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1.
Polymers (Basel) ; 16(5)2024 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-38475308

RESUMEN

Recent studies have shown that astronauts experience altered immune response behavior during spaceflight, resulting in heightened susceptibility to illness. Resources and resupply shuttles will become scarcer with longer duration spaceflight, limiting access to potentially necessary medical treatment and facilities. Thus, there is a need for preventative health countermeasures that can exploit in situ resource utilization technologies during spaceflight, such as additive manufacturing (i.e., 3D printing). The purpose of the current study was to test and validate recyclable antimicrobial materials compatible with additive manufacturing. Antimicrobial poly(lactic acid)- and polyurethane-based materials compatible with 3D printing were assessed for antimicrobial, mechanical, and chemical characteristics before and after one closed-loop recycling cycle. Our results show high biocidal efficacy (>90%) of both poly(lactic acid) and polyurethane materials while retaining efficacy post recycling, except for recycled-state polyurethane which dropped from 98.91% to 0% efficacy post 1-year accelerated aging. Significant differences in tensile and compression characteristics were observed post recycling, although no significant changes to functional chemical groups were found. Proof-of-concept medical devices developed show the potential for the on-demand manufacturing and recyclability of typically single-use medical devices using antimicrobial materials that could serve as preventative health countermeasures for immunocompromised populations, such as astronauts during spaceflight.

2.
Clin Exp Dent Res ; 10(1): e827, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38345490

RESUMEN

BACKGROUND: Fabricating clear aligners by thermoforming three-dimensional printed dental models requires a high degree of accuracy. It is unknown whether model thickness affects the accuracy when used to thermoform aligners. PURPOSE: This research utilizes three-dimensional printed models made with differing wall thicknesses to determine its effect on their ability to withstand deformation during aligner fabrication. METHODS: A total of 50 models of different wall thickness (10 each of 0.5, 1.0, 1.5, 2.0 mm, and solid) were printed using model resin (Model V2, Formlabs) on a low-force stereolithography printer (Form 3B, Formlabs). Aligners were then fabricated using a thermal pressure forming machine (Biostar V, Great Lakes Dental Technologies) utilizing 25 s cycles to adapt 0.030″ acrylic sheets (Invisacryl, Great Lakes Dental Technologies), then removed from the models and sprayed with a contrast powder (Optispray, Dentsply Sirona) to aid in scanning with an intraoral scanner (CEREC Primescan, Dentsply Sirona). Each aligner's data was then compared to the original file used for printing with 3D comparison software (Geomagic Control X, 3D Systems). RESULTS: The results show model thickness greater than or equal to 2.0 mm produced clinically acceptable results within the margin of error (0.3 mm). A total of 0.5 mm thickness failed to withstand thermal forming in 4 of the 10 trials. A total of 0.5 mm produced 27.56% of results in tolerance, 1.0 mm produced 75.66% of results in tolerance, 1.5 mm had 80.38% of results in tolerance, 86.82% of 2 mm models were in tolerance, and solid had 96.45% of results in tolerance. CONCLUSION: Hollow models of thicknesses 2.0 mm and solid models produced clinically acceptable aligners while utilizing less resin per unit compared to solid models, thus being more cost effective, time efficient and eco-friendly. Therefore, a recommendation can be made to print hollow models with a shell thickness of greater than 2.0 mm for aligner fabrication.


Asunto(s)
Polimetil Metacrilato , Impresión Tridimensional , Programas Informáticos
3.
J Dent Educ ; 87 Suppl 3: 1852-1853, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37042159
4.
J Prosthet Dent ; 2022 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-36207166

RESUMEN

A patient presented with a treatment plan for the replacement of his maxillary complete removable denture and mandibular implant-retained complete overdenture because of excessive wear and fracture of his existing prostheses. A digital workflow was used, and his dentures were milled from a monolithic acrylic resin disk. Upon delivery of the dentures, the patient reported that he was unable to sleep without his dentures in place although he denied a diagnosis of obstructive sleep apnea. After emphasizing the recommendation to remove his dentures while sleeping, it was decided to use additive manufacturing technology because of its low cost and ability to faithfully reproduce a 3-dimensional file in various biocompatible materials. The second set of sleeping dentures were 3-dimensionally printed and delivered with minimal adjustment and at a low cost.

5.
Gen Dent ; 70(1): 18-21, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34978984

RESUMEN

In-office printing of surgical guides is becoming increasingly common in the modern dental practice. This in vitro study sought to evaluate the accuracy of fit of surgical guides printed with 4 low-cost desktop 3-dimensional (3D) printers: SparkMaker Original, Photon, MP Mini SLA, and Epax X1. All of the printers in this study were released after 2017 and purchased for less than $500. All of the 3D printers were capable of printing biocompatible surgical guide resin. To evaluate the accuracy of the printers, a total of 20 surgical guides were produced with the 4 printers (n = 5) from the same stereolithography (STL) file using the same resin. The guides were then scanned with a laboratory scanner, and the intaglio surface was compared to the master STL file using metrology software. The null hypothesis was that, across printers, the intaglio surfaces of the printed surgical guides would achieve the standard of at least 80% of the surface fitting within a 100- µm tolerance level. Data were analyzed with the Tukey-Kramer test (P < 0.05). Three of the 4 printers (SparkMaker Original, Photon, and Epax X1) were able to consistently produce surgical guides within the accepted tolerance values. The Epax X1 surgical guide group had a significantly higher mean percentage of fit within the tolerance level (P < 0.05), indicating that this printer produced the greatest accuracy relative to the original STL file.


Asunto(s)
Diseño Asistido por Computadora , Implantes Dentales , Humanos , Impresión Tridimensional , Programas Informáticos , Estereolitografía
6.
J Prosthet Dent ; 127(5): 695-697, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-33454118

RESUMEN

A combined conventional and digital workflow is described to print a 3-dimensional complete-arch reduction guide. This was used to prepare guide planes with cross-arch parallelism in the distal of both maxillary first molars, the mesial of both maxillary first premolars, and the distolingual of both maxillary central incisors for a patient requiring a removable partial denture to replace missing bilateral maxillary lateral incisors and canines. The 3-dimensionally printed guide was placed on the remaining teeth in the arch and used as both a visual guide and a guide for tooth preparation.


Asunto(s)
Incisivo , Corona del Diente , Diente Premolar , Humanos , Maxilar , Diente Molar , Flujo de Trabajo
9.
Lasers Med Sci ; 36(2): 249-258, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32770424

RESUMEN

This narrative review analyses the Australian Guideline (2018) for the treatment of knee osteoarthritis (KOA) developed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The Guideline recommended against the use low-level laser therapy (LLLT). Why this conclusion was reached is discussed in this review in the context of evidence provided in other systematic reviews, the latest of which was published in 2019 and which provided strong support for LLLT for knee OA. We evaluated the reference list cited for the recommendation "against" LLLT and compared this with reference lists of systematic reviews and studies published before and after the publication date of the Guideline. Eight randomised controlled trials (RCTs) of LLLT were cited in the Guideline the latest of which was published in 2012. There were seventeen additional RCTs, five of which together with one systematic review were located in the year of publication, 2018. The most recent systematic review in 2019 included 22 RCTs in its analysis. Discordance with the levels of evidence and recommendations was identified. Although GRADE methodology is said to be robust for systematically evaluating evidence and developing recommendations, many studies were not identified in the Guideline. In contrast, the latest systematic review and meta-analysis provides robust evidence for supporting the use of LLLT in knee OA. The conflict between guidelines based on opinion and evidence based on meta-analysis is highlighted. Given the totality of the evidence, we recommend that the Australian Guideline should be updated immediately to reflect a "for" recommendation.


Asunto(s)
Terapia por Luz de Baja Intensidad , Osteoartritis de la Rodilla/radioterapia , Guías de Práctica Clínica como Asunto , Australia , Humanos , Metaanálisis como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Revisiones Sistemáticas como Asunto
10.
Photobiomodul Photomed Laser Surg ; 38(4): 206-214, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32186975

RESUMEN

Objective: To determine the potential efficacy and feasibility of photobiomodulation therapy (PBMT) before and after knee arthroplasty (KA) surgery. Background: Total knee replacements (total knee arthroplasty, TKA) are one of the most common and successful surgical interventions for osteoarthritis. Up to 20,000 knee replacement arthroplasties are performed in Australia annually. Although TKA aims to restore knee alignment and relieve pain in the long term, the initial post-operative period is difficult and rehabilitation is often hindered by persistent pain and swelling. A promising therapeutic approach, PBMT using a novel self-adhesive light patch system, may be feasible for reducing post-operative pain and swelling and aiding recovery. Materials and methods: This is an interventional clinical feasibility study protocol. Patients from a surgical waitlist will be invited to take part. PBMT will be applied for 30 min daily for 7 days pre-operatively using a novel light patch system (CareWear®) with both 450 nm (6.75 mW/cm2) and 640 nm (2.25 mW/cm2) microdiodes. Post-operative treatment will utilize the same device second daily for 1 week after removal of compression bandages. Results: Outcomes will be evaluated at seven time points: baseline at week 1 pre-operatively, 1 day before surgery, day 4 after surgery, weekly for a further 2 weeks, and fortnightly until 6 weeks post-hospital discharge. Outcome measures include the following: Numeric Pain Rating Scale, stair climb test, 30-sec chair stand test, timed up and go test, 40-m fast-paced walk test, modified Iowa Level of Assistance Scale, muscle strength, knee range of motion, Knee Injury and Osteoarthritis Outcome Score, and Lower Limb Functional Index. Conclusions: This study will provide an assessment of feasibility of using PBMT applied using a novel light patch system for management of pain symptoms and swelling, and aiding recovery of patients undergoing TKA. The results of this feasibility study will contribute to planning of the design and methods of a large clinical trial.


Asunto(s)
Artroplastia de Reemplazo de Rodilla/métodos , Terapia por Luz de Baja Intensidad/instrumentación , Osteoartritis de la Rodilla/terapia , Complicaciones Posoperatorias/prevención & control , Artroplastia de Reemplazo de Rodilla/efectos adversos , Estudios de Factibilidad , Humanos , Terapia por Luz de Baja Intensidad/métodos , Cuidados Posoperatorios , Complicaciones Posoperatorias/etiología , Cuidados Preoperatorios
11.
Ann Allergy Asthma Immunol ; 120(2): 164-168.e1, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29290515

RESUMEN

BACKGROUND: Asthma in older adults is associated with increased morbidity and mortality compared with asthma in younger patients. Fixed airflow obstruction (FAO) is associated with decreased survival in younger patients, but its significance remains unclear in older adults with asthma. OBJECTIVE: To identify risk factors and outcomes related to FAO in older adults with asthma. METHODS: Subjects older than 55 years with a physician diagnosis of persistent asthma were evaluated. Collected data included participant demographic information, medications, asthma exacerbations, Asthma Control Test (ACT) score, Asthma Quality of Life (AQLQ) score, comorbidities, spirometry, atopic status, and fractional exhaled nitric oxide. Clinical characteristics and outcomes associated with FAO (defined as post-bronchodilator ratio of forced expiratory volume in 1 second to forced vital capacity ≤70%) were assessed. RESULTS: A total of 186 participants were analyzed (48 men and 138 women, mean age 66 years). FAO was demonstrated in 30% of participants. Using regression analysis, predictors of FAO included advanced age, African American race, male sex, and longer duration of asthma. In outcomes analysis, FAO was associated with worsened ACT and AQLQ scores; however, after controlling for confounding factors, logistic regression showed no association. No significant association was found between FAO and exacerbations, fractional exhaled nitric oxide, atopy, rhinitis, education level, depression, smoking, or body mass index. CONCLUSION: Risk factors associated with FAO in older adults with asthma include advanced age, African American race, increased asthma duration, and male sex. Unlike younger patients, FAO is not independently associated with worsened asthma control, quality of life, or exacerbations in older patients with asthma. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01979055.


Asunto(s)
Factores de Edad , Obstrucción de las Vías Aéreas/epidemiología , Asma/epidemiología , Negro o Afroamericano , Factores Sexuales , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Factores de Riesgo , Espirometría , Estados Unidos/epidemiología
12.
J Crit Care ; 43: 75-80, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28850931

RESUMEN

OBJECTIVES: Currently no national standard exists on optimal timing to initiate VTE chemoprophylaxis after traumatic brain injury (TBI). We designed this survey to assess current practice regarding the timing of VTE chemoprophylaxis after TBI. METHODS: All the EAST members were surveyed online. Participants reported demographics, and responses to questions regarding VTE chemoprophylaxis in TBI and timing of chemoprophylaxis in 2 hypothetical clinical scenarios of TBI. RESULTS: Three hundred and ninety-one full responses were collected (response rate 30.9%). Most respondents (75%) reported the decision to initiate VTE chemoprophylaxis with a consensus between the neurosurgery and trauma/critical care services. While 76% of respondents reported experience of seeing pulmonary embolism without chemoprophylaxis, 44% witnessed progression of TBI after VTE chemoprophylaxis. Approximately 50% considered their practice of VTE chemoprophylaxis in TBI patients to be conservative. Almost 50% reported no standardized protocol in their institutions. While 1/3 of the members believed guidelines exist, another 1/3 believed no guidelines available. Responses to two clinical scenarios showed various approaches regarding the timing of VTE chemoprophylaxis. CONCLUSIONS: Currently there is a wide variability in the practice patterns regarding the timing of VTE chemoprophylaxis in TBI patients. This survey reinforces the need for further investigation to guide clinical practice.


Asunto(s)
Anticoagulantes/uso terapéutico , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Tromboembolia Venosa/prevención & control , Adulto , Quimioprevención/métodos , Consenso , Cuidados Críticos/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pautas de la Práctica en Medicina/estadística & datos numéricos , Embolia Pulmonar/tratamiento farmacológico , Encuestas y Cuestionarios , Factores de Tiempo , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/terapia
13.
Am J Med Genet A ; 170(11): 2960-2964, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27481052

RESUMEN

Chronic histiocytic intervillositis (CHI) is characterized by the presence of histiocytes within the intervillous space of the placenta. The pathogenesis is unclear but available evidence supports an alloimmune mechanism on the basis of the presence in maternal blood of HLA antibodies directed against paternal HLA antigens. CHI has a high risk of recurrence and of abnormal perinatal outcomes. Little is known about the effects of CHI on the developing fetus, in particular on the growth and development of the skeleton. We have studied a woman whose third pregnancy was terminated after ultrasonography showed severe intrauterine growth restriction, raising the possibility of a lethal skeletal dysplasia. Postmortem radiographs showed multiple fractures and other signs of osteogenesis imperfecta (OI). However, bone histology was not typical of OI and no abnormalities were identified by sequencing OI genes. The subsequent pregnancy was also severely growth restricted and was terminated. The placenta showed chronic histiocytic intervillositis, which, on retrospective review, had also been present in her second and third pregnancies. Her fifth pregnancy was again associated with intrauterine growth restriction and CHI but resulted in a premature birth. CHI can be associated with radiographic features that mimic OI and should be considered when fetal fractures occur in the context of recurrent miscarriage, fetal death in utero, and intrauterine growth restriction. The correct diagnosis can be made by histopathology of the placenta, supported by bone histology and normal results of molecular studies for OI. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Enfermedades Óseas Metabólicas/diagnóstico , Retardo del Crecimiento Fetal/diagnóstico , Fracturas Óseas/diagnóstico , Histiocitos/patología , Placenta/patología , Adulto , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Biomarcadores , Huesos/diagnóstico por imagen , Huesos/patología , Enfermedad Crónica , Femenino , Histiocitos/metabolismo , Humanos , Inmunohistoquímica , Embarazo , Radiografía , Recurrencia
15.
Case Rep Pediatr ; 2015: 796151, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25861505

RESUMEN

Neurologic outcomes following pediatric cardiac arrest are consistently poor. Early initiation of cardiopulmonary resuscitation has been shown to have positive effects on both survival to hospital discharge, and improved neurological outcomes after cardiac arrest. Additionally, the use of therapeutic hypothermia may improve survival in pediatric cardiac arrest patients admitted to the intensive care unit. We report a child with congenital hypertrophic obstructive cardiomyopathy and an out-of-hospital cardiac arrest, in whom the early initiation of effective prolonged cardiopulmonary resuscitation and subsequent administration of therapeutic hypothermia contributed to a positive outcome with no gross neurologic sequelae. Continuing efforts should be made to promote and employ high-quality cardiopulmonary resuscitation, which likely contributed to the positive outcome of this case. Further research will be necessary to develop and solidify national guidelines for the implementation of therapeutic hypothermia in selected subpopulations of children with OHCA.

16.
Allergy Asthma Proc ; 36(1): 70-3, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25562559

RESUMEN

Hereditary angioedema (HAE) is a rare disease that causes recurrent mucosal and cutaneous swelling. Skin swelling, abdominal pain, and airway swelling cause significant morbidity and potential mortality. Symptoms often appear early in life and accelerate around puberty. Despite this, there is a paucity of both data and treatment options for HAE in children in the United States. Our objective was to summarize the published data and perform a retrospective chart review on children with HAE to improve care of the child with the disease. A retrospective chart review study was performed after Institutional Review Board approval. A search of electronic medical records from 2001 to 2011 was performed for children aged 1 to 18 years with a confirmed diagnosis of HAE. Demographic patient information was obtained and analyzed. Twenty-five pediatric patients were identified with the diagnosis of HAE: 13 female and 12 male. The median age at diagnosis was seven years. The most common initial presenting symptom was swelling of the upper extremity, followed by abdominal pain, swelling of the face and/or lower extremity, and scrotal swelling. Three patients reported no previous symptoms and were diagnosed due to family history of HAE and positive laboratory testing. The majority of patients (84%) reported a family history of HAE. Accurate and timely diagnosis of HAE is imperative for children to prevent further morbidity and mortality associated with the disease.


Asunto(s)
Angioedemas Hereditarios/epidemiología , Adolescente , Angioedemas Hereditarios/diagnóstico , Angioedemas Hereditarios/tratamiento farmacológico , Niño , Preescolar , Comorbilidad , Proteínas Inactivadoras del Complemento 1/uso terapéutico , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos
17.
J Am Osteopath Assoc ; 114(3 Suppl 1): S6-12, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24636971

RESUMEN

Vaccination is a safe and effective tool in the prevention of serious and deadly infectious diseases. The vaccinations delivered at routine adolescent visits are an integral part of preventing infection, as well as reducing school absenteeism as a result of illness. Current recommendations by the Advisory Committee on Immunization Practices include vaccinating during a single visit at age 11 or 12 years against pathogens including Neisseria meningitidis, which has been shown to cause invasive meningococcal infections; Bordetella pertussis, which has been shown to cause pertussis (whooping cough); and human papillomavirus, which has been shown to cause cervical cancer and genital warts. Additionally, annual influenza vaccination is recommended for adolescents without contraindications to the vaccine. In the present article, the authors summarize current recommendations for adolescent vaccines and their formulations, the infections that they prevent, contraindications to administration, vaccination rates, and the most commonly reported adverse events.


Asunto(s)
Programas de Inmunización/normas , Vacunación/normas , Vacunas/farmacología , Adolescente , Humanos , Esquemas de Inmunización
18.
J Toxicol Environ Health A ; 76(17): 1015-22, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24168037

RESUMEN

Nitrate and atrazine (ATR) occur in combination in some drinking-water supplies and might react to form N-nitrosoatrazine (NNAT), which is reportedly more toxic than nitrate, nitrite, or ATR. Current evidence from population-based studies indicates that exposure to nitrate, nitrite, and nitrosatable compounds increases the risk of congenital defects and/or rate of embryo lethality. To test the hypothesis that NNAT induces malformations during embryogenesis, chicken embryos were examined for lethality and developmental abnormalities after treating fertilized eggs with 0.06-3.63 µg NNAT. After 5 d of incubation (Hamburger and Hamilton stage 27), 90% of embryos in NNAT-treated eggs were alive, of which 23% were malformed. Malformations included heart and neural-tube defects, caudal regression, gastroschisis, microphthalmia, anophthalmia, and craniofacial hypoplasia. The findings from this investigation suggest further studies are needed to determine the mechanisms underlying NNAT-induced embryotoxicity.


Asunto(s)
Anomalías Inducidas por Medicamentos/etiología , Atrazina/análogos & derivados , Nitrosaminas/toxicidad , Animales , Atrazina/toxicidad , Embrión de Pollo/efectos de los fármacos , Embrión de Pollo/crecimiento & desarrollo , Anomalías Craneofaciales/inducido químicamente , Microftalmía/inducido químicamente , Defectos del Tubo Neural/inducido químicamente
19.
Pediatrics ; 127(6): e1386-91, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21555492

RESUMEN

OBJECTIVE: The goal of this study was to define self-embedding behavior (SEB), develop a clinical profile of adolescents who engage in SEB, and emphasize the importance of rapid, targeted, and effective identification and intervention. METHODS: As part of a retrospective study with a database evaluating 600 patients percutaneously treated for soft-tissue foreign body removal, adolescents were identified with self-embedded soft-tissue foreign bodies. We describe patients' gender, age, and psychiatric diagnoses; SEB age of onset, frequency, and self-reported reasons; and the number, type, location of, and removal technique for objects. RESULTS: Eleven patients (9 females) who engaged in SEB were identified. Ten of the 11 patients were members of a group home or psychiatric facility at the time they engaged in SEB. All patients had previous and multiple psychiatric diagnoses. SEB mean age-of-onset was 16 years, and mean number of SEB episodes per patient was 1.9. The most common self-reported purpose for SEB was suicidal ideation (6 of 8 [75%]) versus nonsuicidal ideation (2 of 8 [25%]), with 3 cases lacking this documentation. The mean number of objects embedded in a single episode was 2.4, usually composed of metal and embedded in the arm. Seventy-six foreign bodies were percutaneously removed (using ultrasound or fluoroscopic guidance), including metal, glass, wood, plastic, graphite, and crayon. CONCLUSIONS: SEB is an extreme form of self-injury requiring aggressive and timely interdisciplinary assessment and treatment. An understanding of SEB allows medical professionals to pursue rapid, targeted, and effective intervention to interrupt the cycle of self-harm and institute appropriate long-term therapy.


Asunto(s)
Cuerpos Extraños/prevención & control , Atención Primaria de Salud/métodos , Conducta Autodestructiva/prevención & control , Ideación Suicida , Adolescente , Femenino , Estudios de Seguimiento , Cuerpos Extraños/psicología , Humanos , Masculino , Estudios Retrospectivos , Conducta Autodestructiva/psicología
20.
Drug Metab Dispos ; 38(12): 2309-19, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20823292

RESUMEN

3A5 is a novel antibody that binds repeated epitopes within CA125, an ovarian tumor antigen that is shed into the circulation. Binding to shed antigen may limit the effectiveness of therapeutic antibodies because of unproductive immune complex (IC) formation and/or altered antibody distribution. To evaluate this possibility, we characterized the impact of shed CA125 on the in vivo distribution of 3A5. In vitro, 3A5 and CA125 were found to form ICs in a concentration-dependent manner. This phenomenon was then evaluated in vivo using quantitative whole-body autoradiography to assess the tissue distribution of (125)I-3A5 in an orthotopic OVCAR-3 tumor mouse model at different stages of tumor burden. Low doses of 3A5 (75 µg/kg) and pathophysiological levels of shed CA125 led to the formation of ICs in vivo that were rapidly distributed to the liver. Under these conditions, increased clearance of 3A5 from normal tissues was observed in mice bearing CA125-expressing tumors. Of importance, despite IC formation, 3A5 uptake by tumors was sustained over time. At a therapeutically relevant dose of 3A5 (3.5 mg/kg), IC formation was undetectable and distribution to normal tissues followed that of blood. In contrast, increased levels of radioactivity were observed in the tumors. These data demonstrate that CA125 and 3A5 do form ICs in vivo and that the liver is involved in their uptake. However, at therapeutic doses of 3A5 and clinically relevant CA125 levels, IC formation consumes only a minor fraction of 3A5, and tumor targeting seems to be unaffected.


Asunto(s)
Anticuerpos/metabolismo , Complejo Antígeno-Anticuerpo/metabolismo , Antígeno Ca-125/inmunología , Neoplasias Ováricas/inmunología , Animales , Línea Celular Tumoral , Femenino , Humanos , Ratones , Distribución Tisular
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