Are γ-terpinene, 1,8-cineole, p-coumaric acid, and quercetin active against wild-type and non-wild-type Sporothrix brasiliensis to itraconazole?

The emergence of itraconazole (ITZ)-resistant Sporothrix brasiliensis in feline and canine cases in southern Brazil has hampered the clinical cure of animal sporotrichosis, encouraging the search for therapeutic alternatives. The promising use of plants extracts from Lamiaceae family is known; however, there are no studies with its major compounds, as γ-terpinene (γTER), 1,8-cineole (1,8CIN), p-coumaric acid (pCOU), and quercetin (QUER). For the first time, we evaluated the antifungal, synergistic, cytotoxic activities and action mechanism of these compounds against S. brasiliensis. For this, 28 S. brasiliensis from cats (n = 24) and dogs (n = 4) and standard strains of S. brasiliensis and S. schenckii (n = 4) were tested by M38-A2 (CLSI), revealing non-wild-type (WT) isolates to ITZ on 54.2% (13/24) and 75% (03/04) of feline and canine isolates, respectively. Of the compounds, γTER stood out against all isolates (MIC/MFC 0.75 to > 3 mg/ml; MIC50 3 mg/ml). However, 1,8CIN, pCOU, and QUER showed little or no activity (MIC50 > 3 mg/ml). Thus, γTER was selected for checkerboard assay, whose combination with ITZ showed synergistic (WT isolates) and indifferent (non-WT isolates) interaction. For action mechanism (sorbitol protection and ergosterol effect), γTER acted in membrane by complexing with fungal ergosterol and at the cell wall level, showing two possible pathways as antifungal target. Finally, cytotoxicity (MTT assay) showed that γTER was the safest compound on MDBK cells, even at a concentration of 3 mg/ml (90.16%). Our findings support that γTER is a potent antifungal candidate for the control of sporotrichosis, including against non-WT S. brasiliensis.

Meroanencephaly in an English Pointer neonate

Background: Malformations are structural or functional abnormalities in the organs and structures present at birth. Theseconditions are rarely described in the newborns of dogs and can lead to their death. Meroanencephaly is a defect of theneural tube closure malformation, a type of anencephaly and results from a failure of closure of the rostral neuropore(neural crest), and consequently the development of the calvary becomes defective. This study aims to characterize theclinical-pathological aspects of neonatal meroanencephaly since brain malformations are rare in newborn dogs.Case: A 2-day-old English Pointer canine was sent for a necropsy. The newborn belonged to a litter of eight puppies, andonly this one had macroscopic cranial alterations. Another puppy that died as a consequence of being trampled by thebitch was also necropsied. The newborn was alive for 48 h until death and presented apathy, crying, sucking reflex andopisthotonus. Macroscopic examination of the baby revealed flattening of the skull, with a slit at the site of bone symphysis fusion, and a slit in the skin of the parietal region, covered by thin, translucent meningeal tissue. The newborn hadno other macroscopic changes. The heads of the two animals were examined by radiography to identify the features ofanencephaly in one of the animals by visualizing skull bone flattening. Upon removing the skin and exposing the cranialcavity, an irregular reddish mass was revealed, that corresponded microscopically to area cerebrovasculosa, composed ofneurons and rudimentary glial tissue, vascular neoformation and, hemorrhage and congestion. The cranial nerves was notpossible to observe. There was disorganization of the brain areas with no limitation of white and gray matter and scarceneurons and also a region similar to the cerebellum, with a molecular layer but without the Purkinje neurons. In the spinal...(AU)

Meroanencephaly in an English Pointer neonate

Background: Malformations are structural or functional abnormalities in the organs and structures present at birth. Theseconditions are rarely described in the newborns of dogs and can lead to their death. Meroanencephaly is a defect of theneural tube closure malformation, a type of anencephaly and results from a failure of closure of the rostral neuropore(neural crest), and consequently the development of the calvary becomes defective. This study aims to characterize theclinical-pathological aspects of neonatal meroanencephaly since brain malformations are rare in newborn dogs.Case: A 2-day-old English Pointer canine was sent for a necropsy. The newborn belonged to a litter of eight puppies, andonly this one had macroscopic cranial alterations. Another puppy that died as a consequence of being trampled by thebitch was also necropsied. The newborn was alive for 48 h until death and presented apathy, crying, sucking reflex andopisthotonus. Macroscopic examination of the baby revealed flattening of the skull, with a slit at the site of bone symphysis fusion, and a slit in the skin of the parietal region, covered by thin, translucent meningeal tissue. The newborn hadno other macroscopic changes. The heads of the two animals were examined by radiography to identify the features ofanencephaly in one of the animals by visualizing skull bone flattening. Upon removing the skin and exposing the cranialcavity, an irregular reddish mass was revealed, that corresponded microscopically to area cerebrovasculosa, composed ofneurons and rudimentary glial tissue, vascular neoformation and, hemorrhage and congestion. The cranial nerves was notpossible to observe. There was disorganization of the brain areas with no limitation of white and gray matter and scarceneurons and also a region similar to the cerebellum, with a molecular layer but without the Purkinje neurons. In the spinal...