High-Throughput Compound Quality Assessment with High-Mass-Resolution Acoustic Ejection Mass Spectrometry: An Automatic Data Processing Toolkit.

Pharmacological screening heavily relies on the reliability of compound libraries. To ensure the accuracy of screening results, fast and reliable quality control (QC) of these libraries is essential. While liquid chromatography (LC) with ultraviolet (UV) or mass spectrometry (MS) detection has been employed for molecule QC on small sample sets, the analytical throughput becomes a bottleneck when dealing with large libraries. Acoustic ejection mass spectrometry (AEMS) is a high-throughput analytical platform that covers a broad range of chemical structural space. In this study, we present the utilization of an AEMS system equipped with a high-resolution MS analyzer for high-throughput compound QC. To facilitate efficient data processing, which is a key challenge for such a high-throughput application, we introduce an automatic data processing toolkit that allows for the high-throughput assessment of the sample standards' quantitative and qualitative characteristics, including purity calculation with the background processing option. Moreover, the toolkit includes a module for quantitatively comparing spectral similarity with the reference library. Integrating the described high-resolution AEMS system with the data processing toolkit effectively eliminates the analytical bottleneck, enabling a rapid and reliable compound quality assessment of large-scale compound libraries.

Segmental hypoplasia of the spinal cord and syringomyelia in a calf / Hipoplasia segmentar de medula espinhal e siringomielia em um bezerro

ABSTRACT: Congenital malformations are functional and structural changes in organ systems, tissues, or organs that may develop during the embryonic or fetal phase. Spinal cord malformations, such as segmental hypoplasia of the spinal cord (SHSC) and syringomyelia, are rare in bovines. A Girolando calf from Valença, Rio de Janeiro, was admitted to the Veterinary Hospital of Universidade Federal Rural do Rio de Janeiro because of motor incoordination. Clinical evaluation revealed a 5-cm depression area in the spine at the dorsal line of the thoracic region. Neurological examination revealed reduced proprioception, pelvic limb extension with increased nociceptive activity, and reduced anal reflex. In radiographic examination, the body of the T11 vertebra had a trapezoidal wedge shape with ventral hemivertebra, probable agenesis or hypoplasia of the T11-T12 spinous processes, and fusion of the T9-T10 spinous processes. Myelography revealed extradural spinal compression caused by vertebral malformations. Necropsy showed no spinous processes (T11-T12), cranial stenosis in the medullary canal (T11-T13), and 1-3-mm pores in the white matter of the thoracic spinal cord (T8-T11). Microscopy revealed cystic dilatations in the white matter (T9-T11), cystic areas of varying sizes (T8-T9), and moderate reduction in the gray matter around the central canal of the medulla (T11-T13). Here, we reported the clinical and pathological findings of SHSC and syringomyelia in a Girolando calf. The features should be differentiated from other spinal cord syndromes. Congenital malformations are of economic importance, and their etiology and diagnosis are fundamental to disease control and progenitor-selection programs.

RESUMO: Malformações congênitas são alterações funcionais e estruturais dos sistemas, tecidos ou órgãos que podem ocorrer na fase embrionária ou fetal. Malformações na medula espinhal, como hipoplasia segmentar da medula espinhal (HSME) e siringomielia, possuem raras descrições em bovinos. Uma bezerra Girolando, proveniente do Município de Valença, RJ, foi atendida no Hospital Veterinário da Universidade Federal Rural do Rio de Janeiro (UFRRJ), com quadro de incoordenação motora. À avaliação clínica, na coluna vertebral, à linha dorsal da região torácica havia uma área com depressão de 5 cm. Ao exame neurológico foi observado propriocepção reduzida, extensão de membros pélvicos com aumento da atividade nociceptiva e redução de reflexo anal. Ao exame radiográfico, o corpo vertebral T11 apresentou forma trapezoidal em cunha com hemivértebra ventral, provável agenesia ou hipoplasia dos processos espinhosos T11-T12 e fusão dos processos espinhosos T9-T10. À mielografia indicou compressão medular extradural provocada pelas malformações vertebrais. À necropsia não foram observados os processos espinhosos T11-T12, o canal medular apresentou estenose cranial (T11-T13) e, na medula espinhal torácica (T8-T11) foram observados poros de 1-3 mm na substância branca. À microscopia, os segmentos T9-T11 apresentaram dilatações císticas na substância branca e os segmentos T8-T9, formações de áreas císticas de tamanhos variados; nos segmentos T11-T13 denotou-se moderada redução da substância cinzenta ao redor do canal central da medula. O presente trabalho tem o objetivo de apresentar os achados clínicos e patológicos desta bezerra Girolando com HSME e siringomielia, que devem ser diferenciadas de outras síndromes da medula espinhal. As malformações congênitas possuem importância econômica e sua etiologia e diagnóstico são fundamentais para a condução de programas de controle de doenças e seleção de progenitores.

A blinded, randomized, placebo-controlled trial of the safety of oclacitinib in cats.

BACKGROUND: Oclacitinib is a Janus kinase (JAK) 1 enzyme inhibitor and blocks JAK1-dependent cytokines and is used to control pruritus. Studies available in cats are very limited and as there is a potential role for oclacitinib in the control of pruritus in this specie, the aim of this study was to evaluate the safety and clinical effects of oral oclacitinib maleate in healthy cats. RESULTS: Thirty mixed-breed cats weighing from 2.1 to 5.3 kg each were randomly allocated to three treatment groups of 10 animals each. Cats in two groups received oclacitinib at 1 mg/kg or 2 mg/kg q 12 h orally for 28 days. Cats in the third group were given placebo tablets (cornstarch) q 12 h orally for 28 days. Oclacitinib maleate was well tolerated during the study and few adverse events were observed in treated cats. Clinical signs of toxicity were not observed in any animals treated at 1 mg/kg. Gastrointestinal clinical signs observed in the 2 mg/kg group included vomiting in two of the 10 cats and soft stools in two cats. One cat treated with placebo also exhibited soft stools. No significant differences were observed between the groups for hematologic analyses performed during the study. There was a slight increase in neutrophils and monocytes and a decrease in eosinophil mean counts in treated cats. Mean renal and liver enzymes remained normal throughout the entire study. A small, but significant increase in fructosamine levels was observed for both treated groups compared with placebo; however, values remained within the normal reference range. There were no significant difference between treated groups and the placebo group for urine specific gravity, pH, or urine protein to creatinine ratio mean values. CONCLUSIONS: Oclacitinib maleate was well tolerated by cats at 1 mg/kg and 2 mg/kg and appeared to be safe for this species when administered orally twice daily for 28 days. More studies would be needed to demonstrate if oclacitinib maleate may be a suitable alternative to treat pruritic cats.

Evaluation of an inexpensive needle test for the diagnosis of phosphorus deficiency and management of phosphorus supplementation for cattle: A multiple case study.

The needle test (NT) is a point-of-care test developed in Brazil to evaluate the Phosphorus (P) status in cattle. Based on bone resistance, the NT is a very inexpensive method which allows the diagnosis of any degree of P deficiency in a fast and simple way in vivo and directly on farm. The NT measures three levels of resistance in the transverse process (TP) of the lumbar vertebrae: a) TP that are impenetrable and result in warping of the needle (P healthy animals); b) TP offering some resistance to the penetration (animals with subclinical P deficiency); and c) TP which has minimal resistance to penetration (clinical P deficiency). This manuscript presents results from a series of case studies to evaluate the hypothesis that the NT could be used to assess P status in cattle and assesses the usefulness of results to support decision making on mineral supplementation strategies for grazing cattle. The NT was able to detect the changes in the resistance patterns of the TP, as there was reduction or elevation of P levels in the mineral mixtures. The NT was useful to assist in decision-making for adoption of mineral supplementation strategies better suited for each farm, helping farmers to save money and avoid unnecessary waste of P.

Intestinal Lesion in a Dog Due to Cryptococcus gattii Type VGII and Review of Published Cases of Canine Gastrointestinal Cryptococcosis.

Cryptococcosis is a mycosis caused by yeasts of genus Cryptococcus, mainly the species C. neoformans and C. gattii that can affect humans and animals. These yeasts are widely distributed in the environment and are typically associated with avian droppings and decaying wood. Most infections are related to the respiratory tract, but the central nervous system and cutaneous lesions are also reported in the literature. The present report is a case of cryptococcosis in an 18-month-old unspayed female English Bulldog with the main complaint of weight loss and diarrhea. The presence of two large masses observed in an ultrasound examination leads us to perform an exploratory laparotomy. Considering the size of the lesion and the impossibility of owner to provide intensive care, the consent for euthanasia was requested. The postmortem diagnosis of cryptococcosis was revealed by cytological evaluation, and the involvement of C. gattii VGII was confirmed by isolation and identification tests as well as by the detection of the URA5 gene restriction fragment length polymorphism PCR analysis. Reports in the literature of the involvement of Cryptococcus in gastrointestinal lesions are rare in both human and veterinary medicine. Data about different forms of cryptococcosis are important to provide more knowledge of uncommon clinical presentations of this yeast and therefore improve the diagnoses and decisions for the best therapy.

Eficácia acaricida de uma emulsão contendo 10 por cento de óleo de nim (Azadirachta indica) no controle de Psoroptes ovis em coelhos naturalmente infestados / Miticidal efficacy of an emulsion containing 10 percent neem (Azadirachtaindica) oil for control of Psoroptes ovis in naturally infested rabbits

O objetivo do presente estudo foi avaliar a eficácia de uma emulsão contendo 10% de óleo de nim, Azadirachta indica, no controle de Psoroptes ovis em coelhos naturalmente infestados. Foram utilizados 12 coelhos separados aleatoriamente em dois grupos de seis animais cada. O grupo controle permaneceu sem tratamento, enquanto que o grupo tratado recebeu a formulação em teste, contendo 10% de Nim, borrifando ambos os condutos auditivos, uma vez ao dia, por sete dias consecutivos. Os animais foram avaliados diariamente para observação de possíveis efeitos adversos do produto. Nos dias +3, +7, +14,+21, +28 e +35 foi coletado material de todos os animais para avaliação da presença de ácaros vivos. Os coelhos do grupo controle apresentavam ácaros em ambos os condutos auditivos em todos os dias de observação. O grupo tratado apresentou eficácia de 41,7% no dia +3 e 100% a partir do dia +7 até o dia +35. O produto demonstrou ser eficaz no tratamento da sarna psoróptica em coelhos. Entretanto, todos os animais tratados apresentaram reações dermatológicas, tais como alopecia e hiperemia no local de aplicação do produto, variando de baixa a média severidade.

The objective of the present study was to evaluate the efficacy of an emulsion containing 10% of neem (Azadirachta indica) oil on the control of Psoroptes ovis in naturally infested rabbits. Twelve rabbits were randomly divided in two groups of six animals. The control group remained without treatment; while animals in the other group were treated with the 10% neem extract formulation by spraying both ears daily for seven consecutive days. The animals were evaluated daily for the presence of adverse effects. Material from ears all animals was collected on days +3, +7, +14, +21, +28 and +35, and evaluated for the presence of living mites. Animals from control group presented mites in both ears along all days of observation. The treated group presented an efficacy of 41.7% on day +3 and 100% from day +7 to +35. The product containing 10% neem oil has demonstrated to be effective for the treatment of psoroptic mange on rabbits. However, treated animals presented dermatological reaction such as alopecia and hyperemia at the site of application, varying from low to medium severity.

Avaliações clínico-patológicas e laboratoriais da intoxicação experimental por monofluoroacetato de sódio em ovinos / Clinic-pathological and laboratory aspects of experimental poisoning by sodium monofluoroacetate in sheep

O objetivo deste trabalho foi verificar se a administração de doses únicas e de frações diárias da dose letal de monofluoroacetato de sódio (MF) a ovinos induzem a clássica degeneração hidrópico-vacuolar (DHV) dos túbulos uriníferos contornados distais observada no rim de bovinos intoxicados por plantas brasileiras que causam "morte súbita" (PBCMS). MF foi administrado, por via oral, em doses únicas de 0,5 e 1,0mg/kg, cada dose para dois ovinos, e em doses subletais repetidas diariamente de 0,1mg/kg/dia, por quatro dias, e 0,2mg/kg/dia por seis dias, cada dose para um ovino. Todos os ovinos que receberam MF morreram, exceto um que recebeu 0,5mg/kg e não mostrou sintomas. A evolução da intoxicação variou de 3min a 33h5min. Clinicamente os animais apresentaram taquicardia, respiração abdominal, tremores musculares, ligeira perda de equilíbrio, por vezes cambaleavam, deitavam e apoiavam a cabeça no flanco. Na fase final, os ovinos caíam em decúbito lateral, esticavam os membros, faziam movimentos de pedalagem, apresentavam opistótono e morriam. O exame ecocardiográfico evidenciou dilatação cardíaca e redução da fração de encurtamento sistólico. A análise dos níveis séricos de uréia e creatinina revelou moderada a acentuada azotemia. MF provocou "morte súbita" em todos os ovinos que mostraram sintomas. À necropsia verificaram-se aurículas e veias jugulares, cavas, ázigos e pulmonares moderadamente ingurgitadas e, em alguns animais, edema pulmonar. O exame histopatológico revelou, em todos os ovinos, leve a acentuada DHV das células epiteliais dos túbulos contornados distais, associada à picnose nuclear. Adicionalmente, verificaram-se discreta vacuolização e, por vezes, necrose de coagulação de hepatócitos. Não encontramos referências a esse tipo peculiar de lesão, exceto das descrições sobre lesões renais associadas à ingestão de PBCMS e de recentes estudos em bovinos intoxicados com MF. Este trabalho demonstra, em ovinos, que tanto doses letais únicas quanto subdoses diárias de MF induzem a DHV dos túbulos uriníferos contornados distais associada à picnose nuclear.

The objective of this study was to verify if the ingestion of single doses of sodium monofluoroacetate (MF) and daily fractions of 1/2.5 and 1/5 of the lethal dose causes the same lesion as the one observed in the kidney of cattle poisoned by Brazilian sudden death causing plants (BSDCP). MF was administered orally in single doses of 0.5 and 1.0mg/kg to four sheep, and repeated daily doses of 0.1 and 0.2mg/kg to two others. Death occurred in five of six animals. The course of poisoning lasted from 3min to 33h5min. Clinically the animals presented palpitation, abdominal breathing, slight balance loss with sometimes swaying gait, they laid down and placed the head on their flank. In the "dramatic phase", all the sheep fell into lateral decubitus, stretched out the legs, made peddling movements, presented opistotonus, and died. The electrocardiographical examination showed heart dilatation and reduction of the systolic shortening fraction. Laboratory hematological exams revealed increased urea and creatinine. MF caused the clinical and pathological symptoms of "sudden death". At postmortem examination, heart auricles and jugular, cava, azygos and pulmonary veins of all animals were moderately engorged, and in some sheep, pulmonary edema was observed. Histopathology revealed hydropic-vacuolar degeneration (HVD) of the epithelial cells of the distal convoluted kidney tubules associated with nuclear picnosis in all the sheep. Vacuolation and less often necrosis of liver cells was seen in some cases. No references to that peculiar type of lesion could be found in the literature, except the description of kidney lesions in animals associated with the ingestion of BSDCP, and recent studies of MF poisoning in cattle. The present study demonstrated in sheep that single lethal doses or repeated doses of fractions of the lethal dose of MF causes HVD of the distal convoluted kidney tubules, associated with nuclear picnosis.