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1.
PLoS One ; 12(5): e0177910, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28542310

RESUMO

The parasitic nematode Angiostrongylus cantonensis is a major cause of eosinophilic meningitis in humans, and has been documented in other incidental hosts such as birds, horses, dogs and non-human primates. It is endemic in Hawaii, and there have been sporadic reports in the southern continental United States. This parasite uses rats as definitive hosts and snails as intermediate hosts. In this study, we collected potential definitive and intermediate hosts throughout Florida to ascertain the geographic distribution in the state: Rats, environmental rat fecal samples, and snails were collected from 18 counties throughout the state. Classical diagnostics and morphological identification, along with molecular techniques were used to identify nematode species and confirm the presence of A. cantonensis. Of the 171 Rattus rattus collected, 39 (22.8%) were positive for A. cantonensis, and 6 of the 37 (16.2%) environmental rat fecal samples collected in three of the surveyed counties were also positive for this parasite by real time PCR. We examined 1,437 gastropods, which represented 32 species; 27 (1.9%) were positive for A. cantonensis from multiple sites across Florida. Three non-native gastropod species, Bradybaena similaris, Zachrysia provisoria, and Paropeas achatinaceum, and three native gastropod species, Succinea floridana, Ventridens demissus, and Zonitoides arboreus, which are newly recorded intermediate hosts for the parasite, were positive for A. cantonensis. This study indicates that A. cantonensis is established in Florida through the finding of adult and larval stages in definitive and intermediate hosts, respectively, throughout the state. The ability for this historically subtropical nematode to thrive in a more temperate climate is alarming, however as the climate changes and average temperatures rise, gastropod distributions will probably expand, leading to the spread of this parasite in more temperate areas. Through greater awareness of host species and prevalence of A. cantonensis in the United States, potential accidental infections may be avoided.


Assuntos
Angiostrongylus cantonensis/fisiologia , Geografia , Caramujos/parasitologia , Animais , Florida , Interações Hospedeiro-Parasita , Ratos
2.
Vet Dermatol ; 28(2): 246-e65, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28133821

RESUMO

BACKGROUND: Mycosis fungoides (MF) is an uncommon cutaneous neoplasm in dogs. Treatment options are limited. Total skin electron therapy (TSET) has been suggested as a possible therapy for canine MF. OBJECTIVE: To describe the use of TSET as palliative treatment for MF in a dog. RESULTS: An adult dog, previously diagnosed with nonepidermolytic ichthyosis, was presented with generalized erythroderma, alopecia and erosions. Histopathology revealed a densely cellular, well-demarcated, unencapsulated infiltrate extending from the epidermis to the mid-dermis compatible with MF. The infiltrate exhibited epitheliotropism multifocally for the epidermis, infundibula and adnexa. Due to a lack of response to chemotherapy, TSET was elected. Six megavoltage electrons were delivered using a 21EX Varian linear accelerator. A dose of 6 Gy was delivered to the skin surface and a 100 cm skin to surface distance was used for dog setup. The treatment time for the cranial half treatment was 3 h. The treatment was divided in two sessions (cranial and caudal halves of the body) 15 days apart. Clinical and histopathological complete remission was achieved and the dog was kept in remission with no additional treatments for 19 months before relapse and development of Sézary syndrome. CONCLUSION AND CLINICAL SIGNIFICANCE: To the best of the authors' knowledge, this is the first case reporting the use of TSET for medically refractory canine MF with post treatment follow-up. This case suggests that the use of TSET may be an effective palliative treatment for canine MF.


Assuntos
Doenças do Cão/terapia , Micose Fungoide/veterinária , Neoplasias Cutâneas/veterinária , Irradiação Corporal Total/veterinária , Animais , Doenças do Cão/radioterapia , Cães , Evolução Fatal , Feminino , Micose Fungoide/patologia , Micose Fungoide/radioterapia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/radioterapia
3.
J Vet Diagn Invest ; 29(1): 51-58, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27852812

RESUMO

Fungi in the genus Aspergillus are some of the most common fungal pathogens in veterinary species, primarily affecting the respiratory tract. In both human and veterinary cases, calcium oxalate crystals have been documented in sites of Aspergillus infection. Cases in multiple species (16 birds, 15 horses, 5 dogs, 1 ox, and 1 dolphin) were identified that had either positive cultures for Aspergillus sp., or had conidiophores present that could be identified as belonging to the genus Aspergillus. Histologic slides were examined to confirm the presence of oxalate crystals and how often they were identified on the original report. Calcium oxalate deposition was detected in 14 of 38 cases examined, including A. fumigatus, A. versicolor, A. niger, and unspecified Aspergillus sp. infections. Calcium oxalate crystals were identified in 11 of 16 avian cases, as well as in 1 of 1 bovine, 1 of 15 equine, and 1 of 5 canine cases. Crystals were described in only 3 of the 14 original pathology reports of these cases, indicating that identification and reporting of crystals in histologic specimens could be improved. All the tissues with crystals were respiratory tissues with air interfaces, including nasal sinus, trachea, syrinx, lung, and air sac. In cases with crystals identified on H&E-stained sections, crystals were frequently not present or were fewer in number in tissue sections stained with Gomori methenamine silver and periodic acid-Schiff. Routine polarization of slides of fungal infections, especially in the respiratory tract, should be considered to check for calcium oxalate crystals.


Assuntos
Aspergilose/veterinária , Aspergillus niger/isolamento & purificação , Oxalato de Cálcio/análise , Pneumopatias Fúngicas/veterinária , Animais , Aspergilose/diagnóstico , Aspergilose/patologia , Aves , Bovinos , Cães , Golfinhos , Cavalos , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/patologia , Prevalência , Estudos Retrospectivos , Coloração e Rotulagem/veterinária
4.
Vet Ophthalmol ; 19(4): 332-339, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26215738

RESUMO

A 1-day-old miniature horse filly was presented to the University of Florida Veterinary Ophthalmology service for evaluation of multiple ocular anomalies which were present from birth. Protruding from the right orbit was a large, fluctuant, red, dry and variably ulcerated mass. A globe could not be appreciated clinically in the left orbit. Ocular ultrasound of both orbits was performed. This revealed a lobular, hypo-echoic structure filling the right orbit, with multiple hyperechoic septations; normal ocular structures were not identified. Ultrasound of the left orbit revealed a microphthalmic eye, with a well-defined, hyperechoic structure in the vitreous that was thought to be the lens. Due to irreversible blindness, the foal was humanely euthanized. Histopathology and immunohistochemistry of the orbital contents revealed bilateral microphthalmos with cyst, a congenital defect rarely reported in the veterinary literature.

5.
BMC Pediatr ; 15: 8, 2015 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-25884320

RESUMO

BACKGROUND: Surgical correction of orofacial clefts greatly mitigates negative outcomes. However, access to reconstructive surgery is limited in developing countries. The present study reviews epidemiological data from a single charitable organization, Smile Train, with a database of surgical cases from 33 African countries from 2001-2011. METHODS: Demographic and clinical patient data were collected from questionnaires completed by the participating surgeons. These data were recorded in Excel, analyzed using SPSS and compared with previously reported data. RESULTS: Questionnaires were completed for 36,384 patients by 389 African surgeons. The distribution of clefts was: 34.44% clefts of the lip (CL), 58.87% clefts of the lip and palate (CLP), and 6.69% clefts of the palate only (CP). The male to female ratio was 1.46:1, and the unilateral: bilateral ratio 2.93:1, with left-sided predominance 1.69:1. Associated anomalies were found in 4.18% of patients. The most frequent surgeries included primary lip/nose repairs, unilateral (68.36%) and bilateral (11.84%). There was seasonal variation in the frequency of oral cleft births with the highest in January and lowest by December. The average age at surgery was 9.34 years and increased in countries with lower gross domestic products. The average hospital stay was 4.5 days. The reported complication rate was 1.92%. CONCLUSIONS: With the exception of cleft palates, results follow trends of worldwide epidemiologic reports of 25% CL, 50% CLP, and 25% CP, 2:1 unilateral:bilateral and left:right ratios, and male predominance. Fewer than expected patients, especially females, presented with isolated cleft palates, suggesting that limitations in economic resources and cultural aesthetics of the obvious lip deformity may outweigh functional concerns and access to treatment for females. A fewer than expected associated anomalies suggests either true ethnic variation, or that more severely-affected patients are not presenting for treatment. The epidemiology of orofacial clefting in Africa has been difficult to assess due to the diversity of the continent and the considerable variation among study designs. The large sample size of the data collected provides a basis for further study of the epidemiology of orofacial clefting in Africa.


Assuntos
Fenda Labial/epidemiologia , Fenda Labial/cirurgia , Fissura Palatina/epidemiologia , Fissura Palatina/cirurgia , Procedimentos de Cirurgia Plástica , Anormalidades Múltiplas/epidemiologia , Anormalidades Múltiplas/cirurgia , África/epidemiologia , Criança , Pré-Escolar , Países em Desenvolvimento , Feminino , Humanos , Masculino , Procedimentos de Cirurgia Plástica/efeitos adversos , Estudos Retrospectivos , Estações do Ano , Distribuição por Sexo , Inquéritos e Questionários
6.
Vet Ophthalmol ; 18(6): 515-20, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25728848

RESUMO

CASE DESCRIPTION: A 5.5-year-old neutered male mixed-breed dog was presented for evaluation of a 5-month history of deviation of the right globe upon opening the mouth and a 1-month history of conjunctivitis in the same eye. Clinical findings, diagnostic imaging results, treatment and follow-up are described. CLINICAL FINDINGS: When the mouth was opened, the right globe deviated rostrally and laterally. There was no pain or resistance to opening the mouth, or resistance to retropulsion of the globe. No other abnormalities were observed. Computed tomography was performed, revealing a contrast-enhancing region associated with the right masseter muscle impinging into the right orbit; this was more pronounced with the mouth open. Cytology revealed a small number of mildly to moderately atypical mesenchymal cells. Histopathology was consistent with polyphasic myositis, with a predominance of lymphocytes and plasma cells. No infectious agents were identified. Serum antibody titers for Toxoplasma gondii and Neospora caninum were negative. Serum titers for 2 M antibody were positive at 1:500, consistent with a diagnosis of masticatory muscle myositis. TREATMENT AND OUTCOME: Therapy with prednisone was initiated. During a follow-up period of 5 months, there was no recurrence of clinical signs, and the dose of prednisone was reduced by 25%. CLINICAL SIGNIFICANCE: To the authors' knowledge, this is the first reported case of masticatory muscle myositis causing dynamic exophthalmos and strabismus in a dog.


Assuntos
Doenças do Cão/diagnóstico , Exoftalmia/veterinária , Músculos da Mastigação , Miosite/veterinária , Estrabismo/veterinária , Animais , Anti-Inflamatórios/uso terapêutico , Doenças do Cão/etiologia , Doenças do Cão/patologia , Cães , Exoftalmia/diagnóstico , Exoftalmia/etiologia , Exoftalmia/patologia , Masculino , Miosite/complicações , Miosite/diagnóstico , Miosite/tratamento farmacológico , Prednisona/uso terapêutico , Estrabismo/diagnóstico , Estrabismo/etiologia , Estrabismo/patologia
7.
J Craniofac Surg ; 25(5): 1601-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25072973

RESUMO

BACKGROUND: A charitable surgical relief organization (Smile Train) enables local physicians in developing countries to provide surgical treatment of cleft lip and/or palate. The following study reviews the epidemiological data from more than 260,000 surgeries performed in India through this organization from 2000 until January 1, 2012. METHODS: Demographic and clinical patient data were collected from the participating surgeons, recorded in Excel (Microsoft, Redmond, WA), and analyzed using Software Package for the Social Sciences (IBM, Armonk, NY). RESULTS: The distribution of clefts treated was 20.2% of cleft lip, 13.9% of cleft palate (CP), and 65.9% of cleft lip and palate. The overall unilateral-bilateral ratio was 2.49:1 with a left-right ratio of 2.03:1. The male-female ratio was 1.58:1. Of the total patients, 2.67% had associated anomalies. The most frequently performed surgeries included primary repair of a unilateral cleft lip (41.62%), followed by primary repair of a CP (31.15%). The mean age at surgery was 7.91 years. The reported complication rate was 0.88%. CONCLUSIONS: The data collected are from the largest reported cohort of orofacial cleft patients in India. The cleft type, sex distribution, and overall male predominance resemble previously reported distributions; however, fewer CP patients and greater cleft lip and palate patients presented than would be expected. The frequency of associated anomalies was lower than in previous reports. Although there is significant selection bias to milder cases from lower socioeconomic groups in this study, the large sample size is unique, and the data collected can provide a valuable framework to further study the epidemiology of cleft lip and/or palate in India.


Assuntos
Fenda Labial/epidemiologia , Fissura Palatina/epidemiologia , Procedimentos de Cirurgia Plástica/estatística & dados numéricos , Distribuição por Idade , Criança , Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Feminino , Humanos , Índia/epidemiologia , Masculino , Complicações Pós-Operatórias , Estudos Retrospectivos , Distribuição por Sexo
8.
PeerJ ; 2: e377, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24860702

RESUMO

Histopathology is the most useful tool for diagnosis of a number of diseases, especially cancer. To be effective, histopathology requires that tissues be fixed prior to processing. Formalin is currently the most common histologic fixative, offering many advantages: it is cheap, readily available, and pathologists are routinely trained to examine tissues fixed in formalin. However, formalin fixation substantially degrades tissue DNA, hindering subsequent use in diagnostics and research. We therefore evaluated three alternative fixatives, TissueTek(®) Xpress(®) Molecular Fixative, modified methacarn, and PAXgene(®), all of which have been proposed as formalin alternatives, to determine their suitability for routine use in a veterinary diagnostic laboratory. This was accomplished by examining the histomorphology of sections produced from fixed tissues as well as the ability to amplify fragments from extracted DNA. Tissues were sampled from two dogs and four cats, fixed for 24-48 h, and processed routinely. While all fixatives produced acceptable histomorphology, formalin had significantly better morphologic characteristics than the other three fixatives. Alternative fixatives generally had better DNA amplification than formalin, although results varied somewhat depending on the tissue examined. While no fixative is yet ready to replace formalin, the alternative fixatives examined may be useful as adjuncts to formalin in diagnostic practices.

9.
J Am Vet Med Assoc ; 244(3): 346-51, 2014 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-24432967

RESUMO

CASE DESCRIPTION: A 10-year-old spayed female Jack Russell Terrier and a 7-year-old neutered male mixed-breed dog were evaluated because of acute, progressive, unilateral forelimb lameness associated with signs of pain and turgid antebrachial swelling. CLINICAL FINDINGS: For either dog, there were no salient pathological or diagnostic imaging abnormalities. A diagnosis of compartment syndrome was confirmed on the basis of high caudal antebrachial compartmental pressure in the affected forelimb. TREATMENT AND OUTCOME: Both dogs underwent surgical exploration of the affected forelimb. In each case, an intramuscular tumor (mast cell tumor in the Jack Russell Terrier and suspected sarcoma in the mixed-breed dog) was detected and presumed to be the cause of the high compartmental pressure. At 6 months following tumor excision, the dog with the mast cell tumor did not have any clinical signs of disease. The dog with a suspected sarcoma underwent tumor excision and forelimb amputation at the proximal portion of the humerus followed by chemotherapy; the dog was euthanized approximately 1 year following treatment because of pulmonary metastasis. CLINICAL RELEVANCE: Compartment syndrome is a serious but rarely reported condition in dogs and is typically ascribed to intracompartmental hemorrhage. These 2 cases illustrate the potential for expansile intramuscular antebrachial tumors to cause compartment syndrome in dogs.


Assuntos
Síndromes Compartimentais/veterinária , Doenças do Cão/etiologia , Mastocitoma/veterinária , Sarcoma/veterinária , Animais , Síndromes Compartimentais/etiologia , Síndromes Compartimentais/cirurgia , Doenças do Cão/patologia , Cães , Feminino , Masculino , Mastocitoma/complicações , Mastocitoma/cirurgia , Sarcoma/complicações , Sarcoma/cirurgia
10.
J Zoo Wildl Med ; 44(3): 744-8, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24063105

RESUMO

An adult male pygmy sperm whale (Kogia breviceps) was stranded within a tidal pool on Fernandina Beach on the north Florida Atlantic coast (USA) and expired soon after discovery. Necropsy findings included a small intestinal mass markedly expanding the intestinal wall and partially obstructing the lumen. This finding likely led to the malnutrition and ultimately the stranding of this whale. The differential diagnoses for the mass based on gross evaluation included a duodenal adenocarcinoma, leiomyoma/sarcoma, gastrointestinal stroma tumor, and benign/malignant peripheral nerve sheath tumor, previously referred to as neurofibromas or schwannomas. The mass was presumptively diagnosed as a leiomyosarcoma via routine histopathology and confirmed by immunoreactivity for desmin and smooth actin (SMA). KIT, a gene name for CD 117, was negative, excluding a gastrointestinal stromal tumor (GIST). Leiomyosarcomas have been reported within numerous wild and domestic species, although this is the first reported case of any neoplasm in a pygmy sperm whale (K. breviceps).


Assuntos
Neoplasias Intestinais/veterinária , Intestino Delgado/patologia , Leiomiossarcoma/veterinária , Baleias , Animais , Evolução Fatal , Neoplasias Intestinais/patologia , Leiomiossarcoma/patologia , Masculino
11.
J Vet Diagn Invest ; 25(3): 433-7, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23628640

RESUMO

A novel gammaherpesvirus was identified in a large flying fox (Pteropus vampyrus) with conjunctivitis, blepharitis, and meibomianitis by nested polymerase chain reaction and sequencing. Polymerase chain reaction amplification and sequencing of 472 base pairs of the DNA-dependent DNA polymerase gene were used to identify a novel herpesvirus. Bayesian and maximum likelihood phylogenetic analyses indicated that the virus is a member of the genus Percavirus in the subfamily Gammaherpesvirinae. Additional research is needed regarding the association of this virus with conjunctivitis and other ocular pathology. This virus may be useful as a biomarker of stress and may be a useful model of virus recrudescence in Pteropus spp.


Assuntos
Blefarite/veterinária , Quirópteros , Gammaherpesvirinae/isolamento & purificação , Infecções por Herpesviridae/veterinária , Animais , Blefarite/virologia , Gammaherpesvirinae/classificação , Infecções por Herpesviridae/virologia , Masculino , Filogenia
12.
J Am Anim Hosp Assoc ; 49(4): 286-92, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23690488

RESUMO

A severe increase in total bilirubin coincided with a decline in neurologic status to comatose in a 9 yr old spayed female mixed-breed dog being treated for immune-mediated hemolytic anemia. MRI of the brain was performed to investigate potential causes for the neurologic signs. MRI revealed bilaterally symmetrical hyperintensities within the caudate nuclei, globus pallidus, thalamus, deep cerebellar nuclei, and cortical gray matter on T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequences, which coincided with areas of bilirubin deposition and neuronal necrosis (kernicterus) identified on necropsy examination. This is the second case report of an adult dog exhibiting kernicterus, and the first report to document MRI findings associated with that condition. Kernicterus is an uncommonly reported complication of hyperbilirubinemia in dogs, but is potentially underreported due to difficulties in recognizing subtle lesions and distinguishing kernicterus from other potential causes of neurologic abnormalities with readily available antemortem tests. MRI may be helpful in supporting the diagnosis of kernicterus.


Assuntos
Doenças do Cão/diagnóstico , Doenças do Cão/etiologia , Hiperbilirrubinemia/veterinária , Kernicterus/veterinária , Imageamento por Ressonância Magnética/veterinária , Animais , Encéfalo/patologia , Doenças do Cão/patologia , Cães , Evolução Fatal , Feminino , Hiperbilirrubinemia/complicações , Hiperbilirrubinemia/diagnóstico , Kernicterus/diagnóstico , Kernicterus/etiologia , Kernicterus/patologia
13.
J Am Anim Hosp Assoc ; 48(3): 198-202, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22474048

RESUMO

A 2 yr old dog presented for dysphagia and coughing secondary to a 4 cm × 4 cm turgid subepiglottic mass. Cervical radiographs, an esophagram, and computed tomography confirmed the presence of a cystic mass that was not intimately associated with any surrounding structures. An incisional biopsy confirmed the cystic nature of the mass and helped to rule out a malignancy. A marginal surgical excision was performed via a ventral approach. Histopathology of the mass was consistent with a thyroglossal duct cyst. This is the first report of a thyroglossal duct cyst in this location in a dog. There was no recurrence of clinical signs 14 mo after surgery.


Assuntos
Doenças do Cão/cirurgia , Cisto Tireoglosso/veterinária , Animais , Cães , Masculino , Cisto Tireoglosso/cirurgia , Resultado do Tratamento
15.
J Vet Med Sci ; 74(7): 945-7, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22446393

RESUMO

A 5-day-old Huacaya alpaca cria (Vicugna pacos) was euthanized due to deteriorating health. At birth, the cria had ophthalmologic abnormalities, but had appropriate mentation. At 2 days of age, the cria gradually stopped suckling and began to circle. At 5 days old, the owner elected euthanasia due to declining clinical condition. Grossly, the right iris had a scalloped pupillary margin, and the right olfactory bulb was malformed. Histopathology revealed persistent hyperplastic primary vitreous bilaterally and iridal abnormalities, as well as aplasia of the olfactory ventricle, olfactory tract, and olfactory foramen on the right side.


Assuntos
Animais Recém-Nascidos , Camelídeos Americanos/anormalidades , Prosencéfalo/anormalidades , Animais , Evolução Fatal , Feminino , Técnicas Histológicas/veterinária , Iris/anormalidades , Bulbo Olfatório/anormalidades , Condutos Olfatórios/anormalidades
16.
Vet Ophthalmol ; 15(5): 351-4, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22348259

RESUMO

An 8-year-old Gypsy Vanner gelding presented to the University of Florida Ophthalmology service for the evaluation of chronic, recurrent corneal ulcers behind the third eyelid of the right eye. On ophthalmic examination, a cluster of aberrant hairs was identified growing along the margin of the third eyelid. This portion of third eyelid was surgically excised, and histopathology identified the haired tissue as a dermoid. Chronic keratitis secondary to a third eyelid dermoid was diagnosed, and excision appeared curative at 6 months post-operative follow-up.


Assuntos
Cisto Dermoide/veterinária , Neoplasias Palpebrais/veterinária , Doenças dos Cavalos/patologia , Membrana Nictitante/patologia , Animais , Cisto Dermoide/patologia , Cisto Dermoide/cirurgia , Neoplasias Palpebrais/patologia , Neoplasias Palpebrais/cirurgia , Doenças dos Cavalos/cirurgia , Cavalos , Masculino , Membrana Nictitante/cirurgia
17.
Dalton Trans ; 40(2): 337-9, 2011 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-21079864

RESUMO

Chromium(III) mesityl complexes were synthesized by protonolysis of chromocene with 1,3-diisopropylimidazolium chloride or DBU hydrochloride, salt metathesis with MesMgBr, and single electron oxidation with iodine.

18.
J Am Chem Soc ; 132(48): 17325-34, 2010 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-21070039

RESUMO

A range of paramagnetic Cr(III) monohydrocarbyl complexes CpCr[(ArNCMe)2CH](R) (Ar = ortho-disubstituted aryl; R = primary alkyl, trimethylsilylmethyl, benzyl, phenyl, alkenyl, or alkynyl) were synthesized to investigate how varying the steric and electronic properties of the R group affected their propensity for Cr-R bond homolysis. Most complexes were prepared by salt metathesis of known CpCr[(ArNCMe)2CH](Cl) compounds in Et2O with commercial RMgCl solutions, although more sterically demanding combinations of Ar and R groups necessitated the use of halide-free MgR2 reagents and the Cr(III) tosylate or triflate derivatives. Alternative synthetic routes to Cr(III)-R species using the previously reported Cr(II) compounds CpCr[(ArNCMe)2CH] and sources of R· radicals (e.g., BEt3 and air) were also explored. The UV-vis spectra of the CpCr[(ArNCMe)2CH](R) complexes possessed two strong bands with maximum absorbances in the ranges 395-436 nm and 535-582 nm, with the band in the latter range being particularly characteristic of the Cr(III)-R compounds. The Cr-CH2R bond lengths as determined by single-crystal X-ray diffraction were longer than those in the corresponding Cr-CH3 complexes, typically falling in the range 2.10 to 2.13 Å. The Cr(III) benzyl compounds displayed longer Cr-CH2Ph distances, while the bond lengths for the alkenyl and alkynyl species were substantially shorter. The rate of Cr-R bond homolysis at room temperature was determined by monitoring the reaction of Cr(III) neopentyl, benzyl, and isobutyl complexes with excess PhSSPh using UV-vis spectroscopy. Although the other primary alkyl, phenyl, and alkenyl compounds did not undergo appreciable homolysis under these conditions, they were cleanly converted to CpCr[(ArNCMe)2CH](SPh) by photolysis.

19.
Nat Biotechnol ; 28(1): 79-82, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20037580

RESUMO

Reengineering the receptor footprints of adeno-associated virus (AAV) isolates may yield variants with improved properties for clinical applications. We generated a panel of synthetic AAV2 vectors by replacing a hexapeptide sequence in a previously identified heparan sulfate receptor footprint with corresponding residues from other AAV strains. This approach yielded several chimeric capsids displaying systemic tropism after intravenous administration in mice. Of particular interest, an AAV2/AAV8 chimera designated AAV2i8 displayed an altered antigenic profile, readily traversed the blood vasculature, and selectively transduced cardiac and whole-body skeletal muscle tissues with high efficiency. Unlike other AAV serotypes, which are preferentially sequestered in the liver, AAV2i8 showed markedly reduced hepatic tropism. These features of AAV2i8 suggest that it is well suited to translational studies in gene therapy of musculoskeletal disorders.


Assuntos
Dependovirus/genética , Técnicas de Transferência de Genes , Engenharia Genética , Músculos/metabolismo , Receptores Virais/genética , Animais , Dependovirus/fisiologia , Vetores Genéticos/sangue , Camundongos , Modelos Moleculares , Músculos/virologia , Especificidade de Órgãos , Relação Estrutura-Atividade , Tropismo Viral
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