Endoscopic analysis of alterations in sinus floor elevation approaching the summers technique and immediate implant: a clinical trial with 10 years follow-up / Análise endoscópica das alterações na elevação do assoalho do seio maxilar com abordagem da técnica de Summer e implante imediato: um ensaio clínico com 10 anos de acompanhamento

The goal of this study was to evaluate by endoscopy, possible intercurrences during the sinus floor lifting employing the Summers technique, besides verify the implants' survival rate after 10 years. Six patients (12 sinus) were included in this study. The same surgeon performed the procedures, under local anesthesia and venous sedation in the hospital. All participants underwent sinus lift and implant placement in only one procedure, as previously planned, using endoscopic analysis (Stortz®). All cases received bovine bone graft (Bio-Oss®) before the implant placement. After 10 years, the patients were recalled for follow-up. Two intercurrences (16.66%) were detected using the endoscope, one simple rupture, and another perforation with the leaking of the graft within the sinus. Both were reverted and corrected immediately. There was one implant loss (8.33%), therefore this patient did not undergo any intercurrence in transoperative, and the membrane was elevated lesser than 5 mm. The survival rate reached was 91.66%. The osteotome technique constitutes a reliable method with a long-term of 10 years presenting a high implant survival rate, suggesting an elevation up to 5.5 mm in healthy patients. The occurrences in transoperative were only detected by the endoscopic analysis which must be stimulated to guarantee more secure visibility. Otherwise, the association the atraumatic technique and endoscope was tough, increased the costs, limiting the use routinely.

O objetivo deste estudo foi avaliar através de endoscopia as possíveis intercorrências durante levantamento de seio maxilar fechado, além de verificar a taxa de sobrevivência dos implantes após 10 anos. Seis pacientes (12 seios maxilares) foram incluídos neste estudo com idades entre 26 e 74 anos. O mesmo cirurgião realizou os procedimentos, sob anestesia local e sedação venosa em ambiente hospitalar. Todos os participantes foram submetidos à elevação do seio nasal e colocação do implante em apenas um procedimento, conforme planejado anteriormente, por acompanhamento transcirúrgico da endoscopia (Stortz®). Todos os casos receberam enxerto ósseo bovino (Bio-Oss®) antes da colocação do implante. Após 10 anos, os pacientes foram chamados para acompanhamento. Foram detectadas duas intercorrências (16,66%) com o endoscópio, uma ruptura simples e outra perfuração com extravasamento do enxerto para dentro do seio. Ambos foram revertidos e corrigidos imediatamente. Houve perda de um implante (8,33%), portanto esse paciente não apresentou intercorrência no transoperatório e a membrana estava elevada menos de 5 mm. A taxa de sobrevivência alcançada foi de 91,66%. A técnica do osteótomo constitui um método confiável em longo prazo (10 anos) apresentando uma alta taxa de sobrevivência do implante, sugerindo que uma elevação de até 5,5 mm em pacientes saudáveis é possível. Assim, verificou-se que as ocorrências no transoperatório foram detectadas apenas pela análise endoscópica que deve ser estimulada para garantir uma visibilidade mais segura. Por outro lado, a associação da técnica fechada com o endoscópio foi difícil, aumentou os custos, limitando seu uso como rotina

Laboratory Guidelines for Animal Care.

Animal research is a controversial subject because of the ethical and moral implications of using unwilling research subjects in potentially painful or distressful procedures usually ending in euthanasia. As such, it must be conducted in a compassionate and responsible manner geared toward maximizing the animals' quality of life prior to and during experimentation. Because of its contentious nature, the conduct of animal research is highly regulated at the federal, state, city, and institutional levels. It is essential that researchers acquire a thorough knowledge of the procedures to be conducted as well as a working knowledge of the regulations. This will maximize humane care of research animals and prevent potentially negative or detrimental interactions with groups opposed to using animals in biomedical research. Perhaps the best way to attain these goals is to avoid inadvertent instances of noncompliance with their research protocol or applicable regulations. Regulatory noncompliance can also have serious negative consequences on investigators' research careers ranging from temporary suspension of their protocols to loss of funding and revocation of principal investigator status and associated privileges. To minimize such adverse outcomes, it is advised that researchers build positive and collaborative relationships with key institutional players such as the veterinary staff, the Institutional Animal Care and Use Committee (IACUC), and top administrators. Guidance is provided regarding the appropriate handling of regulatory noncompliance.

Aplicação do mapeamento genético molecular para o diagnóstico de Síndrome de Apert ­ uma abordagem multidisciplinar / Application of molecular genetic mapping for the diagnosis of Apert's Syndrome ­ a multidisciplinary approach

A Síndrome de Apert é uma doença congênita rara caracterizada por fusão prematura da sutura coronal e estenose (disfunção) craniofacial grave, mas também exibe muitos outros defeitos cardíacos e pulmonares, bem como malformações neurais que podem levar a problemas cognitivos, na maior parte dos casos a anomalia é resultante de uma mutação paternal, afetando 1 a cada 160.000 nascidos vivos, com elevada incidência em asiáticos. A literatura escreve que essa síndrome é consequência de mutações do gene do fator de crescimento receptor 2 (FGFR2), abrangendo dois aminoácidos adjacentes, que ocorrem durante o processo de formação. Concluiu-se que o paciente com esse tipo de comprometimento requer acompanhamento multidisciplinar de longo prazo pela maioria dos danos não serem aparentes nas fases iniciais de vida, pelas patologias dentoesqueléticas, necessitando de tratamento odontológico periodicamente (AU).

Apert Syndrome is a rare congenital disease characterized by premature fusion of the coronal suture and severe craniofacial stenosis (dysfunction), but also exhibits many other cardiac and pulmonary defects as well as neural malformations that can lead to cognitive problems, in most cases anomaly is the result of a paternal mutation, affecting 1 in 160,000 live births, with high incidence in Asian people. Literature writes that this syndrome is a consequence of mutations of the growth factor receptor 2 (FGFR2) gene encompassing two adjacent amino acids that occur during the formation process. It is concluded that the patient with this type of impairment requires long-term multidisciplinary follow-up because most of the damages are not apparent in the early stages of life due to dentoskeletal pathologies requiring dental treatment periodically (AU).

Distribution of phenolic compounds and antioxidant capacity in apples tissues during ripening.

The effect of variety and ripening stage on the distribution of phenolic compounds and in vitro antioxidant capacity of Gala, Fuji Suprema and Eva apples were evaluated. Hydroxycinnamic acids, flavonoids, flavanols, flavonols, dihydrochalcones and antioxidant activity (FRAP and DPPH) were assessed in the epicarp, mesocarp and endocarp of three varieties at three ripening stages (unripe, ripe and senescent). The Fuji Suprema variety distinguished by its content of flavonols at senescent stage, while Eva variety distinguished by its content of dihydrochalcones (unripe stage) and anthocyanins (ripe stage). In general, phenolic acids and flavonoids decreased with ripening in the epicarp and endocarp. However, in the mesocarp, the effect of ripening was related with the apple variety. Hierarchical cluster analysis confirmed the influence of ripening in the apple tissue. The evolution of these compounds during ripening occurred irregularly and it was influenced by the variety.

Comparison of the protective effect of a commercially available western diamondback rattlesnake toxoid vaccine for dogs against envenomation of mice with western diamondback rattlesnake (Crotalus atrox), northern Pacific rattlesnake (Crotalus oreganus oreganus), and southern Pacific rattlesnake (Crotalus oreganus helleri) venom.

OBJECTIVE: To evaluate effectiveness of a commercially available toxoid manufactured from western diamondback (WD) rattlesnake (Crotalus atrox) venom against envenomation of mice with WD, northern Pacific (NP) rattlesnake (Crotalus oreganus oreganus), and southern Pacific (SP) rattlesnake (Crotalus oreganus helleri) venom. ANIMALS: 90 specific pathogen-free female mice. PROCEDURES: Mice were allocated into 3 cohorts (30 mice/cohort). Mice received SC injections of C atrox toxoid (CAT) vaccine (n = 15/group) or adjuvant (15/group) at day 0 and again at 4 weeks. At 8 weeks, mice were challenge-exposed with 1 of 3 venoms. Survival until 48 hours was evaluated by use of log-rank analysis of survival curves and the z test for proportions. RESULTS: 6 of 15 WD-challenged CAT-vaccinated mice, 3 of 15 NP-challenged CAT-vaccinated mice, and 0 of 15 SP-challenged CAT-vaccinated mice survived until 48 hours. All adjuvant-only vaccinates survived ≤ 21 hours. Mean survival time of CAT vaccinates was longer than that of adjuvant-only vaccinates for all venoms (1,311 vs 368 minutes for WD, 842 vs 284 minutes for NP, and 697 vs 585 minutes for SP). Results of the z test indicated a significantly increased survival rate for vaccinates exposed to WD rattlesnake venom but not for vaccinates exposed to NP or SP rattlesnake venom. Log-rank analysis revealed a significant difference between survival curves of vaccinated versus unvaccinated mice exposed to NP but not WD or SP venom. CONCLUSIONS AND CLINICAL RELEVANCE: CAT vaccination improved survival rate and survival time after challenge exposure with WD rattlesnake venom and may offer limited protection against NP rattlesnake venom but did not provide significant cross-protection against SP rattlesnake venom.

Core body temperature as adjunct to endpoint determination in murine median lethal dose testing of rattlesnake venom.

Median lethal dose (LD50) testing in mice is the 'gold standard' for evaluating the lethality of snake venoms and the effectiveness of interventions. As part of a study to determine the murine LD50 of the venom of 3 species of rattlesnake, temperature data were collected in an attempt to more precisely define humane endpoints. We used an 'up-and-down' methodology of estimating the LD50 that involved serial intraperitoneal injection of predetermined concentrations of venom. By using a rectal thermistor probe, body temperature was taken once before administration and at various times after venom exposure. All but one mouse showed a marked, immediate, dose-dependent drop in temperature of approximately 2 to 6°C at 15 to 45 min after administration. The lowest temperature sustained by any surviving mouse was 33.2°C. Surviving mice generally returned to near-baseline temperatures within 2 h after venom administration, whereas mice that did not survive continued to show a gradual decline in temperature until death or euthanasia. Logistic regression modeling controlling for the effects of baseline core body temperature and venom type showed that core body temperature was a significant predictor of survival. Linear regression of the interaction of time and survival was used to estimate temperatures predictive of death at the earliest time point and demonstrated that venom type had a significant influence on temperature values. Overall, our data suggest that core body temperature is a useful adjunct to monitoring for endpoints in LD50 studies and may be a valuable predictor of survival in venom studies.

Sistemas adesivos - classificação / Adhesives systems - classification

Os adesivos dentários são combinações de monômeros resinosos hidrofílicos e hidrofó- bicos, de diferentes pesos moleculares e solventes, que estabelecem ligação entre o material restaurador e a estrutura dentária após polimerização. Sistemas adesivos atuais são indicados para diversas aplicações odontológicas e classificados como condicionamento total (etch-and- -rinse) ou autocondicionamento (self-etching) e sua intenção de uso difere no número de etapas de aplicação e como eles interagem com as estruturas dentais naturais.

Dentin adhesives are combinations of hydrophilic and hydrophobic monomers, with different molecular weights and solvents that connect the restorative material to the tooth structure after polymerization. Current adhesive systems are suitable for various dental applications and classified as etch-and-rinse or self-etching. The purpose of their use differs according to the number of application steps and how they interact with the natural dental structures.

INDs for PET molecular imaging probes-approach by an academic institution.

We have developed an efficient, streamlined, cost-effective approach to obtain Investigational New Drug (IND) approvals from the Food and Drug Administration (FDA) for positron emission tomography (PET) imaging probes (while the FDA uses the terminology PET drugs, we are using "PET imaging probes," "PET probes," or "probes" as the descriptive terms). The required application and supporting data for the INDs were collected in a collaborative effort involving appropriate scientific disciplines. This path to INDs was successfully used to translate three [(18) F]fluoro-arabinofuranosylcytosine (FAC) analog PET probes to phase 1 clinical trials. In doing this, a mechanism has been established to fulfill the FDA regulatory requirements for translating promising PET imaging probes from preclinical research into human clinical trials in an efficient and cost-effective manner.

Repressive effect of primary virus replication on superinfection correlated with gut-derived central memory CD4(+) T cells in SHIV-infected Chinese rhesus macaques.

A possible mechanism of susceptibility to superinfection with simian-human immunodeficiency virus (SHIV)-1157ipd3N4 was explored in twelve SHIVSF162P3-infected Chinese rhesus macaques. Based on the kinetics of viral replication for the second infecting virus following SHIV-1157ipd3N4 inoculation, the monkeys were divided into two groups: those relatively resistant to superinfection (SIR) and those relatively sensitive to superinfection (SIS). We found that superinfection-resistant macaques had high primary viremia, whereas superinfection-sensitive macaques had low primary viremia, suggesting that primary SHIVSF162P3 infection with a high viral-replication level would repress superinfection with a heterologous SHIV-1157ipd3N4. Although no correlation of protection against superinfection with virus-specific CD4(+) T cell or CD8(+) T cell immune responses from gut was observed prior to superinfection, superinfection susceptibility was strongly correlated with CD4(+) Tcm cells from gut both prior to the second infecting virus inoculation and on day 7 after superinfection, but not with CD4(+) Tem cells from gut or with CD4(+) Tcm cells from peripheral blood and lymph node. These results point to the important roles of gut-derived CD4(+) Tcm cells for the study of the mechanisms of protection against superinfection and the evaluation of the safety and efficacy of vaccines and therapies against acquired immune deficiency syndrome (AIDS).

Classification of juices and fermented beverages made from unripe, ripe and senescent apples based on the aromatic profile using chemometrics.

The aim of this study was to assess differences between apple juices and fermented apple beverages elaborated with fruits from different varieties and at different ripening stages in the aroma profile by using chemometrics. Ripening influenced the aroma composition of the apple juice and fermented apple. For all varieties, senescent fruits provided more aromatic fermented apple beverages. However, no significant difference was noticed in samples made of senescent or ripe fruits of the Lisgala variety. Regarding the juices, ripe Gala apple had the highest total aroma concentration. Ethanal was the major compound identified in all the samples, with values between 11.83mg/L (unripe Lisgala juice) and 81.05mg/L (ripe Gala juice). 3-Methyl-1-butanol was the major compound identified in the fermented juices. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were applied and classified the juices and fermented juices based on physicochemical and aroma profile, demonstrating their applicability as tools to monitor the quality of apple-based products.

Finishing and polishing of composite resins

Em ordem sequencial, três diferentes etapas são utilizadas para finalizar a restauração de resina composta. Reanatomização, acabamento e polimento são procedimentos clínicos executados para obter melhor estética e longevidade de restaurações. O objetivo deste estudo foi avaliar o grau de rugosidade da superfície de três marcas de resinas compostas, submetidas a três técnicas de acabamento e polimento. 45 espécimes medindo 6 mm de diâmetro e 3 mm de espessura foram polimerizados sob uma matriz de poliéster com fotoativador LED da Microdont, com tempo de exposição de 20 segundos e divididos aleatoriamente em 4 grupos. Na aplicação das técnicas, foram usadas duas marcas de discos de lixa, sistema enhance e no grupo controle somente a matriz de poliéster. Após o tratamento da superfície, os espécimes foram avaliados em um rugosímetro e o parâmetro usado foi Ra, medida universalmente reconhecida. Os resultados revelaram a existência de diferenças significantes em ambas variáveis, ou seja, entre as resinas compostas e as técnicas empregadas. Os maiores valores de Ra em ordem decrescente de rugosidade foram Sprafill> Esthet-X> Filte> Z350 XT. As técnicas aplicadas não apresentaram uniformidades. As superfícies mais lisas foram obtidas com a matriz de poliéster, e nos espécimes tratados os melhores polimentos foram obtidos com os discos de lixa

In sequential order, three different steps are used to finish a composite resin restoration. Reanatomization, finishing and polishing are clinical procedures performed to obtain better esthetics and longevity of restorations. The objective of this study was to evaluate the degree of surface roughness of three brands of composite resin subjected to three different techniques of finishing and polishing. 45 specimens measuring 6 mm in diameter and 3 mm of thickness were polymerized in a polyester matrix with a Microdont LED Light Curing Unit, with an exposure time of 20 seconds, and divided randomly into 4 groups. In applying the techniques were used two brands of finishing discs, enhance system and as control group the polyester matrix only. After surface treatment, the roughness of the specimens was evaluated with Ra as universally recognized parameter. The results revealed the existence of significant differences in both variables, with other words, between the composite resins and the techniques employed. The highest values of Ra in roughness in descending order were Suprafill > Esthet–X > Filtek > Z350 XT. The applied techniques didn´t show any uniformity. The smoother surfaces were obtained with polyester matrix and in the treated specimens the best polishing were obtained with the finishing and polishing discs

Remodelação do tecido ósseo peri-implantar e apoptose / Peri-implantar bone tissue remodeling and apoptosis

O processo de remodelação óssea requer aaposição óssea por osteoblastos e a reabsorçãopor osteoclastos. Mecanismos de açãoinfluenciam o equilíbrio celular em contínua remodelaçãoóssea e grande parte das pesquisas direcionou-se para o estudo de fatores capazes de modularas funções. O normal processo de neoformação eadaptação óssea dependem do funcionamento deambos os tipos celulares. O osteoblasto é a célulamais importante nesse processo de reparação durantea osseointegração e o sucesso do tratamentodepende da sua adesão e proliferação. A maiorquota de responsabilidade da plasticidade do tecidoósseo cabe aos osteoclastos que respondema estímulos que promovem reabsorção da matrizinorgânica e liberação de componentes constituintes.Proteínas existentes no interior dososteoclastos atuam como mecanismo de inibiçãosobre as armas de autodestruição ouapoptose. Os processos de morte celular podemser classificados de acordo com suas característicasmorfológicas e bioquímicas em apoptose ou necrose.Na apoptose, não há o derramamento do conteúdocelular como ocorre na necrose e, por estarazão, não existe reação inflamatória.

The process of bone remodeling requires theaffixing by osteoblasts and bone resorptionby osteoclasts. Mechanisms of action influencethe cellular balance continuous remodelingand most of the research directed to thestudy of factors that modulate the functions.Normal process of neoformation and boneadaptation depends on the functioning ofboth cell types. The osteoblast cell is moreimportant in this repair process during osseointegrationand the success of treatmentdepends on the adhesion and proliferation.The largest share of the responsibility of theplasticity of bone tissue is up to osteoclastswhich respond to stimuli that promote reabsorptionof inorganic matrix and release ofcomponents constituents. Proteins withinthe existing osteoclasts act as a mechanismof inhibition on weapons of destruction orapoptosis. The processes of cell death can beclassified according to their morphologicaland biochemical characteristics: apoptosis ornecrosis. In apoptosis, there is no spillage ofthe contents as in cell necrosis and thereforethere is no inflammatory reaction.

Laboratory guidelines for animal care.

Animal research is a controversial subject because of the ethical and moral implications of using unwilling research subjects in potentially painful or distressful procedures usually ending in euthanasia. As such, it must be conducted in a compassionate and responsible manner geared toward maximizing the animals' quality of life prior to and during experimentation. Because of its contentious nature, the conduct of animal research is highly regulated at the federal, state, city, and institutional levels. It is essential that researchers acquire a working knowledge of the procedures and regulations in order to protect themselves and their staff from occupational hazards as well as protect their labs from criticism or attack from animal rights organizations. Perhaps the best way to protect from the latter is to avoid inadvertent instances of noncompliance with their research protocol or applicable regulations. Regulatory noncompliance can also have serious negative consequences on investigators' research ranging from temporary suspension of their protocols to loss of funding or principal investigator status. To minimize such events, it is advised that researchers build positive and collaborative relationships, trust and rapport with key institutional players, such as the veterinary staff, the Institutional Animal Care and Use Committee (IACUC), and top administrators. Guidance is provided regarding the appropriate handling of regulatory noncompliances.

Avaliação da auto-percepção de mulheres portadoras de fissuras orais / Evaluation the perception of itself of the oral cleft women

As fissuras orais são as anomalias craniofaciais congênitas mais comuns nos seres humanos e acarretam diversas alterações funcionais e estéticas para os portadores dessa anomalia. Desta forma, o presente trabalho tem o objetivo de avaliar como mulheres portadoras de FL/P percebem sua estética facial, bem como analisar as variáveis envolvidas com essa percepção. Foi realizado um exame clínico e um questionário com 22 pacientes do gênero feminino que estavam em tratamento no Centro de Tratamento de Anomalias Craniofaciais do Rio de Janeiro. A maioria das pacientes demonstrou algum nível de insatisfação com a aparência do seu rosto, sendo o nariz (n=9) e os dentes (n=5) a maior queixa relatada pelas pacientes. Os profissionais da área da saúde devem reabilitar as alterações faciais proporcionando estética e qualidade de vida.

The oral clefts are the most common congenital craniofacial anomalies in humans and lead various alterations for individuals with this anomaly. Thus, this study aimed to evaluate oral cleft women perception regading their facial aesthetics, and analyze the variables involved with that perception. We conducted a clinical examination and a questionnaire with 22 female patients Who were in a treatment at the Center for Treatment of Craniofacial Anomalies of Rio de Janeiro. Most patients showed some level of satisfaction with the appearance of their faces. The nose (n=9) and teeth (n=5) were the main complaint reported by patients. The health Professional teams must rehabilitate the facial changes providing aesthetic and quality of life.

Agenesia dental do incisivo lateral superior / Congenitally absent maxillary lateral incisors

A agenesia do incisivo lateral superior é definida como uma anomalia na arcada dentária dos seres humanos com bastante assiduidade. Como resultado da análise evidenciada pela tomada de radiografias da maxila e da mandíbula, pode-se relacionar que a ausência de dente unilateral prevalece significantemente sobre a agenesia bilateral. Do que foi observado, a ausência dos incisivos laterais pode trazer o desequilibro de oclusão e dentre das opções clínicas incluem de fechamento do espaço por tratamento ortodôntico com deslizamentos dos caninos, manutenção do espaço com posterior aplicação de próteses fixa ou adesivas, ou implantes osseointegrados unitários.

Mini-implantes ortodônticos / Orthodontic mini-implants

Os mini-implantes, confeccionados com titânio cp, apresenta baixa resistência e a possibilidade de fraturas durante os procedimentos de inserção e remoção. Assim, na maioria, é empregada a liga de Ti-6Al-4V, por sua maior resistência à fadiga e à fratura mas a desvantagem dessa liga é a sua menor resistência à corrosão favorecendo a liberação de íons metálicos. Como a tendência de liberação dos íons de metais é em quantidades extremamente baixas os mini-implantes ortodônticos de Ti-6Al-4V podem ser usados com segurança como dispositivos auxiliares de ancoragem ortodôntica. A forma cônica é a mais utilizada devido ao formato que permite a distribuição da carga funcional sem causar danos à fisiologia do tecido ósseo e tende a limitar ao máximo o trauma cirúrgico. Quanto maior quantidade de roscas, maior será a resistência ao deslocamento e a estabilidade primária. O mini-implante pode ser autorosqueante ou autoperfurante. O exame clínico constitui-se na palpação digital na região radicular e é muito importante, mas tomadas de radiografias panorâmicas e periapicais, são também importantes, pois auxiliam o profissional a identificar a anatomia, o local das raízes dos dentes e a densidade óssea, para a instalação dos mini-implantes. Representam uma diretriz clínica com a expectativa de selecionar a melhor posição, de acordo com ângulos diferentes da inserção, para a colocação do mini-implante no que diz respeito à espessura da proximidade cortical do osso e da raiz.

Comparing isoflurane with tribromoethanol anesthesia for echocardiographic phenotyping of transgenic mice.

Cardiac phenotyping of transgenic mice typically requires anesthesia. Chemical-grade tribromoethanol (TBE) is commonly used for this purpose due to its relatively short duration of action, modest cardiodepressive effects, and its noncontrolled status. In the present study, we used both genders of C57BL/6;C3H-Tg(Slc8a1)hKdp transgenic (TG) mice and C57BL/6;C3H wild-type (WT) mice to evaluate isoflurane (ISF) as a pharmaceutical-grade alternative to TBE for echocardiography and electrocardiography. Baseline target physiologic heart rates (beats per minute) were established by use of telemetry as 544 +/- 10 in WT mice and 580 +/- 21 in TG mice. TG and WT animals were anesthetized with either 0.8% to 1% inhalational ISF or 250 mg/kg intraperitoneal TBE. The following parameters were measured or calculated according to the previously defined physiologic heart rates: end diastolic and systolic dimensions; posterior wall and ventricular septal thicknesses; left ventricular mass, aortic ejection times; left ventricular fractional shortening; velocity of circumferential fiber shortening; and left ventricular ejection fraction. No significant difference between anesthetics was found for any measured cardiac parameters. However, the time required for data acquisition was significantly shorter for ISF (10 min) than for TBE (14 min). This study demonstrates that comparable echocardiographic results can be obtained at higher throughput by use of pharmaceuticalgrade ISF than with chemical-grade TBE.

Preclinical safety evaluation of 18F-FHBG: a PET reporter probe for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk) or mutant HSV1-sr39tk's expression.

UNLABELLED: 9-(4-(18)F-Fluoro-3-[hydroxymethyl]butyl)guanine ((18)F-FHBG) is a sensitive and specific PET reporter probe for imaging the PET reporter genes, herpes simplex 1 thymidine kinase (HSV1-tk) and its mutant HSV1-sr39tk. (18)F-FHBG has suitable pharmacokinetics and dosimetry for clinical applications and imaging of HSV1-TK has been demonstrated in the livers of hepatocellular cancer patients. METHODS: Male and female Sprague-Dawley rats and New Zealand White rabbits were divided into equal groups receiving either 14 microg/kg cold FHBG or carrier solution, for a 14-d acute toxicity assessment. We monitored body weight, food and water consumption, body temperature, cardiovascular electrical and functional indices, respiratory performance and oxygen saturation, comprehensive blood chemistry, complete blood count (CBC), and urinalysis. We conducted daily cage-side examinations for the detection of any clinical abnormalities. Tissues of the animals that were euthanized and necropsied on day 14 were prepared for histopathologic examination. RESULTS: No significant differences in cardiovascular and respiratory parameters, food consumption, body weight, urine components, or clinical signs attributable to test article toxicity were observed between the treatment and control groups. Any differences noted in the blood chemistry and CBC parameters were deemed to be incidental findings unrelated to the administration of the FHBG. CONCLUSION: Acute toxicity evaluation of FHBG at 100 times the expected human dose does not indicate harm to organ function or tissues. The Food and Drug Administration has approved FHBG as an Investigational New Drug.