a hybrid organic-inorganic TEOS-MTES (tetraethylorthosilicate-methyltriethoxysilane) sol-gel-made coating as a potential solution to improve the in vivo performance of AISI 316L stainless steel, which is used as permanent bone implant material. These coatings act as barriers for ion migration, promoting the bioactivity of the implant surface. The addition of SiO(2) colloidal particles to the TEOS-MTES sol (10 or 30 mol.%) leads to thicker films and also acts as a film reinforcement. Also, the addition of bioactive glass-ceramic particles is considered responsible for enhancing osseointegration. In vitro assays for bioactivity in simulated body fluid showed the presence of crystalline hydroxyapatite (HA) crystals on the surface of the double coating with 10mol.% SiO(2) samples on stainless steel after 30 days of immersion. The HA crystal lattice parameters are slightly different from stoichiometric HA. In vivo implantation experiments were carried out in a rat model to observe the osteointegration of the coated implants. The coatings promote the development of newly formed bone in the periphery of the implant, in both the remodellation zone and the marrow zone. The quality of the newly formed bone was assessed for mechanical and structural integrity by nanoindentation and small-angle X-ray scattering experiments. The different amount of colloidal silica present in the inner layer of the coating slightly affects the material quality of the newly formed bone but the nanoindentation results reveal that the lower amount of silica in the coating leads to mechanical properties similar to cortical bone. PMID:19835999
Purpose: To present a method for the dosimetric analysis of permanent prostate brachytherapy implants using a combination of stereoscopic X-ray radiography and magnetic resonance (MR) imaging (XMR) in an XMR facility, and to compare the clinical results between XMR- and computed tomography (CT)-based dosimetry. Methods and Materials: Patients who had received nonstranded iodine-125 permanent prostate brachytherapy implants underwent XMR and CT imaging 4 weeks later. Four observers outlined the prostate gland on both sets of images. Dose-volume histograms (DVHs) were derived, and agreement was compared among the observers and between the modalities. Results: A total of 30 patients were evaluated. Inherent XMR registration based on prior calibration and optical tracking required a further automatic seed registration step that revealed a median root mean square registration error of 4.2 mm (range, 1.6-11.4). The observers agreed significantly more closely on prostate base and apex positions as well as outlining contours on the MR images than on those from CT. Coefficients of variation were significantly higher for observed prostate volumes, D90, and V100 parameters on CT-based dosimetry as opposed to XMR. The XMR-based dosimetry showed little agreement with that from CT for all observers, with D90 95% limits of agreement ranges of 65, 118, 79, and 73 Gy for Observers 1, 2, 3, and 4, respectively. Conclusions: The study results showed that XMR-based dosimetry offers an alternative to other imaging modalities and registration methods with the advantages of MR-based prostate delineation and confident three-dimensional reconstruction of the implant. The XMR-derived dose-volume histograms differ from the CT-derived values and demonstrate less interobserver variability.
In 72 male rabbits aged 6 months, the endothelium of the abdominal aorta was abraded by a Fogarthy catheter. The animals were then fed a 1% cholesterol-supplemented diet for 4 weeks. In addition, half of the animals were treated for the entire period with isradipine (0.3 mg/kg daily), a dihydropyridine calcium antagonist; the other 36 animals served as controls. One hour and 3, 6, 12, 24, and 48 hours before the animals were killed, (125-I)low-density lipoprotein (LDL 10 microCi) was administered intravenously (i.v.) to six animals in each group. The (125-I)LDL entry was quantified in the abdominal aorta according to the type and presence of endothelial lining. Isradipine significantly reduced the (125-I)LDL entry at most time intervals. In parallel, an increase in vascular prostaglandin (PGI2) synthesis was noted, which might be the underlying mechanism for the decreased LDL entry.
A crossed radioimmunoelectrophoretic (CRIE) method for detection of specific IgG antibodies in patients' sera against horse hair and dander was developed. The unacceptably high non-specific binding encountered when substituting /sup 125/I-labelled antihuman IgG for /sup 125/I-labelled antihuman IgG in an ordinary CRIE was eliminated by the combined use of /sup 125/I-labelled Protein A as detector, and F(ab')/sub 2/-fragments of the allergen-specific rabbit antibodies. The low background binding thus obtained makes the method useful for detection of specific IgG in sera where the ratio between specific and non-specific IgG is low. Therefore the method should also be applicable to other antigen/allergen systems.
The specific radioactivity of conventionally prepared 125I IgG anti-D eluates is significantly less (from 1/5 to 1/20) than that of the 125I IgG fraction used to prepare the eluate. This discrepancy is due to the release of unlabeled, cytophilic IgG from normal red blood cells during eluate preparation and does not represent an underestimation of the eluate anti-D IgG content. Cytophilic IgG content of eluates plays an important role in reducing the nonimmunologic binding of labeled antibody IgG. The results justify the assumption used in numerous studies that the specific radioactivity of 125I IgG fractions can be used to provide a valid estimate of the anti-D IgG content of eluates.
Preparation of /sup 125/I-protein A usable for up to 10 months in immunoassays. [Long shelf life
Chloramine-T iodination of protein A from Staphylococcus aureus and gel electrophoretic purification of the iodination mixture results in a stable tracer of high specific and functional activity. Following repeated gel electrophoresis of the tracer only a single component was observed. The specific activity of the /sup 125/I-protein A was between 30 and 55 ..mu..Ci/..mu..g. The binding of /sup 125/I-protein A to rabbit immunoglobulin exceeded 90% and the tracer competed effectively with unlabelled protein A in binding to cells incubated with sera containing surface antibodies. Storage of the tracer for up to 46 weeks resulted in a moderate decrease in maximal binding to immunoglobulin (from 91% to 64%), in TCA precipitable radioactivity (from 97% to 80%) and an approx. 30% decrease in the ability to detect cell bound immunoglobulin. It is concluded that gel electrophoretic purification of /sup 125/I-protein A produces a tracer with a very long shelf life.
Variation in 125I-insulin absorption and blood glucose concentration
The absorption of monocomponent porcine 125I-insulin Monotard and Isophane was studied in six insulin dependent diabetic patients over a period of 12 days. The absorption of insulin was measured as the disappearance of radioactivity from sites of injection. The daily 125I-insulin doses ranged from 20 to 48 IU between patients. The insulin absorbed varied considerably within and between patients. The range of individual daily absorbed insulin varied from 19 to 104 per cent of the 125I-insulin dose. A significant correlation (p less than 0.05) was found between insulin absorption and blood glucose concentration. Insulin absorption rates were relatively high before all hypoglycaemic episodes and reactive hyperglycaemia was only observed when relatively low insulin absorption rates followed the hypoglycaemic attack. The results show that lability in some insulin dependent diabetics is explained by variation in insulin absorption.
A comparative study of performance of 19-iodo cholesterol {sup 1}25I 3-acetate and sodium iodide samples labeled with 125I is presented for liquid scintillation counting measurements. Quench effect, count rate stability and spectral evolution of samples have been followed for several weeks in Toluene, Hisafe II, Instagel, Dioxane-naphthalene and Toluene-alcohol scintillators. Organic samples have negligible quench effect in the interval of I concentration of 0-90 {mu}g and inorganic samples only show a very small variation, lower than 12%, for Dioxane-naphthalene, in the same range of concentration. Satisfactory stability is obtained in general for both, organic and inorganic samples, but small counting losses, 0.03% for 19-iodocholesterol 1 I 3-acetate samples in Tolue ne-alcohol and 0 .04% for Na 125I samples in Dioxane-naphthalene and Toluene-alcohol, have been reported. (Author) 8 refs.
Separation of 3H, 14C, 32P, 35S, 125I, and 131I in radioisotope waste
Measurement of 3H, 14C, 32P, 35S, 125I, and 131I in radioisotope (RI) waste materials such as the vials, pipette tips, tubes, syringes, and paper generated from the industrial, medical, educational, and research organizations were conducted by a wet oxidation method. Counts were obtained by a liquid scintillation counter for 3H, 14C, and 32P; a gas proportional counter for 35S; a low energy photon spectroscopy for 125I; and an HPGe detector for 131I. After the treatment of approximately 20?g of the sample, the counting value was determined to obtain a minimum detectable activity (MDA) of approximately 1??10?3?~?5??10?2?Bq/g. The specific activities of shor-half-life RIs (32P, 35S, 125I, and 131I) were not detectable and/or resulted in a low value (<1?Bq/g). The waste containing 3H and 14...
Introduction: Sigma-1 (@s"1) receptor radioligands are useful for basic pharmacology studies and for imaging studies in neurology, psychiatry and oncology. We derived a hybrid structure, N-1-allyl-N'-4-phenethylpiperazine, from known ligands TPCNE and SA4503 for use as a scaffold for development of radioiodinated @s"1 receptor ligands. Methods: E-and Z-N-1-(3'-iodoallyl)-N'-4-(3'',4''-dimethoxyphenethyl)-piperazine (E-1 and Z-1), N-1-allyl-N'-4-(3',4'-dimethoxyphenethyl)-piperazine (2) and E-N-1-(3'-iodoallyl)-N'-4-(3''-methoxy-4''-hydroxyphenethyl)-piperazine (3) were synthesized. Affinities for @s"1 and @s"2 receptors were determined. [^1^2^5I]E-1 and [^1^2^5I]Z-1 were prepared and evaluated in vivo in mice. [^1^2^5I]E-1 was further evaluated in @s"1 receptor binding assays in vitro. Res...
Abstract This study investigated the feasibility of targeting the free, unbound forms of prostate-specific antigen (fPSA) for in vivo imaging of prostate adenocarcinomas (PCa), as PSA is produced and secreted at abundance during every clinical stage and grade of PCa, including castration-resistant disease. We injected 125I-labeled monoclonal antibody PSA30 (specific for an epitope uniquely accessible on fPSA alone) intravenously in male nude mice carrying subcutaneous xenografts of LNCaP tumors (n=36). Mice were sacrificed over a time course from 4 hours to 13 days after injecting 125I-labeled PSA30. Tissue uptake of 125I-PSA30 at 48 and 168 hours after intravenous injection was compared with two clinically used positron emission tomography radiopharmaceuticals, 18F-fluoro-deoxy-glucose (1...
The presynaptically active snake venom neurotoxin ..beta..-bungarotoxin (..beta..-Butx) is known to affect neurotransmitter release by binding to a subtype of voltage-activated K/sup +/ channels. Here the authors show that mast cell degranulating (MCD) peptide from bee venom inhibits the binding of /sup 125/I-labeled ..beta..-Butx to chick and rat brain membranes with apparent K/sub i/ values of 180 nM and 1100 nM, respectively. The mechanisms of inhibition of MCD peptide is noncompetitive, as is inhibition of /sup 125/I-..beta..-Butx binding by the protease inhibitor homologue from mamba venom, toxin I. ..beta..-Butx and its binding antagonists thus bind to different sites of the same membrane protein. Removal of Ca/sup 2 +/ by ethylene glycol bis(..beta..-aminoethyl ether)-N,N,N',N'-tetraacetic acid inhibits the binding of /sup 125/I-..beta..-Butx by lowering its affinity to brain membranes.
Radioiodination and biological evaluation of salbutamol as a ?2-adrenoceptor agonist
A procedure for preparing high-radiochemical-purity 125I-salbutamol was developed in order to characterize the binding properties of ?2-adrenoceptors. Direct radioiodination of salbutamol was carried out using Chloramine T as an oxidizing agent. The optimized conditions for salbutamol labeling with 125I are as follows: 100 ?g of salbutamol, 50 ?g of Chloramine T, 150 ?l of phosphate buffer (pH 7), room temperature (25 ? 1?C), 5 min. The radiochemical yield of up to 98% was attained. The radiochemical yield and purity of the labeled product were evaluated by electrophoresis and HPLC. Biodistribution studies were carried out in normal Albino Swiss mice at different time intervals after administration of 125I-salbutamol. The results indicate that the labeled compound cleared from the systemat...
99mTc-albumin can replace 125I-albumin to determine plasma volume repeatedly
Abstract Objective. Plasma volume assessment may be of importance in several disorders. The purpose of the present study was to compare the reliability of plasma volume measurements by technetium-labeled human serum albumin (99mTc-HSA) with a simultaneously performed plasma volume determination with iodine-labeled human serum albumin (125I-HSA). Materials and methods. In 15 healthy volunteers, simultaneous plasma volume measurements with 99mTc-HSA and 125I-HSA were performed after 1/2 hour in the supine position. Blood samples were obtained 10, 15, 20, and 30 minutes after the injection for accurate retropolation from the plasma counts to time zero to correct for leakage of the isotopes from the circulation. Results. The mean difference (bias) between plasma volume measured with 125I-album...
Characterization and localization of a novel neuroreceptor for the peptide sarafotoxin
We have recently shown that the rat atrium and brain contain specific high affinity receptors for the novel snake vasoconstrictor peptide sarafotoxin-b (SRTXb), and demonstrated toxin-induced phosphoinositide hydrolysis. Here we report on the characteristics of /sup 125/I-SRTXb receptors and their regional distribution in rat brain. /sup 125/I-SRTX receptors in the rat brain bind the toxin rapidly and with high affinity. The binding was not inhibited by ligands of known neurotransmitter receptor and ion channels. /sup 125/I-SRTX receptors have a distinctive regional distribution. The highest densities were observed in the cerebellum, thalamus and hypothalamus (850, 550 and 450 fmol/mg protein, respectively) and the lowest densities in the caudate and cerebral cortex (82 and 62 fmol/mg protein, respectively). Taken together our results suggest that mammalian brains contain a hitherto undetected neuroreceptor that may operate in neurotransmission with a SRTX-like brain peptide, similar to the SRTX homologous vasoconstrictor peptide of the mammalian endothelium endothelin.
The binding and internalization of /sup 125/I-nerve growth factor (NGF) by PC12 pheochromocytoma cells was studied as a function of extracellular potassium concentration. Both surface-bound and internalized fractions of /sup 125/I-NGF associated with the cells under depolarizing conditions (50 mM K+) increased to 144 +/- 28% (average +/- SEM, six different cell preparations) and to 176 +/- 12% (n = 6), respectively, of those observed at 6.0 mM K+. Scatchard-type analysis of the data indicates increased sites for the binding and internalization of iodinated NGF by the cells. Similar enhancement was observed for cells treated with NGF as well. This voltage-dependent phenomenon was reversible, and also observed in the presence of veratridine. Moreover, withdrawal of extracellular Ca2+ abolished high K+-induced modulation of /sup 125/I-NGF binding and internalization, indicating that this effect may be mediated by Ca2+.
[^1^2^5I]YP20: A novel radioligand specific for the extracellular domain of the CRF1 receptor
The peptide corticotropin-releasing factor (CRF) binds to the CRF1 receptor via a two-domain mechanism such that the extracellular domain (ECD) of the receptor captures the CRF's C-terminus to facilitate the binding of CRF's N-terminus to the juxta-membrane or ''J''-site. Known small molecule antagonists bind to the J-site while known CRF1 receptor peptide radioligands bind to both sites. We report here the in vitro binding properties of the first radioligand that binds exclusively to the ECD of the CRF1 receptor. This ligand, which we named [^1^2^5I]Yamada peptide 20 ([^1^2^5I]YP20), is a radiolabeled analog of a synthetic peptide first reported by Yamada et al. (2004). We confirmed its high affinity for the [^1^2^5I]CRF binding site on the hCRF1 receptor and also found it to potently ant...
Effect of high density lipoproteins on permeability of rabbit aorta to low density lipoproteins
A study was made on the effect of high density lipoproteins (HDL) on the permeability of rabbit aorta to low density lipoproteins (LDL) after intravenous administration of human HDL and human (/sup 125/I)LDL to normal and hypercholesterolemic rabbits. Evaluation of radioactivity in plasma and aorta has shown that the administration of a large dose of HDL decreased the aorta permeability rate for (/sup 125/I)LDL on an average by 19% in normal rabbits, and by 45% in rabbits with moderate hypercholesterolemia. A historadiographic study showed that HDL also decreased the vessel wall permeability to (/sup 125/I)LDL in normal and particularly in hypercholesterolemic animals. The suggestion was made that HDL at very high molar concentration can hamper LDL transportation through the intact endothelial layer into the intima due to the ability of HDL to compete with LDL in sites of low affinity on the surface of endothelial cells.
Standardization of ^1^2^5I and ^1^0^9Cd by the photon-photon coincidence method in PTKMR-BATAN
A photon-photon coincidence system was constructed for the standardization of ^1^2^5I and ^1^0^9Cd in PTKMR-BATAN, Indonesia. Two NaI(Tl) detectors of 76mm diameter x 6mm thickness with 0.5mm aluminum window were used, which were positioned approximately symmetrically to the source holder. The electronic chain was almost the same as for a 4@p@b-@c system. The CANBERRA Multiport II multi channel analyzer was used for energy calibration and a Philips type PM3092 oscilloscope for visualization of the pulses. A polyethylene plastic was used as the source substrate for the ^1^2^5I and ^1^0^9Cd samples. The activity of a ^1^2^5I solution was measured by the photon-photon coincidence and the efficiency extrapolation method (Schrader and Walz, 1987), whereas the activity of a ^1^0^9Cd solution was...
Dose to the basal layer of the skin from /sup 125/I skin contamination
The dose rate to the basal layer of the skin from /sup 125/I contamination can be significantly underestimated if the contamination is assumed to remain on the skin, and not penetrate into the skin. The dose to basal cells has been calculated for two assumed distributions of /sup 125/I with depth in skin and for four basal cell layer depths between 40 and 300 ..mu..m. These results give a maximum cell basal cell dose when the /sup 125/I penetration is about twice the basal cell layer depth. This dose may be the limiting dose (as opposed to thyroid dose) in situations where skin contamination can occur. A limit on skin contamination that will ensure the basal cell dose will not exceed 500 mSv.y/sup -1/ is recommended.
The binding of human epidermal growth factor (hEGF), beta-urogastrone, to plasma membranes isolated from rat gastric mucosa was studied to characterize gastric EGF receptors. The binding of ({sup 125}I)hEGF was temperature dependent, reversible, and saturable. A single class of binding sites for EGF with a dissociation constant of 0.42 nM and maximal binding capacity of 42 fmol/mg protein was suggested. There was little change in the binding of ({sup 125}I)hEGF upon addition of peptide hormones (secretin, insulin), antiulcer drugs (cimetidine), or an ulcer-inducing reagent (aspirin). Cross-linking of ({sup 125}I)hEGF to gastric plasma membranes with the use of disuccinimidyl suberate resulted in the labeling of a protein of 150 kDa. These results indicate the presence of EGF receptors on plasma membranes of rat gastric mucosa.
An experimental model of acute pancreatitis in rats has been used to study intrapulmonary /sup 125/I-fibrinogen and /sup 111/In-platelet deposition. Pancreatitis caused a significant increase in wet lung weight compared to normal, and this could be abolished by heparin or aspirin pretreatment. /sup 125/I-fibrinogen was deposited in the lungs of animals to a significantly greater degree than in controls (P less than 0.01). /sup 125/I-fibrinogen deposition was reduced to control levels by pretreatment with aspirin or heparin (P less than 0.05). The uptake of radiolabeled platelets was greater in pancreatitis than in controls (P less than 0.001). Pancreatitis appears to be responsible for platelet entrapment in the lungs. Platelet uptake was reduced by heparin treatment but unaffected by aspirin therapy.
PurposeTo investigate the role of silicone oil as an adjunct to iodine 125 (125I) brachytherapy in attenuating radiation dose and reducing radiation retinopathy.MethodsA 16-mm COMS plaque loaded with 125I seeds was simulated in vitro on an eye model containing silicone oil as a vitreous substitute using BrachyDose. The radiation dose ratio of silicone oil vs water to ocular structures was calculated at angles subtended from the centre of the eye. Silicone oil was then used in three choroidal melanoma patients who underwent 23-gauge vitrectomy, silicone oil placement, and 125I brachytherapy.ResultsSilicone oil reduced the ocular radiation dose in vitro to 65%. Radiation dose ratios on the retina increased from 0.45 to 0.99 when moving from points diametrically opposed to the plaque’s ...
Sensitive radioimmunoassay for detection of antibodies to recombinant human interferon-alpha A
A radioimmunoassay (RIA) for the detection of antibodies to recombinant human leukocyte interferon A (rHuIFN-alpha A) in human serum has been developed and validated against the standard antiviral neutralization bioassay (ANB). The assay measures the binding of /sup 125/I-labeled rHuIFN-alpha A to immunoglobulins in serum. Aliquots of patients' sera are incubated with /sup 125/I-rHuIFN-alpha A and the complexes formed between antibodies in the sera and the /sup 125/I-rHuIFN-alpha A are precipitated with goat anti-human IgG serum. The radioactivity in the immune precipitate is a measure of the quantity of antibody (if present) in the serum. The sensitivity of this RIA is 5 ng of IgG/ml of serum.
Lipofilling in skin affected by radiodermatitis: clinical and ultrasound aspects. Case report.
In recent years, lipofilling has established itself as one of the most effective and least invasive techniques to treat connective dystrophy subsequent to radiotherapy. We report the case of a patient diagnosed with intraductal carcinoma of the right breast in 1996, at the age of 41. The patient underwent quadrantectomy with ipsilateral axillary lymph node dissection and adjuvant chemotherapy and radiotherapy. Four years later, a recurrence led the patient to undergo a subcutaneous mastectomy and immediate reconstruction, involving the submuscular insertion of a permanent implant. In 2007 the patient suffered both radiodermatitis and capsular contracture around the implant, causing constant pain and significant functional limitation. She first took a leukotriene inhibitor (Zafirlukast, 20 mg daily for 8 months) to reduce the capsular contracture. She then underwent lipofilling (Coleman's technique) of the area affected by radiodermatitis, in which the skin was considerably thinned and visibly ischemic. A second session followed four months later. Clinical, photographic and ultrasound examination revealed clear and lasting thickening of the superficial tissues, increased coverage of the implant, and reduced skin discoloration and tension. PMID:22709457
Ultra-nanocrystalline diamond electrodes: optimization towards neural stimulation applications
Diamond is well known to possess many favourable qualities for implantation into living tissue including biocompatibility, biostability, and for some applications hardness. However, conducting diamond has not, to date, been exploited in neural stimulation electrodes due to very low electrochemical double layer capacitance values that have been previously reported. Here we present electrochemical characterization of ultra-nanocrystalline diamond electrodes grown in the presence of nitrogen (N-UNCD) that exhibit charge injection capacity values as high as 163 µC cm-2 indicating that N-UNCD is a viable material for microelectrode fabrication. Furthermore, we show that the maximum charge injection of N-UNCD can be increased by tailoring growth conditions and by subsequent electrochemical activation. For applications requiring yet higher charge injection, we show that N-UNCD electrodes can be readily metalized with platinum or iridium, further increasing charge injection capacity. Using such materials an implantable neural stimulation device fabricated from a single piece of bio-permanent material becomes feasible. This has significant advantages in terms of the physical stability and hermeticity of a long-term bionic implant.
A 65-year-old Japanese woman was admitted to hospital because of palpitations and faintness. She was diagnosed as having sick sinus syndrome and a permanent pacemaker was therefore implanted. Administration of bepridil (200 mg daily) was started for prevention of atrial flutter and fibrillation after PM implantation. On the twenty-fifth day of Bpd therapy, she developed recurrent syncope. ECG showed QT prolongation, torsades de pointes, and sensing failure. Electrical defibrillation (DF) was performed for ventricular fibrillation or ventricular tachycardia. It was presumed that Bpd had caused not only proarrhythmia but also a transient decrease in the amplitude of ventricular activation at the site of the pacing lead, as the sensing level was gradually restored after the drug was ceased and her plasma concentrations of Bpd decreased. It is also believed that DF had caused a sustained increase in pacing threshold because she developed pacing failure after DF and her pacing threshold had not returned to its prior level although the blood levels of Bpd had been below the minimum detectable level. Although it is well known that torsades de pointes occasionally develops in association with Bpd therapy, it is less evident that pacing and sensing failure may develop in association with Bpd therapy. This case report suggests that we should be aware of this possible outcome when employing Bpd and pacemaker implantation as combination therapy.
In cochlear implant surgery an electrode array is permanently implanted to stimulate the auditory nerve and allow deaf people to hear. Current surgical techniques require wide excavation of the mastoid region of the temporal bone and one to three hours time to avoid damage to vital structures. Recently a far less invasive approach has been proposed-percutaneous cochlear access, in which a single hole is drilled from skull surface to the cochlea. The drill path is determined by attaching a fiducial system to the patient's skull and then choosing, on a pre-operative CT, an entry point and a target point. The drill is advanced to the target, the electrodes placed through the hole, and a stimulator implanted at the surface of the skull. The major challenge is the determination of a safe and effective drill path, which with high probability avoids specific vital structures-the facial nerve, the ossicles, and the external ear canal-and arrives at the basal turn of the cochlea. These four features lie within a few millimeters of each other, the drill is one millimeter in diameter, and errors in the determination of the target position are on the order of 0.5mm root-mean square. Thus, path selection is both difficult and critical to the success of the surgery. This paper presents a method for finding optimally safe and effective paths while accounting for target positioning error.
Integrating Remote Follow-Up to Your Clinic Practice
Telemedicine has been made possible by advancements in monitoring technologies. Outpatient clinics are now faced with the challenge of integrating home based monitoring systems with clinic visits in a way that is both efficient and effective for both health provider and patient. Over the past decade, remote follow-up of cardiovascular implantable electronic devices (CIED) has been at the forefront of telemedicine in the US. CIED follow-up includes monitoring the functionality and diagnostic data of implantable cardioverter-defibrillators, cardiac resynchronization devices, permanent pacemakers and implantable loop recorders. Current remote technologies allow full disclosure of programmed and measured data, clinical diagnostic data and automatic checks transmitted via a home monitor to a secure server, accessible to the clinician via computer and/or mobile device. Remote monitoring also allows constant surveillance of lead and battery integrity in CIEDs that have wireless capabilities. The clinic is automatically notified by fax or email when alert thresholds are met. This lecture will discuss lessons learned from our 9 year experience integrating remote CIED follow-up to in-person clinic visits, incorporating recommendations from expert consensus for CIED monitoring.
The patient was a 67-year-old female diagnosed with dilated cardiomyopathy. She had chronic atrial fibrillation (AF) with bradycardia and low left ventricular function (left ventricular ejection fraction (LVEF) 40%). She was admitted for congestive heart failure. She remained New York Heart Association (NYHA) functional class III due to AF bradycardia. Pacemaker implantation was necessary for treatment of heart failure and administration of dose intensive ?-blockers. As she had normal His-Purkinje activation, we examined the optimal pacing sites. Hemodynamics of His-bundle pacing and biventricular pacing were compared. Pulmonary capillary wedge pressure (PCWP) was significantly lower on His-bundle pacing than right ventricular (RV) apical pacing and biventricular pacing (13 mmHg, 19 mmHg, and 19 mmHg, respectively) with an almost equal cardiac index. Based on the examination we implanted a permanent pacemaker for Direct His-bundle pacing (DHBP). After the DHBP implantation, the LVEF immediately improved from 40% to 55%, and BNP level decreased from 422 pg/ml to 42 pg/ml. The number of premature ventricular complex (PVC) was decreased, and non sustained ventricular tachycardia (NSVT) disappeared. Pacing threshold for His-bundle pacing has remained at the same level. His-bundle pacing has been maintained during 27 months and her long-term DHBP can improve cardiac function and the NYHA functional class.
Usefulness of Implantable Loop Recorder in a Patient with Syncope during Bathing
A 27-year-old man was seen in the cardiology department of our hospital because of syncope. Repeated syncope occurred especially during bathing or on a hot day since one year ago. Baseline ECG revealed no abnormality and no organic heart disease was detected by echocardiogram. Holter recording showed no ventricular event or any bradycardia. Tilt test could not induce any bradycardia, however, blood pressure decreased by 39 mmHg (no symptom). Neutrally-mediated syncope (vasoinhibitory type) was mostly suspected at this time. Since no bradycardia/tachycardia including ventricular arrhythmia was induced on electrophysiological study, implantable loop recorder (ILR) was implanted. After 2 months he had syncope when he took a bath at midnight. Though he almost drowned in the bathtub, his family rescued him successfully. In a meanwhile his consciousness recovered completely. He did not have any sequelae at all. Sinus arrest and a maximum ventricular pause of 10.2 seconds were documented with ILR during this syncopal attack. He was treated with a permanent pacemaker implantation. The changes of blood pressure and heart rate during taking bath are quite complicated. While ordinary Holter recording can not be used in a bathroom, ILR can work even in this situation. ILR has much possibility to detect a cause of syncopal attack even in the cases with repeated syncope during bathing.
Paraspinal tumors: Techniques and results of brachytherapy
Because of their proximity to nerve roots and the spinal cord, it is frequently difficult to achieve complete resection of paraspinal tumors. We have used brachytherapy in an attempt to prevent local recurrence and its associated neurological sequelae. This report analyzes our experience with 35 patients to determine the feasibility, optimal techniques, and efficacy of this approach. The tumor types were non small-cell lung cancer (18), sarcomas (9), and other tumor types (8). Temporary, single plane implants using Ir-192 (median minimum peripheral dose 3000 cGy) were used in 21 patients, and permanent I-125 implants were used in 14 cases (median matched peripheral dose 12,500 cGy). Local control was achieved in 51% (18/35). However, local control was poor when lung cancers were implanted and in cases where the dura was exposed. Radiation myelitis did not occur despite the combined effects of previous external beam radiotherapy (N = 21) and brachytherapy. Our experience demonstrates that combined surgery and paraspinal brachytherapy can be performed with acceptable toxicity and is reasonably effective in preventing local relapse and its neurologic sequelae, particularly for tumors other than lung cancers.
Surgeons are commonly confronted with breast contour deformities and defects that result from previous surgical interventions. These soft tissue deformities can be corrected by conventional reconstructive flap surgery using autologous tissue, but there can be donor site morbidity. Smaller volume replacement is possible using temporary fillers such as hyaluronic acid or polylactic acid, or by using 'permanent' fillers such as autologous fat, but large defects are notoriously difficult to fill and often the fillers resorb or migrate. The patient described in this case report had an exchange of polyurethane implant (PU) in the left breast and correction of a contralateral breast contour filling deformity. A left breast partial capsulectomy was performed after implant removal and the capsule graft was inserted into a predissected pocket where soft tissue augmentation was required. A biopsy from the PU capsule was reported to show a foreign body type giant cell reaction to PU material in a fibrous capsule, lined by synovial metaplasia. The post-operative result showed satisfactory soft tissue revolumisation. PU breast implant structured capsule has thus been used as filler to correct breast soft tissue deformity and contour defects. Clearly it may have a use in other anatomical sites. PMID:22503314
Oxygen dependency of epidermal growth factor receptor binding and DNA synthesis of rat hepatocytes
Background/Aims: Changes in oxygen availability modulate replicative responses in several cell types, but the effects on hepatocyte replication remain unclear. We have studied the effects of transient nonlethal hypoxia on epidermal growth factor receptor binding and epidermal growth factor-induced DNA synthesis of rat hepatocytes. Methods: Lactate dehydrogenase activity in culture supernatant, intracellular adenosine triphosphate content, {sup 125}I-epidermal growth factor specific binding, epidermal growth factor receptor protein expression, and {sup 3}H-thymidine incorporation were compared between hepatocytes cultured in hypoxia and normoxia. Results: Hypoxia up to 3 h caused no significant increase in lactate dehydrogenase activity in the culture supernatant, while intracellular adenosine triphosphate content decreased time-dependently and was restored to normoxic levels by reoxygenation (nonlethal hypoxia). Concomitantly, {sup 125}I-epidermal growth factor specific binding to hepatocytes decreased time-dependently (to 54.1% of normoxia) and was restored to control levels by reoxygenation, although {sup 125}I-insulin specific binding was not affected. The decrease in {sup 125}I-epidermal growth factor specific binding was explained by the decrease in the number or available epidermal growth factor receptors (21.37{+-}3.08 to 12.16{+-}1.42 fmol/10{sup 5} cells), while the dissociation constant of the receptor was not affected. The change in the number of available receptors was not considered to be due to receptor degradation-resynthesis, since immuno-detection of the epidermal growth factor receptor revealed that the receptor protein expression did not change during hypoxia and reoxygenation, and since neither actinomycin D nor cycloheximide affected the recovery of {sup 125}I-epidermal growth factor binding by reoxygenation. Inhibition of epidermal growth factor-induced DNA synthesis after hypoxia (to 75.4% of normoxia by 3 h hypoxia) paralleled the decrease in {sup 125}I-epidermal growth factor binding. (au). 27 refs.
Receptor-mediated endocytosis of /sup 125/I-insulin and /sup 125/I-prolactin into liver parenchymal cells has been studied by quantitative subcellular fractionation. Differential centrifugation yielded three particulate fractions, N (nuclear), ML (large granule), and P (microsomes), and a final supernatant (S). Quantitative differences in the extent and rates of accumulation of /sup 125/I-insulin and /sup 125/I-prolactin into the fractions were observed. The acidotropic agent chloroquine and the microtubule disrupting agent colchicine were administered separately to rats. The agents increased significantly the T 1/2 of hormone clearance from the liver and augmented the accumulation of both ligands in the low-speed ML fraction. However, differences in the rates of accumulation of insulin and prolactin into all cell fractions were still maintained. Analytical centrifugation of each of the particulate fractions was carried out in order to determine if different endocytic components were specific to insulin or prolactin internalization. This was not the case. An ''early'' endosomal component of density 1.11 was identified in microsomes. A ''late'' endosome of density 1.10 was identified in the large granule (ML) fraction. Both endosomal components appeared to accumulate insulin and prolactin but at different rates. Marker enzyme analysis identified the presumed plasma membrane component in microsomes (density approximately 1.155). This component showed a significant difference in the rate of loss of /sup 125/I-insulin (T 1/2 approximately 4.1 min) as compared to that of /sup 125/I-prolactin (T 1/2 approximately 12.7 min). A further difference in the handling of the ligands was observed in early endosomes.
In the present study, we have used isolated mouse pancreatic acini were used to investigate the relationship between /sup 125/I-insulin binding and its degradation in order to probe the nature and cellular localization of the degradative process. In these cells, the proteolysis of /sup 125/I-insulin was dependent on time and cell concentration, and was saturated by unlabeled insulin with a Km of 290 nM. Since this value was much higher than the Kd for insulin binding to its receptor (1.1 nM), the data indicated that /sup 125/I-insulin degradation by acini occurred primarily via nonreceptor mechanisms. Several lines of evidence suggested that insulin was being degraded by the neutral thiol protease, insulin degrading enzyme (IDE). First, insulin degradation was inhibited by thiolreacting agents such as N-ethylmaleimide and p-chloromercuribenzoate. Second, the Km for degradation in acini was similar to the reported Km for IDE in other tissues. Third, the enzyme activity had a relative mol wt of approximately 130,000 by gel filtration, a value similar to that reported for purified IDE. Fourth, the degrading activity was removed with a specific antibody to IDE. Other lines of evidence suggested that enzymes located on the cell surface played a role in insulin degradation by acini. First, the nonpenetrating sulfhydryl reacting agent 5,5' dithiobis-2-nitrobenzoic acid blocked /sup 125/I-insulin degradation. Second, a specific antibody to IDE identified the presence of the enzyme on the cell surface. Third, chloroquine, leupeptin and antipain, agents that inhibit lysosomal function, did not influence /sup 125/I-insulin degradation. Fourth, highly purified pancreatic plasma membranes degraded /sup 125/I-insulin.
Binding and degradation of /sup 125/I-insulin by renal glomeruli and tubules isolated from rats
Isolated rat renal glomeruli and tubules were shown to exhibit specific binding of /sup 125/I-insulin and enzymatic degradation of the hormone. Binding to both renal fractions reached a plateau by 1 h at 22/sup 0/C and increased linearly with increasing protein concentrations. Binding was inhibited in both preparations by insulin and its analogues in the order of relative potency: insulin > despentapeptide insulin > proinsulin, but insulin was ten times more potent in inhibiting /sup 125/I-insulin binding to glomeruli than that to tubules, indicating a different affinity of receptors for the hormone in the two renal fractions (about 17 versus 210 ..mu..g unlabelled insulin/1 inhibiting 50% of the /sup 125/I-insulin binding to glomeruli and tubules, respectively). Bound /sup 125/I-insulin dissociated at a faster rate from tubules than from glomeruli; this release was accelerated by unlabelled insulin in both renal fractions, but to a greater extent in glomeruli than in tubules. Two-thirds of the total bound material released from glomeruli was found to be intact insulin as measured by trichloroacetic acid precipitation, whereas only one-third of the material released from tubules was intact. No direct relationship between binding and degradation of /sup 125/I-insulin in these renal fractions could be demonstrated, however, because of the release of proteolytic enzymes into the incubation medium resulting in almost all degradation being extracellular. Although differing in their affinity for /sup 125/I-insulin the high affinity glomerular insulin receptor and the lower affinity tubular insulin receptor have characteristics similar to those of insulin receptors in insulin responsive tissues.
Study of charge transport mechanisms in (125)I-induced DNA damage at various temperatures.
Purpose: Iodine-125 decay induces localized DNA damage by three major mechanisms: (1) Direct damage by the emitted Auger electrons, (2) indirect damage by diffusible free radicals, and (3) charge neutralization of the residual, highly positively charged, tellurium daughter atom by stripping electrons from neighboring residues. The charge neutralization mechanism of (125)I-induced DNA damage is poorly understood. Charge transport along a DNA molecules can occur by either a hopping mechanism initiated by charge injection into DNA and propagated by charge migration through DNA bases along the DNA length, or by a tunneling mechanism in which charge transfers directly from a donor to an acceptor residue. In the first case additional damage in DNA nucleotides can be inflicted by the traveling charge; therefore, it is important to learn if charge hopping plays a role in (125)I-decay-induced DNA damage. In our previous work, we determined that at 193K the charge hopping mechanism was not an appreciable component of the mechanism of (125)I-induced DNA damage. However, the question whether this is also the case at higher temperatures remained open. Methods: In the current study we used a well-known chemical barrier for charge hopping, 8-oxo-7, 8,-dihydroguanine (8-oxo-G), to assess the role of this mechanism in (125)I-decay-induced DNA damage at the following temperatures: 198, 253, 277 and 298 K. Results: We found that varying the temperature had little effect on the distribution of (125)I-induced DNA breaks, as well as on the breaks found at the 8-oxo-G probe both with and without piperidine treatment. Conclusions: We thus conclude that charge transport by the hopping mechanism is not a major factor in (125)I-decay-induced DNA damage at biologically relevant temperatures. PMID:22631602
Proteins labeled with either /sup 3/H by reductive methylation or /sup 125/I by the chloramine-T method were incubated with Xenopus laevis oocytes; the incorporation and acid precipitability of the proteins were then studied. The uptake rates of both specifically incorporated (vitellogenin) and nonspecifically incorporated proteins (bovine serum albumin and X. laevis serum proteins lacking albumin) were not influenced by the method of labeling. However, /sup 125/I-labeled proteins were apparently degraded at rates far exceeding their /sup 3/H-labeled counterparts, based on the generation of acid-soluble radioactivity. Thus, after a 3-hr incubation, 3 to 5 times more /sup 125/I-labeled bovine serum albumin and X. laevis serum proteins lacking albumin were degraded than the corresponding /sup 3/H-labeled proteins (95% compared to 30% and 75% compared to 15%, respectively), whereas after a 24-hr incubation, the degradation of /sup 125/I-labeled vitellogenin was 15 times greater than that of (/sup 3/H)vitellogenin labeled in vivo (60% compared to 4%). Moreover, examination of the relative amounts of /sup 3/H-compared to /sup 125/I-labeled bovine serum albumin deposited into the exogenously derived yolk platelet compartment of the oocyte revealed 7 times more acid-precipitable /sup 3/H-labeled protein, indicating that the observed discrepancies were not due to reincorporation of the /sup 3/H-labeled ligands. Passage of dissolved oocytes previously exposed to /sup 125/I-labeled bovine serum albumin (chloramine-T method) over a column of Bio-Gel P-10 revealed some breakdown of bovine serum albumin to intermediate molecular weight components and the presence of a large amount (approx. = 90%) of labeled low molecular weight compounds, which analysis showed to be 72% free iodine.
The binding of (/sup 125/I)T3 to sites on human placenta plasma membranes was characterized, and the binding site was solubilized after affinity labeling with N-bromoacetyl-(/sup 125/I)T3 (BrAc(/sup 125/I)T3). Two classes of T3-binding sites were detected. One class has a high affinity (K /sub d/ = 2.0nM) and a low capacity (approximately 320 fmol/mg protein); the other has a low affinity (K /sub k/ = 18.5 microM) and a high capacity (approximately 2.2 pmol/mg protein). The binding sites were found to be specific for T3 in that other thyroid hormone analogs (D-T3, rT3, D-T4, and L-T4) were less effective or ineffective in displacing the bound (/sup 125/I)T3. The affinity labeling ligand BrAc(/sup 125/I)T3 was found to specifically label a protein with an apparent mol wt of 65,000, as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The BrAc(/sup 125/I)T3-labeled protein was solubilized with 2 mM 3-(( 3-cholamidopropyl)dimethylammonio)1-propane sulfonate. The apparent mol wt of the labeled protein was between 140,000 and 150,000 by Sephadex-G-200 gel filtration. These data demonstrate that a high affinity binding site specific for T3 is present on plasma membranes from human placenta and that the binding site is a protein, most likely a dimer, with a native mol wt between 140,000 and 150,000.
The cleavage of disulfide bonds in endocytosed macromolecules was investigated using new disulfide containing macromolecular conjugates. A conjugate, in which ({sup 125}I-tyr) was linked to the nondegradable macromolecular carrier poly D-lysine (PDL) through a disulfide spacer ({sup 125}I-tyr-SS-PDL), was used to monitor disulfide cleavage in adsorptive endocytosis in Chinese hamster ovary cells. Reductive cleavage of this probe released 3-thiopropionyl-{sup 125} {sup 125}I-tyramine, measurable as acid soluble radioactivity. In pulse experiments, reductive cleavage of {sup 125}I-tyr-SS-PDL differed in its kinetics from the proteolysis of {sup 125}I-labeled Poly L-lysine. Proteolytic degradation began after a 15 to 30 min lag, i.e. the time required for transport of poly(lysine) to heavy lysosomes, while reductive cleavage increased linearly between 0 and 15 min. In the first hour of chase, proteolytic and reductive cleavage amounted to 30% and 7% of the total cell bound radioactivity, respectively. The reductive cleavage observed during the first 30 min of chase was inhibited by 80-90% with cell impermeant sulfhydryl reagents (dithiobis-(2-nitrobenzoic acid) and p-chloromercuriphenyl-sulfonate), which indicated that cleavage occurred at the cell surface. In contrast, disulfide cleavage observed after 1 hr chase was not significantly inhibited by these reagents and, therefore, resulted from an intracellular process. Subcellular fractionation demonstrated that lysosomes could be excluded as a site of disulfide cleavage, but that a subcellular fraction characterized by a buoyant density of 1.03g/ml was associated with the cleavage of {sup 125}I-tyr-SS-PDL. Of the relevant structures which constitute this subcellular fraction, early endosomes and plasma membrane could be excluded as the reducing structures on the basis of kinetic considerations.
Three radioligands have been commonly used to label putative nicotinic cholinoceptors in the mammalian central nervous system: the agonists (/sup 3/H)nicotine and (/sup 3/H)acetylcholine ((/sup 3/H)ACh--in the presence of atropine to block muscarinic receptors), and the snake venom extract, (/sup 125/I)-alpha-bungarotoxin((/sup 125/I)BTX), which acts as a nicotinic antagonist at the neuromuscular junction. Binding studies employing brain homogenates indicate that the regional distributions of both (/sup 3/H)nicotine and (/sup 3/H)ACh differ from that of (/sup 125/I)BTX. The possible relationship between brain sites bound by (/sup 3/H)nicotine and (/sup 3/H)ACh has not been examined directly. The authors have used the technique of autoradiography to produce detailed maps of (/sup 3/H)nicotine, (/sup 3/H)ACh, and (/sup 125/I)BTX labeling; near-adjacent tissue sections were compared at many levels of the rat brain. The maps of high affinity agonist labeling are strikingly concordant, with highest densities in the interpeduncular nucleus, most thalamic nuclei, superior colliculus, medial habenula, presubiculum, cerebral cortex (layers I and III/IV), and the substantia nigra pars compacta/ventral tegmental area. The pattern of (/sup 125/I)BTX binding is strikingly different, the only notable overlap with agonist binding being the cerebral cortex (layer I) and superior colliculus. (/sup 125/I)BTX binding is also dense in the inferior colliculus, cerebral cortex (layer VI), hypothalamus, and hippocampus, but is virtually absent in thalamus. Various lines of evidence suggest that the high affinity agonist-binding sites in brain correspond to nicotinic cholinergic receptors similar to those found at autonomic ganglia; BTX-binding sites may also serve as receptors for nicotine and are possibly related to neuromuscular nicotinic cholinoceptors.
[[sup 125]I](S)-trans-7-OH-PIPAT: A potential SPECT imaging agent for sigma binding sites
[[sup 125]I](S)-trans-7-hydroxy-2-[N-n-propyl-N-(3[prime]-iodo-2[prime]-propenyl)]aminotetralin ([[sup 125]I](s)-trans-7-OH-PIPAT) has been prepared as an iodinated radioligand for studying the sigma binding site. [[sup 125]I](s)-trans-7-OH-PIPAT binds to rat cerebellar membranes with a K[sub d]=1.67 [+-] 0.07 nM and B[sub max] =240 [+-] 72 fmol/mg of protein (determined in the presence of 15 nM spiperone). This new ligand appears to bind to only one site with Hill coefficients close to unity. Inhibition constants for competing ligands determined in the cerebellar tissue homogenates (in the presence of 15 nM spiperone) are closely comparable to inhibition constants determined in the whole brain tissue homogenates (in the absence of spiperone). Furthermore, these inhibition constants are consistent with the values reported for typical sigma ligands. In vivo uptake of [[sup 125]I](S)-trans-7-OH-PIPAT in the rat brain is initially high (2.52% dose/organ at 2 min post i.v. injection) and displays a rapid washout from the brain (0.8% dose/organ at 30 min post i.v. injection). Uptake of [[sup 125]I](S)-trans-7-OH-PIPAT shows moderate target to non-target ratios of 30 minutes (1.54, 1.66 and 1.92 for cerebellar, hypothalamic and hindbrain uptake over striatal uptake, respectively). Pre-injection with haloperidol reduced these ratios to unity suggesting that the ligand binds specifically to haloperidol-sensitive sites in vivo. The selectivity and affinity of [[sup 125]I](S)-trans-7-OH-PIPAT suggest that this new iodinated ligand may be useful for in vitro studies of the sigma sites and can be used in vivo as a potential SPECT imaging agent.
The diverse inhibitors of bovine heart mitochondrial complex I (NADH-ubiquinone oxidoreductase) are believed to share a common large binding domain with partially overlapping sites, though it remains unclear how these binding sites relate to each other. To obtain new insight into the inhibitor binding domain in complex I, we synthesized a photoreactive azidoquinazoline {[(125)I]-6-azido-4-(4-iodophenethylamino)quinazoline, [(125)I]AzQ}, in which a photolabile azido group was introduced into the toxophoric quinazoline ring to allow specific cross-linking, and carried out a photoaffinity labeling study using bovine heart submitochondrial particles. Analysis of the photo-cross-linked proteins by peptide mass fingerprinting and immunoblotting revealed that [(125)I]AzQ specifically binds to the 49 kDa and ND1 subunits with a frequency of approximately 4:1. The cross-linking was completely blocked by excess amounts of other inhibitors such as acetogenin and fenpyroximate. Considerable cross-linking was also detected in the ADP/ATP carrier and 3-hydroxybutyrate dehydrogenase, though it was not associated with dysfunction of the two proteins. The partial proteolysis of the [(125)I]AzQ-labeled 49 kDa subunit by V8-protease and N-terminal sequencing of the resulting peptides revealed that the amino acid residue cross-linked by [(125)I]AzQ is within the sequence region Thr25-Glu143 (118 amino acids). Furthermore, examination of fragment patterns generated by exhaustive digestion of the [(125)I]AzQ-labeled 49 kDa subunit by V8-protease, lysylendopeptidase, or trypsin strongly suggested that the cross-linked residue is located within the region Asp41-Arg63 (23 amino acids). The present study has revealed, for the first time, the inhibitor binding site in complex I at the sub-subunit level. PMID:19128036
The ND1 subunit constructs the inhibitor binding domain in bovine heart mitochondrial complex I.
The inhibitor binding domain in bovine complex I is believed to be constructed by multisubunits, but it remains to be learned how the binding positions of chemically diverse inhibitors relate to each other. To get insight into the inhibitor binding domain in complex I, we synthesized a photoreactive acetogenin [[125I](trifluoromethyl)phenyldiazirinylacetogenin, [125I]TDA], in which an aryldiazirine group serves as both a photoreactive group and a substitute for the gamma-lactone ring that is a common toxophore of numerous natural acetogenins, and carried out photoaffinity labeling to identify the labeled subunit using bovine heart submitochondrial particles (SMP). When SMP were UV-irradiated in the presence of [125I]TDA, radioactivity was predominantly incorporated into an approximately 30 kDa band on a SDS gel. Blue native gel electrophoresis of the [125I]TDA-labeled SMP revealed that the majority of radioactivity was observed in complex I. Analysis of complex I on a SDS gel showed a predominant peak of radioactivity at approximately 30 kDa. Immnoprecipitation of the [125I]TDA-labeled complex I with anti-bovine ND1 antibody indicated that the labeled protein is the ND1 subunit. A variety of complex I inhibitors such as piericidin A and rotenone efficiently suppressed the specific binding of [125I]TDA to ND1, indicating that they share a common binding domain. However, the suppression efficiency of Deltalac-acetogenin, a new type of complex I inhibitor synthesized in our laboratory, was much lower than that of the traditional inhibitors. Our results unequivocally reveal that the ND1 subunit constructs the inhibitor binding domain, though the contribution of this subunit has been challenged. Further, the present study corroborates our previous proposition that the inhibition site of Deltalac-acetogenins differs from that of traditional inhibitors. PMID:17474759
The effect of the oxystilbene derivative F3 was tested on nAChRs of whole-cell patch-clamped rat chromaffin cells in vitro and of rat adrenal gland membranes using (125)I-epibatidine. F3 (30 nM) rapidly and reversibly blocked inward currents generated by pulse applications of nicotine, shifting the dose-response curve to the right in a parallel fashion without changing the maximum response. The action of F3 was voltage insensitive and not due to altered current reversal potential. The R isomer of F3 was more potent (IC(50) = 350+/-30 nM) than its S-enantiomer (IC(50) = 1.5+/-0.3 microM). Nicotine-evoked currents were insensitive to 10 microM alpha-bungarotoxin. Equi-amplitude currents evoked by nicotine or epibatidine were similarly antagonized by R-F3 in a reversible fashion. Epibatidine-evoked currents readily produced receptor desensitization. Adrenal membranes specifically bound (125)I-epibatidine with a single population of binding sites endowed with high affinity (K(D) = 159 pM) and B(max) of 6.5+/-1.3 fmol mg(-1) of protein. (125)I-epibatidine binding was specifically displaced by cytisine (K(i) = 68 nM) or ACh (K(i) = 348 nM). F3 specifically displaced (125)I-epibatidine binding although with lower affinity (K(i) = 29.6 microM) than in electrophysiological experiments. (125)I-epibatidine binding to rat adrenal tissue was insensitive to alpha-bungarotoxin which readily antagonized (125)I-epibatidine binding to bovine adrenal tissue. The present results suggest that F3 is a relatively potent and apparently competitive antagonist of nAChRs on rat chromaffin cells. Since previous studies have indicated that F3 targets different subtypes on chick neuronal tissue, it appears that nAChRs display interspecies differences to be considered for drug development studies. PMID:10780985
Cholecystokinin receptors on gallbladder muscle and pancreatic acinar cells: a comparative study
To compare receptors for cholecystokinin (CCK) in pancreas and gallbladder, we measured binding of 125I-Bolton-Hunter-labeled CCK-8 (125I-BH-CCK-8) to tissue sections from guinea pig gallbladder and pancreas under identical conditions. In both tissues, binding had similar time-, temperature-, and pH dependence, was reversible, saturable and inhibited only by CCK related peptides or CCK receptor antagonists. Autoradiography localized 125I-BH-CCK-8 binding to the smooth muscle layer in the gallbladder. Binding of 125I-BH-CCK-8 to gallbladder sections was inhibited by various agonists with the following potencies (IC50):CCK-8 (0.4 nM) greater than des(SO3)CCK-8 (0.07 microM) greater than gastrin-17-I (1.7 +/- 0.3 microM) and by various receptor antagonists with the following potencies: L364,718 (1.5 nM) greater than CR 1409 (0.19 microM) greater than asperlicin = CBZ-CCK-(27-32)-NH2 (1 microM) greater than Bt2cGMP (120 microM). Similar potencies were found for the agonists and antagonists for pancreas sections. Inhibition of binding of 125I-BH-CCK-8 by 11 different analogues of proglumide gave similar potencies for both pancreas and gallbladder. The potencies of agonists in stimulating and antagonists in inhibiting CCK-stimulated contraction or amylase release correlated closely with their abilities to inhibit 125I-BH-CCK-8 binding to gallbladder or pancreas sections or acini, respectively. The present results demonstrate and characterize a method that can be used to compare the CCK receptors in guinea pig gallbladder and pancreas under identical conditions. Moreover, this study demonstrates that gallbladder and pancreatic CCK receptors have similar affinities for the various agonists and antagonists tested and, therefore, provides no evidence that they represent different subtypes of CCK receptors that can be distinguished pharmacologically.
Kinetics of binding of cholecystokinin to pancreatic acini
In the present study the authors examined the kinetics of binding of iodinated COOH-terminal octapeptide of cholecystokinin ({sup 125}I-CCK-8) to its receptors on dispersed acini prepared from guinea pig pancreas. At 37{degree}C, binding of {sup 125}I-CCK-8 reached a steady state after 60 min of incubation. Dissociation of bound {sup 125}I-CCK-8 was biphasic, indicating that the labeled peptide binds in two distinct states: a rapidly dissociating state and a slowly dissociating state. Binding of {sup 125}I-CCK-8 in the rapidly dissociating state was maximal within 3 min of incubation, did not depend on incubation temperature or cellular energy metabolism, could be stripped by 0.5 M potassium thiocyanate, and showed accelerated dissociation with CCK-8 or dibutyrylguanosine 3{prime},5{prime}-cyclic monophosphate (Bt{sub 2}cGMP). Binding of {sup 125}I-CCK-8 in the slowly dissociating state was maximal after 60 min of incubation, was decreased by reducing the incubation temperature or inhibiting cellular energy metabolism, was not stripped by 0.5 M potassium thiocyanate, and did not show accelerated dissociation with CCK-8 or Bt{sub 2}cGMP. Computer analysis of the inhibition of {sup 125}I-CCK-8 by CCK-8 under experimental conditions where the rapidly dissociating state predominates demonstrated a complete loss of high-affinity binding sites. The present results demonstrate that labeled CCK-8 can bind in two kinetic states that have not been incorporated into previous models of CCK-receptor interaction based on stoichiometric studies.
/sup 125/I-neuropeptide Y and /sup 125/I-peptide YY bind to multiple receptor sites in rat brain
We describe the preparation of monoiodinated neuropeptide Y (Tyr1-125I-NPY) and monoiodinated peptide YY (Tyr36-125I-PYY). Using these ligands, we detected high, moderate, and low affinity receptor populations in rat brain. Only high and moderate affinity binding sites were suggested by saturation binding studies. Tyr1-125I-NPY bound to 8 +/- 3% of the sites with a Kd of 54 pM (Bmax = 19.4 fmol/mg of protein) and to 92 +/- 3% of the sites with a Kd of 0.92 nM (Bmax = 220.0 fmol/mg of protein). Tyr36-125I-PYY bound to 14 +/- 3% of the sites with a Kd of 23.5 pM (Bmax = 36.4 fmol/mg of protein) and to 86 +/- 3% of the sites with a Kd of 1.9 nM (Bmax = 220.1 fmol/mg of protein). The fragments NPY 13-36 and PYY 13-36 were able to compete with 10 pM Tyr1-125I-NPY for essentially all the binding sites. The fragments were 1 to 2 orders of magnitude less potent than the native peptides. Approximately 50% of the moderate affinity sites, but not the high affinity sites, were reversibly lost in the presence of 5'-guanylyl imidophosphate (Gpp(NH)p), a nonhydrolyzable analog of GTP. Kinetic studies revealed that Tyr1-125I-NPY dissociation could be best described by three dissociation rates. The proportions of slow and intermediate dissociation matched the proportions of moderate and high affinity binding sites, respectively, as suggested by equilibrium studies. There also existed a phase of fast dissociation. When Gpp(NH)p was added during dissociation, the proportion of slow dissociation decreased to the same extent that the fast dissociation was increased. However, the proportion of intermediate dissociation did not change. We propose that rat brain contains a minor population of high affinity NPY binding sites with an intermediate dissociation rate and no sensitivity to Gpp(NH)p.
Thyroid function in post-weaning rats whose dams were fed a low-protein diet during suckling
Abstract in english This study was designed to evaluate the thyroid and pituitary hormone levels in post-weaning rats whose dams were fed a low-protein diet during suckling (21 days). The dams and pups were divided into 2 groups: a control group fed a diet containing 22% protein that supplies the necessary amount of protein for the rat and is the usual content of protein in most commercial rat chow, and a diet group fed a low-protein (8%) diet in which the protein was substituted by an isoca (more) loric amount of starch. After weaning all dams and pups received the 22% protein diet. Two hours before sacrifice of pups aged 21, 30 and 60 days, a tracer dose (0.6 µCi) of 125I was injected (ip) into each animal. Blood and thyroid glands of pups were collected for the determination of serum T4, T3 and TSH and radioiodine uptake. Low protein diet caused a slight decrease in radioiodine uptake at 21 days, and a significant decrease in T3 levels (128 ± 14 vs 74 ± 9 ng/dl, P<0.05), while T4 levels did not change and TSH was increased slightly. At 30 days, T3 and TSH did not change while there was a significant increase in both T4 levels (4.8 ± 0.3 vs 6.1 ± 0.2 µg/dl, P<0.05) and in radioiodine uptake levels (0.34 ± 0.02 vs 0.50 ± 0.03%/mg thyroid, P<0.05). At 60 days serum T3, T4 and TSH levels were normal, but radioiodine uptake was still significantly increased (0.33 ± 0.02 vs 0.41 ± 0.03%/mg thyroid, P<0.05). Thus, it seems that protein malnutrition of the dams during suckling causes hypothyroidism in the pups at 21 days that has a compensatory mechanism increasing thyroid function after refeeding with a 22% protein diet. The radioiodine uptake still remained altered at 60 days, when all the hormonal serum levels returned to the normal values, suggesting a permanent change in the thyroid function
Imaging the adrenal medulla with an I-131-labeled antiadrenergic agent. [Bretylium analogs
Tissue distributions of four antiadrenergic agents labeled with iodine-125 have been determined in dogs. (/sup 125/I) ortho-iodobenzyldimethyl-2-hydroxyethyl ammonium and (/sup 125/I) ortho-iodobenzyldimethylethyl ammonium show highly selective uptake in the adrenal medulla. Studies of molecular structure-distribution indicate that both the nature of the cationic head and the ring position of theiodine atom greatly influence adrenal specificity. Distinct images of dogs' adrenal medulla have been obtained 4 days after i.v. injection of 1.5 mCi of (/sup 131/I) ortho-iodobenzyldimethyl-2-hydroxyethyl ammonium.
p-( sup 125 I)iodoclonidine is a partial agonist at the alpha 2-adrenergic receptor
The binding properties of p-(125I)iodoclonidine (( 125I)PIC) to human platelet membranes and the functional characteristics of PIC are reported. (125I)PIC bound rapidly and reversibly to platelet membranes, with a first-order association rate constant (kon) at room temperature of 8.0 +/- 2.7 x 10(6) M-1 sec-1 and a dissociation rate constant (koff) of 2.0 +/- 0.8 x 10(-3) sec-1. Scatchard plots of specific (125I)PIC binding (0.1-5 nM) were linear, with a Kd of 1.2 +/- 0.1 nM. (125I)PIC bound to the same number of high affinity sites as the alpha 2-adrenergic receptor (alpha 2-AR) full agonist (3H) bromoxidine (UK14,304), which represented approximately 40% of the sites bound by the antagonist (3H)yohimbine. Guanosine 5'-(beta, gamma-imido)triphosphate greatly reduced the amount of (125I)PIC bound (greater than 80%), without changing the Kd of the residual binding. In competition experiments, the alpha 2-AR-selective ligands yohimbine, bromoxidine, oxymetazoline, clonidine, p-aminoclonidine, (-)-epinephrine, and idazoxan all had Ki values in the low nanomolar range, whereas prazosin, propranolol, and serotonin yielded Ki values in the micromolar range. Epinephrine competition for (125I)PIC binding was stereoselective. Competition for (3H)bromoxidine binding by PIC gave a Ki of 1.0 nM (nH = 1.0), whereas competition for (3H)yohimbine could be resolved into high and low affinity components, with Ki values of 3.7 and 84 nM, respectively. PIC had minimal agonist activity in inhibiting adenylate cyclase in platelet membranes, but it potentiated platelet aggregation induced by ADP with an EC50 of 1.5 microM. PIC also inhibited epinephrine-induced aggregation, with an IC50 of 5.1 microM. Thus, PIC behaves as a partial agonist in a human platelet aggregation assay. (125I)PIC binds to the alpha 2B-AR in NG-10815 cell membranes with a Kd of 0.5 +/- 0.1 nM.
Research in nuclear physics: Progress report, June 1, 1993--July 31, 1994
The main emphasis of the program are studies of the structure of neutron-rich nuclei and rare electron capture processes. Research topics discussed are: (1) search for a 17 keV neutrino in internal bremsstrahlung spectrum of {sup 125}I; (2) absolute intensity of internal bremsstrahlung for the EC decay of {sup 125}I; (3) internal bremsstrahlung endpoint of {sup 109}Cd; (4) search for massive neutrinos in the recoil spectrum of {sup 37}Cl following electron capture decay of {sup 37}Ar; (5) the Auger relaxation of {sup 37}Cl following electron capture decay of {sup 37}Ar; and (6) neutralization of ions after neutrino-induced desorption;
An in vitro autoradiographic assay was used in identifying a magnesium-dependent, non-specific binding of (/sup 125/I) prolactin to myelinated fiber tracts in the rat brain. Frozen tissue sections were incubated for 18 h at 4 degrees C in media which included (/sup 125/I)prolactin alone or with a 500 fold excess of unlabelled prolactin. Magnesium in the incubation medium caused a non-specific binding of radiolabelled prolactin to the myelinated fiber tracts in the brain. In contrast, calcium did not facilitate prolactin non-specific binding to myelin. Hence, calcium should optimize the detection of specific prolactin binding sites in the brain by in vitro autoradiographic or radioreceptor assays.
The moxestrol analog 17..cap alpha..-(/sup 125/I)iodovinyl-11..beta..-methoxyestradiol was prepared in 95% radiochemical yield from the corresponding 17..cap alpha..-(tributylstannyl)vinyl compound and no-carrier-added sodium (/sup 125/I)iodide. The new radioligand was evaluated in immature female rats to determine the uptake in and selectivity for tissues containing estrogen receptors. At 1, 2, and 6 hr after injection, the agent demonstrates both high selectivity (uterus to blood ratio) and a high concentration in the largest tissue. The compounds's biologic properties and its ease of preparation suggest that it would be a likely candidate for clinical use as an estrogen-receptor-seeking radiopharmaceutical.
External imaging of human atherosclerosis
Autologous plasma low-density lipoproteins labeled with /sup 125/I were used as a tracer to identify atherosclerotic lesions in the carotid arteries of the neck. Following intravenous injection of /sup 125/I-LDL, images were made at intervals from 6 to 36 hr with the gamma camera in three patients with known carotid disease and one control subject. The carotid lesions, confirmed by angiography, were imaged successfully in all three patients, whereas no focal LDL accumulation was visible in the carotid arteries of the control subject. The findings suggest that it may be possible to image atherosclerosis externally and thus to follow the course of the disease.
Specific dot-immunobinding assay for detection and enumeration of Thiobacillus ferrooxidans
A specific and very sensitive dot-immunobinding assay for the detection and enumeration of the bioleaching microorganism Thiobacillus ferrooxidans was developed. Nitrocellulose spotted with samples was incubated with polyclonal antisera against whole T. ferrooxidans cells and then in {sup 125}I-labeled protein A or {sup 125}I-labeled goat antirabbit immunoglobulin G; incubation was followed by autoradiography. Since a minimum of 10{sup 3} cells per dot could be detected, the method offers the possibility of simultaneous processing of numerous samples in a short time to monitor the levels of T. ferrooxidans in bioleaching operations.
Stable high capacity, F-actin affinity column
A high capacity F-actin affinity matrix is constructed by binding fluorescyl-actin to rabbit anti-fluorescein IgG that is covalently bound to Sepharose 4B. When stabilized with phalloidin, the actin remains associated with the Sepharose beads during repeated washes, activates the ATPase activity of myosin subfragment 1, and specifically binds /sup 125/I-heavy meromyosin and /sup 125/I-tropomyosin. The associations between the F-actin-binding proteins are monitored both by affinity chromatography and by a rapid, low speed sedimentation assay. Anti-fluorescein IgG-Sepharose should be generally useful as a matrix for the immobilization of proteins containing accessible, covalently bound fluorescein groups.
Specific binding sites for human pancreatic secretory trypsin inhibitor (PSTI) on 3T3 Swiss albino cells were studied using radioiodinated recombinant PSTI. Some ion species, pH, and temperature significantly influenced the binding of 125I-PSTI. Kinetic studies showed that the binding of 125I-PSTI to 3T3 Swiss albino cells reached the maximum level within 120 min at 4 degrees C, with a slow dissociation rate. The half-maximal inhibition (ID50) of 125I-PSTI binding by unlabeled PSTI occurred at 1.0 x 10(-10) M. On Scatchard analysis of the competitive binding data, linear plots indicated a single class of receptors with high affinity (Kd = 5.3 x 10(-10) M) on 3T3 Swiss albino cells, the number of receptors being 5,400 per cell. Treatment of surface-bound radiolabeled PSTI with a chemical crosslinker (disuccinimidyl suberate) led to the identification of a membrane polypeptide of Mr 140,000 to which PSTI was crosslinked. The formation was inhibited by an excess amount of unlabeled PSTI in a dose-dependent manner. The binding of 125I-PSTI to 3T3 Swiss albino cells was competitively inhibited by unlabeled PSTI but not by other peptide hormones, such as epidermal growth factor (EGF), bovine fibroblast growth factor, insulin-like growth factor, transforming growth factor alpha, platelet-derived growth factor, and tumor necrosis factor, indicating the presence of receptors specific for PSTI. Various protease inhibitors had no or only a little effect, and mercaptoethanol and dithiothreitol strongly decreased the binding of 125I-PSTI. Incubation at 37 degrees C resulted in rapid internalization of cell-bound 125I-PSTI, followed by the appearance of trichloroacetic acid-soluble 125I-radioactivity in the culture medium, due to degradation of internalized PSTI. In addition, PSTI stimulated [3H]thymidine incorporation into DNA on 3T3 Swiss albino cells in a dose-dependent manner. The combined addition of PSTI and EGF stimulated [3H]thymidine incorporation to an extent greater than that seen with either agent alone. These results indicated that the biological effect of PSTI was mediated by high affinity plasma membrane receptors, which were not a cell-surface proteinase(s). Specific binding of 125I-PSTI was noted with the following cells: WI-38, 3T3 Swiss albino, HUVE, BDC-1, and H4-II-E-C3. PMID:2170560
Synthesis of [sup 123]I- and [sup 125]I-labelled 5-iodo-6-nitroquipazine
The syntheses of the potent and selective serotonin reuptake complex radioligands [[sup 123]I]- and [[sup 125]I]5-iodo-6-nitroquipazine (5-iodo-6-nitro-2-piperazinylquinoline) are reported. A seven step synthetic sequence provided the BOC-protected 5-tributyltin-6-nitroquipazine precursor for radioiodination. End of sy nthesis radioiodination yields of [approx] 40% for [sup 123]I and [approx] 60% for [sup 125]I were achieved resulting in labelled products with high specific activities (> 4000 and > 2000 Ci/mmol, respectively) and radiochemical purities (> 98%). (author).
As a part of our efforts to develop a meta-iodobenzylguanidine (MIBG) analogue with improved characteristics for the diagnosis and treatment of neuroendocrine tumours, 3-[{sup 131}I]iodo-4-methyl-benzylguanidine ([{sup 131}I]MeIBG) has been developed. The purpose of this study was to evaluate [{sup 131}I]MeIBG in vitro using the uptake-1 positive SK-N-SH neuroblastoma cell line and in vivo in normal mice and mice bearing human neuroblastoma xenografts. The ability of SK-N-SH human neuroblastoma cells to retain [{sup 131}I]MeIBG in vitro over a period of 4 days, in comparison to [{sup 125}I]MIBG, was determined by a paired-label assay. Paired-label biodistributions of [{sup 131}I]MeIBG and [{sup 125}I]MIBG were performed in normal mice as well as in athymic mice bearing SK-N-SH and IMR-32 human neuroblastoma xenografts. Retention of [{sup 131}I]MeIBG by SK-N-SH cells in vitro was increased by factors of 1.2, 1.5, 2.0, 2.5 and 3.1 compared with [{sup 125}I]MIBG at 8, 24, 48, 72 and 96 h, respectively. In normal mice, the uptake of [{sup 131}I]MeIBG in the heart was similar to that of [{sup 125}I]MIBG at 1 and 4 h; in contrast, myocardial uptake of [{sup 131}I]MeIBG was 1.6-fold higher than that of [{sup 125}I]MIBG (p<0.05) at 24 h. When mice were pre-treated with the uptake-1 inhibitor desipramine (DMI), the heart uptake of both tracers was reduced to about half that in untreated controls at 1 h post injection (p<0.05). The hepatic uptake of [{sup 131}I]MeIBG was two- to threefold lower than that of [{sup 125}I]MIBG. On the other hand, blood levels of [{sup 131}I]MeIBG were substantially higher (up to sixfold), especially at early time points. Uptake of [{sup 131}I]MeIBG in heart and tumour at 1 h in the murine SK-N-SH model was specific and comparable to that of [{sup 125}I]MIBG. However, [{sup 131}I]MeIBG uptake was 1.6- to 1.7-fold lower than that of [{sup 125}I]MIBG over 4-48 h. While the uptake of both tracers in IMR32 xenografts was similar, it was not uptake-1 mediated. Introduction of a methyl group at the 4-position of MIBG seems to be advantageous in terms of higher tumour retention in vitro and lower hepatic uptake in vivo. However, the slower blood clearance of MeIBG may be problematic for some applications. (orig.)
What's known on the subject? and What does the study add? While the frequencies and severity of late toxicities following prostate brachytherapy are well known, less has been published with regard to time to first onset. Several series with limited median follow-up have published time to onset. An extensive analysis of timing to late toxicity following brachytherapy for cervical cancer has also been published. This study is the largest of its kind with the longest median follow-up to capture very late events. It can provide a basis for physician and patient education about when late toxicities can reasonably be expected to occur. The study also shows that a significant amount of erectile dysfunction might be more age related than radiation induced. OBJECTIVES: •? To assess the timing of first onset of late rectal bleeding, late haematuria and erectile dysfunction (ED) following brachytherapy with or without external beam radiation therapy (EBRT) for prostate adenocarcinoma. •? To identify treatment factors and patient characteristics that affect the time to first onset. PATIENTS AND METHODS: •? In all, 2046 patients were definitively treated for prostate adenocarcinoma with a full (125) I or (103) Pd implant or a partial (103) Pd implant followed by EBRT with 6 years median follow-up (range 2-17 years). •? Patients were selected for an event of Radiation Therapy Oncology Group (RTOG) grade 2 or greater rectal bleeding, ?RTOG grade 2 haematuria, or a drop in the Mount Sinai Erectile Dysfunction Score from potent to impotent (excluding patients who received androgen deprivation therapy). •? Life tables were generated to calculate actuarial incidence rates of toxicity. •? Wilcoxon rank sum and Cox regression were utilized to identify treatment factors affecting time to onset. RESULTS: •? The incidence rate per 1000 patients for 0-2 years, 2-5 years and 5-10 years following radiation for rectal bleeding is 14.3, 15.9 and 6.5, respectively; for haematuria, 14.0, 8.2 and 1.3, respectively; and for ED, 82.4, 48.2 and 42.2, respectively. •? Just 5% of rectal bleeding occurs after 5 years from radiation vs 18% of haematuria cases and 22% of ED. •? On multivariate analysis, time to first onset of rectal bleeding was affected by the addition of EBRT only whereas the time to onset of haematuria was affected by the biological effective dose of the radiation and the addition of EBRT. •? The only factor on multivariate analysis to affect time to onset of ED was the age of the patient at treatment, independent of radiation dose or technique. CONCLUSIONS: •? Unique temporality to first onset of selected toxicities was observed in patients after radioactive implant for prostate adenocarcinoma with or without EBRT. •? Clinicians and patients should be counselled when to expect late toxicities. •? The only factor to affect time to onset of ED is the age of the patient, suggesting possible over-reporting of radiation-induced ED in the light of normal age-related events. PMID:23046084
Interstitial curietherapy in the conservative treatment of anal and rectal cancers
Conservative treatment has become a valid alternative to radical surgery in most cases of cancer of the anal canal and in selected cases of cancer of the low rectum. In this strategy interstitial curietherapy has an appreciable role to play. The results of a series of 369 patients followed more than 3 years indicate that implantation of Iridium-192 is effective not as sole treatment but as a booster dose 2 months after a course of external beam or intracavitary irradiation. The dose delivered did not exceed 20 to 30 Gy and the implantations were always performed in one plane using either a plastic template or a steel fork. Three groups of cases must be considered: (a) among 221 patients with epidermoid carcinoma of the anal canal, the rate of death related to treatment failures was 20% and among the patients cured more than 90% retained normal sphincter function. (b) In 90 patients with T1-T2 invasive adenocarcinoma of the rectum, Iridium-192 was carried out after four applications of contact X ray therapy. The rate of control was 84%. (c) In 62 elderly, poor risk patients with T2-T3 tumor of the low rectum initially suitable for an abdomino-perineal resection, a tentative extension of the field of conservation was made using a split-course protocol combining a short course of external beam irradiation at a dose of 30-35 Gy in 10 fractions over 12 days and an Iridium-192 implant. The rate of death due to treatment failures was 14.5% and among the patients controlled 97% had a normal anal function. These results show that implantations of Iridium-192 may contribute to the control of anal and rectal cancers and may spare many patients a permanent colostomy, but the treatment requires great care in patient selection, treatment protocol, technical details, and follow-up. This treatment policy must be conceived as a team work of radiation oncologists and surgeons.
Transverse Tripolar Spinal Cord Stimulation: Results of an International Multicenter Study.
Experienced neurosurgeons at eight spinal cord stimulation centers in the United States, Canada, and Europe participated in a study from 1997 to 2000 investigating the safety, performance, and efficacy of a Transverse Tripolar Stimulation (TTS) system invented at the University of Twente, the Netherlands. This device was proposed to improve the ability of spinal cord stimulation to adequately overlap paresthesia to perceived areas of pain. Fifty-six patients with chronic, intractable neuropathic pain of the trunk and/or limbs more than three months' duration (average 105 months) were enrolled with follow-up periods at 4, 12, 26, and 52 weeks. All patients had a new paddle-type lead implanted with four electrodes, three of them aligned in a row perpendicular to the cord. Fifteen of these patients did not undergo permanent implantation. Of the 41 patients internalized, 20 patients chose conventional programming using an implanted pulse generator to drive four electrodes, while 21 patients chose a tripole stimulation system, which used radiofrequency power and signal transmission and an implanted dual-channel receiver to drive three electrodes using simultaneous pulses of independently variable amplitude. On average, the visual analog scale scores dropped more for patients with TTS systems (32%) than for conventional polarity systems (16%). Conventional polarity systems were using higher frequencies on average, while usage range was similar. Most impressive was the well-controlled "steering" of the paresthesias according to the dermatomal topography of the dorsal columns when using the TTS-balanced pulse driver. The most common complication was lead migration. While the transverse stimulation system produced acceptable outcomes for overall pain relief, an analysis of individual pain patterns suggests that it behaves like spinal cord stimulation in general with the best control of extremity neuropathic pain. This transverse tripole lead and driving system introduced the concept of electrical field steering by selective recruitment of axonal nerve fiber tracts in the dorsal columns. PMID:22151707
Development and preclinical evaluation of a biodegradable ventricular septal defect occluder.
OBJECTIVES: This study evaluated the feasibility, effectiveness, and safety of a biodegradable (BD) occluder for closure of ventricular septal defect (VSD) in an acute canine model. BACKGROUND: All current available VSD occluders are permanent implants which consist of a metal framework and synthetic fabrics. However, the septal occluder in vivo plays the role of a temporary bridge that facilitates the ingrowth of fibrous connective tissue and endothelialization. The ideal occluder may be a temporary scaffold which can be gradually absorbed in vivo and replaced by "native" tissue. METHODS: The BD VSD occluder consists of a polydioxanone (PDO) framework and two pieces of poly-L-lactic acid (PLLA) fabrics. Percutaneous transcatheter closure of interventionally created VSDs was performed in 16 dogs using the BD occluders. Follow-up consisted of electrocardiography, transthoracic echocardiography, and fluoroscopy from 1 week to 24 weeks post-implantation. Gross pathology and histopathology were obtained at 6, 12, and 24 weeks follow-up. RESULTS: Implantation of the BD occluders was successful in 15 animals. The devices became well integrated into the ventricular septum with complete endothelialization at 12 weeks after implantation. After 24 weeks in vivo, the PDO framework of devices was largely absorbed and replaced by the ingrowth of collagenous fibers, and the PLLA fabric within disks was partly degraded. Neither occluder dislocation nor VSD recanalization occurred during follow-up. CONCLUSIONS: The BD occluder proved safe and effective for VSD closure. This device is characterized by compatible mechanical properties, a fully BD property, and a good match between the degradation of occluder and the healing response of organism. © 2012 Wiley Periodicals, Inc. PMID:22888016
Attachment of an aminoglycoside, amikacin, to implantable collagen for local delivery in wounds.
Cultured skin substitutes consisting of implantable collagen (COL) and cultured human skin cells often fail clinically from destruction by microbial contamination. Hypothetically, addition of selected antimicrobial drugs to the implant may control microbial contamination and increase healing of skin wounds with these materials. As a model for drug delivery, bovine skin COL (1 mg/ml) and amikacin (AM; 46 micrograms/ml) were modified by covalent addition of biotin (B-COL and B-AM, respectively) from B-N-hydroxysuccinimide and bound together noncovalently with avidin (A). B-COL was incubated with A and then with B-peroxidase (B-P) or by serial incubation with B-AM and B-P, before P-dependent chromogen formation. Colorimetric data (n = 12 per condition) from spot tests on nitrocellulose paper were collected by transmission spectrophotometry. Specificity of drug binding in spot tests was determined by (i) serial dilution of B-COL; (ii) reactions with COL, AM, or P that had no B; (iii) removal of A; or (iv) preincubation of B-COL-A with B before incubation with B-P. Binding of B-AM was (i) dependent on the concentration of B-COL; (ii) specific to B-COL, A, and B-P (P < 0.05); and (iii) not eluted by incubation in 0.15 or 1.0 M NaCl. B-AM was found to block binding of B-P to the B-COL-A complex and to retain bacteriocidal activity against 10 clinical isolates of wound bacteria in the wet disc assay. Antimicrobial activity of B-AM was removed from solution by treatment with magnetic A and a permanent magnet. These results suggest that selected antimicrobial drugs can be biotinylated for attachments to COL-cultured cell implants without loss of pharmacologic activity. Because this chemistry utilizes a common ligand, any molar ratio of agents may be administered simultaneously and localized to the site of implantation. PMID:8239602
The use of stem and progenitor cells in cardiovascular therapy has been proposed as a feasible option to promote repair of tissue damage by ischemia, or to devise definitive artificial tissue replacements (valves, vessels, myocardium) to be surgically implanted in patients. Whereas in other medical branches such as dermatology and ophthalmology the use of ex vivo grown tissues is already accessible to a large degree, the use of bio-artificial implants in cardiovascular surgery is still marginal. This represents a major limitation in cardiovascular medicine at present. In fact, the limited durability and the lack of full compatibility of current implantable devices or tissues prevent a long-term resolution of symptoms and often require re-intervention thereby further increasing the economic burden of the cardiovascular disease. Stem cell technology can be of help to derive tissues with improved physiologic function and permanent durability. Specifically, the intrinsic ability of stem cells to produce tissue-specific "niches", where immature cells are perpetuated while differentiated progenitors are continuously produced, makes them an ideal resource for bioengineering approaches. Furthermore, recent advancements in biocompatible material science, designing of complex artificial scaffolds and generation of animal or human-derived natural substrates have made it feasible to have ex vivo reproduction of complex cell environment interactions - a process necessary to improve stem cells biological activity. This review focuses on current understanding of cardiovascular stem cell biology as well as tissue engineering and explores their interdisciplinary approach. By reviewing the relevant recent patents which have enabled this field to advance, it concentrates on various design substrates and scaffolds that grow stem cells in order to materialize the production of cardiovascular implants with enhanced functional and self-renewal characteristics. PMID:22280334
Surface integrity of biodegradable Magnesium-Calcium orthopedic implant by burnishing.
Magnesium-Calcium (MgCa) alloy as an emerging biodegradable implant material has received considerable attention in orthopedic fixation applications. The biodegradable MgCa alloys avoid stress shielding and secondary surgery inherent with permanent metallic implant materials. They also provide sufficient mechanical strength in load carrying applications as opposed to biopolymers. However, the key issue facing a biodegradable MgCa implant is the fast corrosion in the human body environment. The ability to adjust the degradation rate of MgCa alloys is critical in the successful development of biodegradable orthopedic materials. Burnishing as a low plastic deformation process is a promising technique to tune surface integrity of MgCa implant surface for biodegradation control. However, the poor ductility of MgCa alloys imposes a great challenge for burnishing. This study focuses on the basic understanding of surface mechanical behavior of burnished biodegradable MgCa0.8 (wt%) alloy. The effects of burnishing parameters, i.e., pressure, feed, speed, number of path, and burnishing pattern on surface integrity factors such as surface topography, roughness, microhardness, microstructure, and residual stresses are investigated. The burnished surfaces are shinier and smoother than the as-machined ones. The MgCa alloy can be safely burnished at suitable burnishing conditions since no cracks are produced at the surface and in the subsurface. The microstructure including grain size does not show a noticeable change after burnishing. The machined surfaces are harder than the burnished ones down to the deep subsurface (?200 ?m) as opposed to the shallow hardened depth (?50 ?m) in cutting. Residual stresses are highly compressive especially at low burnishing pressure. PMID:22098888
Background: To quantify the effect of implanted low-dose-rate iodine seeds combined with fractionated external beam radiation on local control rates in an experimental tumor system. Materials and Methods: Experiments were done on the rhabdomyosarcoma R1H of the rat transplanted s. c. into the back of male WAG/Raj albino rats. Tumors were irradiated with 200 kVp X-rays with 2 Gy/fraction 5 times weekly. The total dose of the external beam irradiation varied between 60 and 98 Gy for external beam radiotherapy alone and 10 Gy to 82 Gy for combined external beam radiotherapy and iodine seeds. One to 4 iodine seeds with a median activity of 21.05 MBq were permanently implanted 3 days before the start of external radiotherapy or 6 and 7 iodine seeds alone were used. The median tumor volume at the start of treatment was 0.12 cm{sup 3}. Local tumor control rates were determined and TCD{sub 37%} values were calculated applying the maximum likelihood method. Results: With increasing number of implanted iodine seeds the TCD{sub 37%} (of external beam irradiation) decreased. With external beam radiotherapy alone the TCD{sub 37%} amounted to 103.2 Gy (95% CI, 101.3 to 105.1 Gy) decreasing to (externally applied doses) 69.7 Gy (63.7 to 74.7 Gy) after 1 implanted iodine seed and further to 31.6 Gy (25.6 to 37.6 Gy) after 4 implanted iodine seeds. The effective dose (equivalent to external dose) per iodine seed decreased with increasing number of implanted iodine seeds. One iodine seed gave an effective dose of 33.5 Gy (28.5 to 39.5 Gy) decreasing to 17.9 Gy (16.4 to 19.4 Gy) after 4 iodine seeds. Conclusions: The combined treatment of tumors with implanted low-dose-rate iodine seeds and external beam irradiation can decrease the total dose of the external beam irradiation and, hence, offer the possibility of considerable dose sparing of normal tissues without compromising local tumor control rates. (orig.) [German] Hintergrund: Pruefung des Effekts der Kombination von permanent implantierten Low-Dose-Rate-Jod-125-Seeds und fraktionierter externer Bestrahlung auf die lokalen Tumorkontrollraten in einem experimentellen Tumorsystem. Material und Methoden: Die Experimente wurden am Rhabdomyosarkom R1H der Ratte durchgefuehrt, welches subkutan auf den Ruecken von WAG/Raj-Albinoratten transplantiert wurde. Die Tumoren wurden mit 200 kVp Roentgenstrahlen mit 2 Gy/Fraktion fuenfmal woechentlich bestrahlt. Die Gesamtdosen der externen Bestrahlung variierten zwischen 60 und 98 Gy fuer alleinige externe Bestrahlung und 10 und 82 Gy fuer die Kombination aus externer Bestrahlung und implantierten Jod-Seeds. Ein bis vier Jod-Seeds mit einer medianen Aktivitaet von 21,05 Mbq wurden drei Tage vor Beginn der externen Bestrahlung permanent in die Tumoren implantiert; als Kontrollen wurden Tumoren mit sechs bis sieben Jod-Seeds permanent implantiert ohne zusaetzliche externe Bestrahlung. Das mediane Tumorvolumen zu Behandlungsbeginn betrug 0,12 cm{sup 13}. Die lokalen Tumorkontrollraten wurden ermittelt, und die TCD{sub 37%}-Werte wurden nach der Maximum-Likelihood-Methode berechnet. Ergebnisse: Mit steigender Anzahl implantierter Jod-Seeds nahm die TCD{sub 37%} (der externen Bestrahlung) ab. Nach alleiniger externer Bestrahlung betrug die TCD{sub 37%} 103,2 Gy (95%-Vertrauensbereich 101,3 bis 105,1 Gy) und nahm nach Implantation eines Jod-Seeds auf 69,7 Gy (63,7 bis 74,7 Gy) ab bzw. 31,6 (25,6 bis 37,6 Gy) nach vier implantierten Jod-Seeds. Die effektive Dosis (aequivalent einer externen Dosis) pro Jod-Seed nahm mit der Anzahl implantierter Jod-Seeds ab. Nach Implantation eines Jod-Seeds betrug die effektive Dosis 33,5 Gy (95%-Vertrauensbereich 28,5 bis 39,5 Gy) und nahm nach vier Jod-Seeds auf 17,9 Gy (16,4 bis 19,4 Gy) ab. Schlussfolgerung: Die Kombination von externer Bestrahlung und Implantation von Jod-Seeds in Tumoren ermoeglicht eine erhebliche Verringerung der extern applizierten Dosis und damit auch eine Verringerung der Belastung von Normalgeweben ohne Gefahr niedriger Tumorkontrollraten. (orig.)
Defibrillation Testing and Early Neurologic Outcome
During implantable cardioverter-defibrillator (ICD) implantation, ventricular defibrillation testing (DFT) is considered a standard procedure. This procedure often requires multiple ventricular fibrillation (VF) inductions. These repeated short episodes of circulatory arrest with global cerebral ischemia may cause neurological damage. In the present study, patients undergoing initial ICD implantation and limited induction of VF for defibrillation safety margin testing were evaluated for pre- and postoperative cognitive and neurologic functions. In addition, the serum neuron specific enolase (NSE) level, which is a biochemical marker of cerebral injury, was evaluated. The study was performed on 16 patients undergoing initial elective transvenous insertion of an ICD. A neurologic examination and cognitive assessment tests were performed 24 to 48 hours before and after ICD. NSE was determined before (NSE 1) and at the end of the surgery (NSE 2), as well as 2 hours (NSE 3), 24 hours (NSE 4), and 48 hours (NSE 5) after implantation. A total of 29 internal shocks (average, 1.8 ± 0.4) with energy ranging from 14 to 41 J (mean, 20 ± 5; median, 20 J ) were delivered in the ICD group patients. In one patient, 3 external (50, 200 and 360 J) shocks were required for fast VT induced during ICD lead positioning. The mean duration of VF was 10 ± 4 seconds and the mean cumulative time in VF was 16 ± 5 seconds. The mean recovery time between VFs was 5.3 ± 0.6 minutes. NSE levels were not different from the baseline at any time point in the patients of the group that completed the 48-hour observation period (P > 0.05). The patients did not report any new neurological symptoms after ICD implantation, and repeat examination after the procedure showed no abnormal findings other than those detected in the previous one. There were no statistically significant differences between the preoperative and postoperative scores obtained in the cognitive assessment. Single or two VF inductions and the brief arrest of cerebral circulation during ICD implantation are not associated with permanent neurological injury. However, further studies are needed to confirm this finding.
Abstract in portuguese INTRODUÇÃO: A estenose aórtica é uma afecção prevalente e com altas taxas de morbidade e mortalidade, sendo a troca valvular cirúrgica a abordagem clássica. Indivíduos idosos e com outras comorbidades apresentam elevado risco operatório. O implante valvular aórtico percutâneo surge como alternativa à cirurgia padrão. O objetivo deste estudo é apresentar o seguimento de dois anos dos primeiros casos realizados no Sul do Brasil com essa abordagem inédita. M? (more) ?TODOS: Série de casos com descrição da técnica e resultados imediatos e a médio prazo do implante do dispositivo CoreValveTM (Medtronic Inc., Minneapolis, Estados Unidos), que consiste de uma bioprótese de pericárdio porcino montada em stent autoexpansível de nitinol, introduzido pela via arterial. RESULTADOS: Foram submetidos ao implante desse dispositivo quatro pacientes do sexo feminino, com idade variando entre 81 anos e 90 anos e EuroSCORE logístico de 20% a 36%. Observou-se significativa queda do gradiente ventrículo esquerdo-aorta, assim como ausência de complicações cardiovasculares maiores, embora duas pacientes tenham necessitado de implante de marca-passo definitivo por distúrbio de condução atrioventricular. No seguimento de dois anos observou-se melhora da classe funcional e manutenção dos gradientes e das áreas valvares aórticas alcançadas no final do procedimento e diminuição progressiva da massa ventricular esquerda. CONCLUSÕES: Esta experiência inicial com implante valvular aórtico percutâneo tem se mostrando segura e efetiva em análise a médio prazo. Estudos com seguimento a longo prazo são necessários para definir o exato papel e precisas indicações dessa nova e promissora técnica. Abstract in english BACKGROUND: Aortic stenosis is a prevalent disease with high morbidity and mortality, whose classical approach is surgical valve replacement. Elderly patients and those with other comorbidities present high surgical risk. Transcatheter aortic valve implantation is an effective alternative to standard surgery. The objective of this study is to report the 2-year follow-up of the first cases performed in Southern Brazil. METHODS: Series of cases describing the technique, imm (more) ediate and medium term results of the CoreValveTM (Medtronic Inc., Minneapolis, USA) device implantation, a porcine pericardial bioprosthesis mounted on a self expanding nitinol stent, delivered via transarterial access. RESULTS: Four female patients, with ages ranging from 81 to 90 years and a logistic EuroSCORE ranging from 20% to 36% were successfully submitted to the implantation of this device. A significant reduction in the left ventricle-aortic gradient, and no major cardiovascular complications were observed, although 2 patients required the implantation of a permanent pacemaker due to complete atrioventricular block. Improvement of functional class and maintenance of gradients and aortic valve areas obtained at the end of the procedure, as well as a progressive decrease of left ventricular mass were observed in the 2 year follow-up CONCLUSIONS: This early experience with the CoreValveTM transcatheter aortic valve implantation has proved to be safe and effective in the medium term outcome. Long-term follow-up studies are required to define the exact role and adequate indications for this new and promising technology.
Abstract in portuguese INTRODUÇÃO: A estenose aórtica grave é uma doença prevalente e de alta morbidade e mortalidade, sendo a troca valvar por meio de cirurgia cardíaca a abordagem clássica. Todavia, indivíduos idosos e com outras co-morbidades apresentam elevado risco operatório. O implante valvular aórtico percutâneo pela via retrógrada desponta como uma alternativa exeqüível e efetiva. São descritos os primeiros casos realizados no Sul do Brasil com essa abordagem inédita. M (more) ÉTODO: Série de três casos com descrição da técnica e resultados imediatos do implante do dispositivo CoreValve, que consiste de uma bioprótese com três folhetos de pericárdio porcino montados e suturados e um stent auto-expansível de nitinol, introduzido pela via arterial femoral ou ilíaca. RESULTADOS: Três pacientes do sexo feminino com 81, 85 e 90 anos de idade e EuroSCORE logístico variando de 20% a 36% foram submetidas ao implante desse dispositivo com sucesso. Houve significativa queda dos gradientes entre o ventrículo esquerdo e a aorta e ausência de complicações cardiovasculares maiores, embora duas pacientes tenham necessitado de implante de marca-passo definitivo por distúrbio de condução atrioventricular. Todas as pacientes receberam alta assintomáticas e seguem em avaliação clínica. CONCLUSÃO: A experiência inicial do Sul do Brasil com implante valvular aórtico percutâneo se mostrou segura e efetiva em análise a curto prazo. Estudos adicionais e seguimento mais prolongado ainda são necessários para definir o exato papel e as precisas indicações dessa nova e promissora técnica. Abstract in english BACKGROUND: Severe aortic stenosis is a prevalent disease with high rates of morbidity and mortality. The classic approach to its treatment is through heart valve replacement surgery. However, elderly patients and others with different comorbidities present high surgical risk. The percutaneous aortic valve implantation through a retrograde approach has emerged as a feasible and effective alternative treatment for this issue. We describe the first series of cases treated w (more) ith this new approach in the South of Brazil. METHODS: Series of three cases describing the procedure and immediate results of CoreValve device implantation. This device consists in a bioprosthesis with three porcine leafs mounted and sutured in a self-expandable nitinol stent introduced through the femoral or iliac artery. RESULTS: Three female patients aged 81, 85 and 90 years with a logistic EuroSCORE varying from 20% to 36% were successfully submitted to the implantation of this device. A significant reduction in all gradients between the left ventricle and the aorta was observed. There were no reports of major cardiovascular complications, although in two patients the implantation of a permanent pacemaker was needed due to an atrioventricular conduction disorder. All patients were discharged asymptomatic and were kept in a long-term clinical follow-up evaluation program. CONCLUSION: The initial short-term experience with the percutaneous retrograde aortic valve implantation in the south of Brazil was feasible and safe. Additional studies and long-term follow-up are still necessary in order to define the precise role and adequate indications for this new and very promising technique.
Effects of non-pulsatile flow on thrombogenesis
Congestive heart failure afflicts 4.5 million people in the US alone, with an average 5-year mortality of more than 50%. Among the most promising treatments for this condition are VADs (ventricular assist devices). While conventional pulsatile flow VADs are large and introduce some significant complications such as thrombosis, non-pulsatile axial flow VADs have potentially significant advantages in being smaller, with smaller thrombogenic surfaces. However, the long term effects of non-pulsatile flow on the vascular system are not well understood. We have investigated the effects of pulsatility of blood flow in the stenotic human carotid artery using unsteady, three-dimensional computational fluid dynamic simulations. We have found that permanent, low shear stagnation zones can develop distal to stenoses with non-pulsatile flow, potentially leading to thrombus formation. In contrast, systolic peak flow tends to flush out such stagnation zones. These results are consistent with observed thrombus formation in two patients who underwent implantation of a Jarvik 2000 LVAD.
Targeted magnetic delivery and tracking of cells using a magnetic resonance imaging system
The success of cell therapies depends on the ability to deliver the cells to the site of injury. Targeted magnetic cell delivery is an emergent technique for localised cell transplantation therapy. The use of permanent magnets limits such a treatment to organs close to the body surface or an implanted magnetic source. A possible alternative method for magnetic cell delivery is magnetic resonance targeting (MRT), which uses magnetic field gradients inherent to all magnetic resonance imaging system, to steer ferromagnetic particles to their target region. In this study we have assessed the feasibility of such an approach for cell targeting, using a range of flow rates and different super paramagnetic iron oxide particles in a vascular bifurcation phantom. Using MRT we have demonstrated that ...
