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1.
Artigo em Inglês | MEDLINE | ID: mdl-38979844

RESUMO

There are no published reports describing the anatomic variations of the phrenicoabdominal (PhAbd) veins in cats. The aim of this study was to evaluate the anatomic variations of the PhAbd veins in cats without adrenal disease. This is an anatomic study. Abdominal CT images of cats acquired from January 2021 to February 2023 were retrospectively reviewed. Inclusion criteria were the presence of pre- and postcontrast CT images of the abdomen and the absence of any abdominal diseases that compromise the left and right PhAbd veins visualization. A total of 128 cats were included. Three different vascular anatomic variations were found in the distal pericaval segment of the left phrenicoabdominal (LPhAbd) vein. In the first type, found in 65 cases (50.8%), the LPhAbd vein drained directly into the caudal vena cava. In the second type defined IIa, found in 25 cases (19.5%), the LPhAbd vein drained into the distal third of the left renal vein, less than 5 mm from its opening into the caudal vena cava. In the third type defined IIb, found in 38 cases (29.7%), the LPhAbd vein drained into the distal third of the left renal vein, more than 5 mm from its opening into the caudal vena cava. The right phrenicoabdominal vein had a consistent path and drained into the caudal vena cava in all cases. The knowledge of these vascular variations is expected to help the surgeon during adrenalectomy due to masses with vascular invasion in cats.

2.
Vet Sci ; 10(8)2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37624314

RESUMO

Equine asthma is a common respiratory disease that may affect horses of any age. The diagnosis of severe equine asthma (SEA) (historically referred as recurrent airway obstruction or RAO) is based mainly on the history of the animal and clinical signs, which are further supported by the cytological examination of the bronchoalveolar lavage (BAL). This can also be helpful in monitoring the inflammation of the lower airways in response to environmental management and medication. The cytocentrifugated preparation is usually considered the method of choice for BAL cytological interpretation. The aim of this study was to compare the results in terms of differential cell counts (DCC) in BAL cytology performed on sedimented smears and cytocentrifugated preparations. To carry this out, 48 BAL samples were collected from six horses with SEA that were subjected to a process of exacerbation of the disease by environmental stimuli, which was later followed by the appropriate treatment. Each collected BAL fluid was equally divided into duplicate portions: one processed by cytocentrifugation and one by sediment smear from simple centrifugation. Cytologic examination of all BAL by both methods showed poor concordance in DCC, although it was still able to allow diagnostic recognition of severe lung neutrophilic disorders. These results suggest that sediment smear preparation, although remaining a useful method in general equine practice associated with clinical assessments in the diagnosis of SEA under conditions where there is no possibility of using a cytocentrifuge, cannot be considered a comparable alternative.

3.
J Med Chem ; 62(10): 5049-5062, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31050898

RESUMO

The first generation of CB1 positive allosteric modulators (e.g., ZCZ011) featured a 3-nitroalkyl-2-phenyl-indole structure. Although a small number of drugs include the nitro group, it is generally not regarded as being "drug-like", and this is particularly true for aliphatic nitro groups. There are very few case studies where an appropriate bioisostere replaced a nitro group that had a direct role in binding. This may be indicative of the difficulty of replicating its binding interactions. Herein, we report the design and synthesis of ligands targeting the allosteric binding site on the CB1 cannabinoid receptor, in which a CF3 group successfully replaced the aliphatic NO2. In general, the CF3-bearing compounds were more potent than their NO2 equivalents and also showed improved in vitro metabolic stability. The CF3 analogue (1) with the best balance of properties was selected for further pharmacological evaluation. Pilot in vivo studies showed that (±)-1 has similar activity to (±)-ZCZ011, with both showing promising efficacy in a mouse model of neuropathic pain.


Assuntos
Nitrocompostos/síntese química , Nitrocompostos/farmacologia , Receptor CB1 de Canabinoide/efeitos dos fármacos , Regulação Alostérica/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Sítios de Ligação , AMP Cíclico/metabolismo , Desenho de Fármacos , Isomerismo , Ligantes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Moleculares , Neuralgia/tratamento farmacológico , Neuralgia/psicologia , Nitrocompostos/farmacocinética , Bibliotecas de Moléculas Pequenas , Relação Estrutura-Atividade
4.
Org Biomol Chem ; 15(22): 4907-4920, 2017 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-28548149

RESUMO

The synthesis of a small collection of novel bile acid-bisphosphonate (BA-BP) conjugates as potential drug candidates is reported. The disclosed methodology relied on the installation of azide and thiol functionalities at the head and tail positions, respectively, of the BA scaffold and its subsequent decoration by orthogonal click reactions (copper-catalyzed azide-alkyne cycloaddition, thiol-ene or thiol-yne coupling) to introduce BP units and a fluorophore. Because of the troublesome isolation of the target conjugates by standard procedures, the methodology culminated with the functionalization of the BA scaffold with a light fluorous tag to rapidly and efficiently purify intermediates and final products by fluorous solid-phase extraction.


Assuntos
Ácidos e Sais Biliares/farmacologia , Reabsorção Óssea/tratamento farmacológico , Difosfonatos/farmacologia , Corantes Fluorescentes/química , Ácidos e Sais Biliares/química , Química Click , Difosfonatos/química , Desenho de Fármacos , Corantes Fluorescentes/isolamento & purificação , Conformação Molecular , Extração em Fase Sólida
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