The quality of colostrum of Murciano-Granadina goats was studied to establish the 27 transition period and the time when milk can be marketed. Forty-three dairy goats were 28 used, 19 primiparous (15 single births; 4 multiple births) and 24 multiparous (10 single 29 births; 14 multiple births). Samples were collected every 12 h during the first week 30 postpartum. Physico-chemical parameters and somatic cell count were determined. 31Analysis of variance with repeated measures was used to study the effect of different 32 factors: postpartum time, litter size, lactation number, their interactions and production 33 level on colostrum. 34 Postpartum time had a significant effect on all parameters studied, which decreased 35 along the first week of lactation, while lactose, pH and conductivity increased. Based on 36 these results, colostrum secretion takes place until 36 hours postpartum (hpp). In 37 relation to other factors of variation studied, the lactation number influenced (P <0.05) 38 most colostrum components, while the litter size only affected (P <0.05) the pH value, 39 protein and lactose content. The production level influenced only the protein and dry 40 matter contents, with an inverse relationship. Milk produced during the period between 41 36 and 96 hpp is considered transition milk, which should not be commercialized. After 42 4 days postpartum (96 hpp) milk could be marketed, ensuring that composition does not 43 present a risk in the dairy industry. 44
The Charm maximum residue limit β-lactam and tetracycline test (Charm MRL BLTET; Charm Sciences Inc., Lawrence, MA) is an immunoreceptor assay utilizing Rapid One-Step Assay lateral flow technology that detects β-lactam or tetracycline drugs in raw commingled cow milk at or below European Union maximum residue levels (EU-MRL). The Charm MRL BLTET test procedure was recently modified (dilution in buffer and longer incubation) by the manufacturers to be used with raw ewe and goat milk. To assess the Charm MRL BLTET test for the detection of β-lactams and tetracyclines in milk of small ruminants, an evaluation study was performed at Instituto de Ciencia y Tecnologia Animal of Universitat Politècnica de València (Spain). The test specificity and detection capability (CCβ) were studied following Commission Decision 2002/657/EC. Specificity results obtained in this study were optimal for individual milk free of antimicrobials from ewes (99.2% for β-lactams and 100% for tetracyclines) and goats (97.9% for β-lactams and 100% for tetracyclines) along the entire lactation period regardless of whether the results were visually or instrumentally interpreted. Moreover, no positive results were obtained when a relatively high concentration of different substances belonging to antimicrobial families other than β-lactams and tetracyclines were present in ewe and goat milk. For both types of milk, the CCβ calculated was lower or equal to EU-MRL for amoxicillin (4 µg/kg), ampicillin (4 µg/kg), benzylpenicillin (≤ 2 µg/kg), dicloxacillin (30 µg/kg), oxacillin (30 µg/kg), cefacetrile (≤ 63 µg/kg), cefalonium (≤ 10 µg/kg), cefapirin (≤ 30 µg/kg), desacetylcefapirin (≤ 30 µg/kg), cefazolin (≤ 25 µg/kg), cefoperazone (≤ 25 µg/kg), cefquinome (20 µg/kg), ceftiofur (≤ 50 µg/kg), desfuroylceftiofur (≤ 50µg/kg), and cephalexin (≤ 50 µg/kg). However, this test could neither detect cloxacillin nor nafcillin at or below EU-MRL (CCβ >30 µg/kg). The CCβ for tetracyclines was also lower than EU-MRL for chlortetracycline (ewe milk: ≤ 50 µg/kg; goat milk: 75 µg/kg), oxytetracycline (≤ 50 µg/kg), and tetracycline (≤ 50 µg/kg). Regarding the 4-epimers of these tetracyclines only 4-epioxytetracycline was detected by the Charm MRL BLTET test below EU-MRL (ewe milk: 75 µg/kg; goat milk: ≤ 50 µg/kg). Acidiol had no effect on the performance of the test. The Charm MRL BLTET test could be used routinely with adapted test procedure for the fast screening of ewe and goat milk.
Phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are emerging as attractive therapeutic targets in diseases, such as cancer, immunological disorders, and neurodegeneration, owing to their central role in regulating cell signaling pathways that are either dysfunctional or can be modulated to promote cell survival. Different modes of binding may enhance inhibitor selectivity and reduce off-target effects in cells. Here, we describe efforts to improve the physicochemical properties of the selective PI5P4Kγ inhibitor, NIH-12848 ( 1 ). These improvements enabled the demonstration that this chemotype engages PI5P4Kγ in intact cells and that compounds from this series do not inhibit PI5P4Kα or PI5P4Kβ. Furthermore, the first X-ray structure of PI5P4Kγ bound to an inhibitor has been determined with this chemotype, confirming an allosteric binding mode. An exemplar from this chemical series adopted two distinct modes of inhibition, including through binding to a putative lipid interaction site which is 18 Å from the ATP pocket.
Albendazole (ABZ) residues in goat's milk and their effect on the response of microbial inhibitor tests used for screening antibiotics were evaluated. A total of 18 Murciano-Granadina goats were treated with ABZ and individually milked once a day over a 7-day period. ABZ quantification was performed by high performance liquid chromatography. The ABZ parent drug was not detected. The maximum concentration of its metabolites (ABZ sulfoxide, ABZ sulfone, and ABZ 2-aminosulfone) was reached on the 1 day post treatment (260.0 ± 70.1 μg/kg, 112.8 ± 28.7 μg/kg, 152.0 ± 23.6 μg/kg, respectively), decreasing to lower than the maximum residue limit (MRL, 100 μg/kg) on the 3 day post treatment. Milk samples were also analyzed by microbial tests [Brilliant Black Reduction Test (BRT) MRL, Delvotest SP-NT MCS and Eclipse 100], and only one positive result was found for Delvotest SP-NT MCS and Eclipse 100. However, a high occurrence of positive outcomes was obtained for BRT MRL during 6 days post treatment, whereas ABZ residues were not detected from the 4 day post administration, suggesting that factors other than the antiparasitic agent might affect the microbial test response.
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