Treatment Of Mastitis Research Articles

Shear Wave Elastography-Correlated Dose Modifying: Can We Reduce Corticosteroid Doses in Idiopathic Granulomatous Mastitis Treatment? Preliminary Results

Idiopathic granulomatous mastitis (IGM) is a chronic inflammatory breast disease treated with local and systemic corticosteroids. This study aims to evaluate the efficacy of reducing corticosteroids doses in IGM cases based on shear wave elastography (SWE) tissue stiffness measurements. This prospective study included IGM patients who received systemic or local corticosteroids between January 2020 and September 2022. A 20% or more reduction in tissue elasticity values (kPa) was considered a positive response to treatment in the study group, and the corticosteroids dose was reduced. The control group was dosed routinely. All patients were followed for 2 years to compare treatment efficacy, duration, total corticosteroids dose, recurrence, and side effects. There were 12 patients (9 local/3 systemic corticosteroids) in the study group and 24 patients (17 local/7 systemic corticosteroids) in the control group. Ten (83.4%) out of 12 patients in the study group were successfully treated by reducing corticosteroid doses with follow-up, and 2 (16.6%) out of 12 patients were reverted to the initial treatment protocol due to an increase in elasticity values during the follow-up. Nevertheless, successful treatment results were obtained in these two patients without reducing the corticosteroid dose. When compared to the control group, the median corticosteroid dose in the study group was significantly lower in patients using both local (p < 0.01) and systemic (p < 0.01) corticosteroids. A significant negative correlation was found between the rate of decrease in elasticity values and the median dose of corticosteroids (r = -0.649, p < 0.05) and the median treatment time (r = -0.751, p < 0.01). Side effects due to corticosteroids were found to be significantly lower in the study group (p < 0.05). According to our first and preliminary results, the SWE-correlated dose-modifying technique may reduce corticosteroid doses and side effects without significantly compromising treatment efficacy.

Evaluation of acoustic pulse technology as a non-antibiotic therapy for bovine intramammary infections: Assessing bacterial cure vs. recovery from inflammation.

The spread of antimicrobial resistance (AMR) is a major threat to human and animal health. Therefore, new solutions are needed to prevent returning to a world without effective antibiotics. Mastitis in dairy cows is a major reason for antimicrobial use in food animal production, and mastitis-causing bacteria have the potential to develop AMR. In this study, acoustic pulse technology (APT) was explored as an alternative to antimicrobials for the treatment of mastitis in dairy cows. APT involves the local transmission of mechanical energy through soundwaves which stimulate anti-inflammatory and angiogenic responses in the udder. These responses promote udder recovery and enhance resistance to bacterial infections. We examined 129 Israeli dairy cows with mastitis in this prospective, controlled study to assess the efficiency of APT treatment on cure and recovery rates. An accurate diagnosis of suspected or confirmed infectious mastitis was made from cows having clinical signs of mastitis and/or somatic cell count (SCC) of above 400,000 cells/mL. The cows were divided into three groups: Group 1 (n = 29), cows with no bacterial findings (NBF); Group 2 (n = 82), cows with clinical signs of mastitis or SCC >400,000 cells/mL in the most recent test; and Group 3 (n = 18), cows with chronic mastitis (two or more tests with SCC >400,000 cells/mL within 3 months). All the cows received APT treatment, which involved 400 pulses on two sides of the infected quarter, delivered in three phases over 3 days. The cure for the mammary gland was indicated by the absence of bacterial growth in post-treatment cultures and recovery by a decrease in SCC to < 250,000 cells/mL in two of three post-treatment tests. In Group 2, cure and recovery rates were 67.1 and 64.6%, respectively, and were not significantly different between Gram-negative and Gram-positive infections. A similar recovery rate was found in NBF cows. However, in cows with chronic mastitis, both the cure and recovery rates were significantly lower (22.2 and 27.8%, respectively). These results have important implications for dairy farmers, as APT treatment could lead to substantial savings of up to $15,106/year in a 100-cow herd, considering the national estimated prevalence of mastitis and the cost of individual treatment. APT should be further investigated as a viable and sustainable alternative to antimicrobial therapy for mastitis, offering economic benefits to dairy producers and the possibility of preventing AMR.

Comparative efficacy of local and parenternal therapies in treatment of clinical mastitis in buffaloes

Comparative efficacy of local and parenternal therapies in treatment of clinical mastitis in buffaloes

Anti-Inflammatory Activity of Glyceryl 1,3-Distearate Identified from Clinacanthus nutans Extract against Bovine Mastitis Pathogens

Clinacanthus nutans is widely used as a traditional medicine in Thailand and other countries in Southeast Asia. Although its effectiveness is well documented, its therapeutic use is limited to the treatment of only a few diseases; mostly it is used as an anti-viral agent against varicella-zoster and herpes simplex virus infections. Herein, we demonstrate the therapeutic activity of C. nutans extracts in lowering inflammation in a model of bovine mastitis caused by bacterial infection. Lipopolysaccharide (LPS), a gram-negative bacterial component, caused inflammation activation in bovine endothelial cells (CPAE) through the upregulation of proinflammatory cytokines (IL6 and IL1β) and chemokines (CXCL3 and CXCL8) gene expression, partially leading to cell death. Treatment with C. nutans crude extract significantly diminished these responses in a dose-dependent manner. The solvent fractionation of C. nutans extract revealed that the ethyl acetate (C4H8O2) fractions had a high potential to protect against cell death and diminished IL1β, IL6, CXCL3, and CXCL8 levels to less than 0.45 folds relative to the LPS-treated control. Glyceryl 1,3-distearate (C39H76O5) was identified as a bioactive compound responsible for the anti-inflammation activity but not the anti-cell death activity of C. nutans extract. This study highlighted the efficiency of C. nutans extracts as an alternative therapeutic option for the natural-product sustainable development of bovine mastitis treatment.

MULTIDRUG-RESISTANT STAPHYLOCOCCUS AUREUS ISOLATED FROM CATTLE MILK IN INDONESIA

Staphylococcus aureus (S. aureus) is one of the common causes of bovine mastitis worldwide. Inappropriate use of antimicrobials in cattle farms contributes to the increase of the antimicrobial resistance of S. aureus. This study aimed to investigate the antimicrobial resistance profiles of S. aureus isolated from cattle milk. Twelve S. aureus isolated from cattle milk in Bogor, Indonesia, were tested against seven antimicrobials using Kirby-Bauer disk diffusion susceptibility test. The results revealed that 58.3 % of isolates were multidrug-resistant S. aureus. The S. aureus isolates were resistant to penicillin G (66.7 %), ampicillin (66.7 %), vancomycin (58.3 %), and bacitracin (58.3 %). Most of the isolates were susceptible to ciprofloxacin (91.7 %), gentamicin (66.7 %), and chloramphenicol (66.67 %). If clinically indicated, treatment of mastitis should consider the antimicrobial susceptibility of the causative agent.

Exogenous Melatonin Enhances the Yield and Secondary Metabolite Contents of Prunella vulgaris by Modulating Antioxidant System, Root Architecture and Photosynthetic Capacity

Melatonin (MT) plays a number of key roles in regulating plant growth and secondary metabolite accumulation. Prunella vulgaris is an important traditional Chinese herbal medicinal plant which is used for the treatment of lymph, goiter, and mastitis. However, the effect of MT on the yield and medicinal component content of P. vulgaris remains still unclear. In this research, we have examined the influence of different concentrations of MT (0, 50, 100, 200, 400 μM) on the physiological characteristics, secondary metabolite contents, and yield of P. vulgaris biomass. The results showed that 50-200 μM MT treatment had a positive effect on P. vulgaris. MT treatment at 100 μM greatly increased the activities of superoxide dismutase and peroxidase, the contents of soluble sugar and proline, and obviously decreased the relative electrical conductivity, the contents of malondialdehyde and hydrogen peroxide of leaves. Furthermore, it markedly promoted the growth and development of the root system, increased the content of photosynthetic pigments, improved the performance of photosystems I and II and the coordination of both photosystems, and enhanced the photosynthetic capacity of P. vulgaris. In addition, it significantly increased the dry mass of whole plant and spica and promoted the accumulation of total flavonoids, total phenolics, caffeic acid, ferulic acid, rosmarinic acid, and hyperoside in the spica of P. vulgaris. These findings demonstrated that the application of MT could effectively activate the antioxidant defense system of P. vulgaris, protect the photosynthetic apparatus from photooxidation damage, and improve the photosynthetic capacity and the root absorption capacity, thereby promoting the yield and accumulation of secondary metabolites in P. vulgaris.

Comparative study of ultrasound-guided microwave ablation and traditional surgery in the treatment of plasma cell mastitis: a multicenter study.

Plasma cell mastitis (PCM) is a benign breast disease that is refractory and difficult to cure. We integrated microwave ablation into the treatment of PCM to compare the clinical value of ultrasound-guided microwave ablation and traditional surgery in the treatment of PCM. A total of 68 patients with PCM who were admitted to 3 centers (Zhejiang Cancer Hospital, Hebei Province Hospital of Traditional Chinese Medicine, and Yantai Affiliated Hospital of Binzhou Medical university) from January 2017 to June 2019 were selected. All patients were diagnosed with PCM after pathological and clinical manifestations. Among these, 38 cases were treated with ultrasound-guided microwave ablation, and 30 cases were treated with traditional surgery. The operation time, hospitalization time, incision healing, intraoperative blood loss, postoperative pain degree, evaluation of breast shape effect, time taken for postoperative lesion disappearance, effective rate, and recurrence were recorded in the follow-up, and the clinical efficacy was compared and observed. The effective rate of the ablation group was 86.8% (33/38), that of the operation group was 46.7% (14/30), and the difference was statistically significant (95% CI: 2.311-24.618; P<0.05). The average time of the lesion completely disappearing was 75.55±43.59 days in the ablation group and 103.87±45.98 days in the operation group, and the difference was statistically significant (P<0.05). The hospital stays, operation time, and intraoperative blood loss of patients in the ablation group were less than those of the operation group, and the difference was statistically significant (95% CI: -10.69 to -6.27, 95% CI: -77.06 to -51.26, and 95% CI: -21.54 to -13.64; P<0.05). The postoperative pain scoring, operative incision healing at 14 days after the operation, and breast appearance evaluation after treatment in the ablation group were better than those of the operation group, and the difference was statistically significant (P<0.05). Compared with traditional surgery, ultrasound-guided microwave ablation is a more effective treatment option for PCM.

PREVALENCE, ANTIMICROBIAL RESISTANCE PROFILES OF CLINICAL AND SUBCLINICAL MASTITIS IN LACTATING COW WITH ASSESSMENT OF TREATMENT TRIAL

This work investigated the prevalence of bovine mastitis in a dairy farm, Ismalia governrate, Egypt with phynotypic and genotypic clarification of the causative bacteria and their antimicrobial susceptibility. Also a treatment trial with a combination of Cafalexin, Kanamycin was evaluated. The total prevalence of mastitis was 31.82% (119/374) at cow level and 17.01% (247/1452) at quarter level. 261 isolates were detected. (74.33%) belong to staphylococcus spp and (25.67%) to streptococcus spp. as major microorganisms (CNS (42.53%) s.aurus (31.80%) s. uberis (12.26%), s. agalactia (8.81%) and s. dysagalactia(4.59%). The isolates were tested against 15 antimicrobial agents and the highest percentage of resistant bacteria was for AMC, P, C and E. while the lowest rate was for CN, CIP, CL and K. Molecular Characterization of isolated pathogens and antimicrobial resistance genes was performed by PCR on 15 isolates. blaTEM-1 Was the most frequently detected gen followed by aadA1, dfrA1, cmlA, sul1, and tetA. 110 infected udder quarters were enrolled for 21 days to evaluate the treatment with Terrexine LC intramammary suspension 10g on six occasions at 12 h intervals and gentamycin intramuscular injection (1cm/20kg Bw for 3-5 days in cows with systemic reaction. A high significant reduction was recorded for the log10 SSC, log10 TBC and the level of LDH in milk after treatment compared their level before treatment (P-value &lt;0.0001***). The milk season for cows, degree of mastitis or type of microorganism isolated before treatment have no effect on the recovery rate P-value ˃0.05. In conclusion, the emergence of multidrug-resistant strains is greatly increased so antibiotic usage must be Restricted. PCR can help in the rapid detection of the resistant strains. Treatment of mastitis with combination of antimicrobial may reduce drug resistance. Bovine mastitis still needs updated knowledge on the causative microbes and their antibiotic resistance patterns for optimal control and treatment.

Recent Trends of Antibiotic Resistance in Staphylococcus aureus Causing Clinical Mastitis in Dairy Herds in Abruzzo and Molise Regions, Italy.

This study aimed to investigate the recent trends of antibiotic resistance (AR) prevalence in Staphylococcus aureus isolated from the milk of animals with clinical mastitis in areas of the Abruzzo and Molise regions in Central Italy. Fifty-four S. aureus isolates were obtained from routine testing for clinical mastitis agents carried out in the author institution in the years 2021 and 2022 and were analyzed for phenotypic resistance to eight antibiotics recommended for testing by European norms and belonging to the antibiotic classes used for mastitis treatment in milk-producing animals. Moreover, the presence of 14 transferable genetic determinants encoding resistance to the same antibiotics was analyzed using qPCR tests developed in this study. Phenotypic resistance to non-β-lactams was infrequent, with only one 2022 isolate resistant to clindamycin. However, resistance to the β-lactam cefoxitin at concentrations just above the threshold of 4 µg/mL was observed in 59.2% of isolates in both years, making these isolates classifiable as methicillin-resistant. The AR genotypes detected were the blaZ gene (50% of 2021 isolates and 44.4% of 2022 isolates), aphA3-blaZ- ermC/T (one 2021 isolate), aphA3-ant6-blaZ-ermC/T (one 2021 isolate), blaZ-ermB (one 2022 isolate) and mecA-mph (one 2022 isolate). An inquiry into the veterinarians who provided the samples, regarding the antimicrobials prescribed for mastitis treatment and criteria of usage, indicated a possible causal relation with the AR test results. The occurrence of AR genotypes did not increase in time, most probably reflecting how mastitis was treated and prevented in farms. However, the frequently observed cefoxitin resistance needs to be explained genotypically, further monitored and limited by modifying antibiotic usage practices. The identification of a mecA-positive isolate in 2022 suggests further investigation if this genotype is emerging locally.

Effects of Intramammary Antimicrobial Treatment on the Milk Microbiota Composition in Mild Clinical Bovine Mastitis Caused by Gram-Positive Bacteria

The purpose of this study was to clarify the effects of antimicrobial treatment for mild mastitis caused by Gram-positive bacteria on the milk microbiota in dairy cattle. Sixteen quarters of sixteen cows with mild clinical mastitis from the same herd were included in the study. On the day of onset (day 0), the cows were randomly allocated to a no-treatment (NT; n = 10) group or an intramammary antimicrobial treatment (AMT) group that received AMT starting on day 0 (AMT-AMT group; n = 6). The next day (day 1), the cows in the NT group were randomly allocated into an NT group (NT-NT group; n = 3) that received no treatment or an AMT group that received AMT starting on day 1 (NT-AMT group; n = 7). Milk samples were collected on days 0, 1, 3 and 7, and the milk microbiota of each sample was comprehensively analyzed via 16S rRNA gene amplicon sequencing of the milk DNA. During the treatment period, the milk microbiota of the NT-NT group did not change, but those of the NT-AMT and AMT-AMT groups changed significantly on days three and seven. Thus, the use of antimicrobials for mild mastitis caused by Gram-positive bacteria changes the milk microbiota composition.

Geraniol-a potential alternative to antibiotics for bovine mastitis treatment without disturbing the host microbial community or causing drug residues and resistance.

Mastitis is one of the most prevalent diseases of dairy cows. Currently, mastitis treatment in dairy cows is mainly based on antibiotics. However, the use of antibiotics causes adverse effects, including drug resistance, drug residues, host-microbiome destruction, and environmental pollution. The present study sought to investigate the potentiality of geraniol as an alternative to antibiotics for bovine mastitis treatment in dairy cows. Additionally, the effectiveness of treatment, improvement in inflammatory factors, the influence on microbiome, presence of drug residues, and drug resistance induction were compared and analyzed comprehensively.Geraniol showed an equivalent therapeutic rate as antibiotics in the mouse infection model and cows with mastitis. Moreover, geraniol significantly inhibited the pathogenic bacteria and restored the microbial community while increasing the abundance of probiotics in milk. Notably, geraniol did not destroy the gut microbial communities in cows and mice, whereas antibiotics significantly reduced the diversity and destroyed the gut microbial community structure. Additionally, no geraniol residue was detected in milk four days after treatment discontinuation, but, antibiotic residues were detected in milk at the 7th day after drug withdrawal. In vitro experiments revealed that geraniol did not induce drug resistance in the Escherichia coli strain ATCC25922 and Staphylococcus aureus strain ATCC25923 after 150 generations of culturing, while antibiotics induced resistance after 10 generations. These results suggest that geraniol has antibacterial and anti-inflammatory effects similar to antibiotics without affecting the host-microbial community structure or causing drug residues and resistance. Therefore, geraniol can be a potential substitute for antibiotics to treat mastitis or other infectious diseases and be widely used in the dairy industry.

Allicin Alleviated LPS-Induced Mastitis via the TLR4/NF-κB Signaling Pathway in Bovine Mammary Epithelial Cells.

Dairy farming is the most important economic activity in animal husbandry. Mastitis is the most common disease in dairy cattle and has a significant impact on milk quality and yield. The natural extract allicin, which is the main active ingredient of the sulfur-containing organic compounds in garlic, has anti-inflammatory, anticancer, antioxidant, and antibacterial properties; however, the specific mechanism underlying its effect on mastitis in dairy cows needs to be determined. Therefore, in this study, whether allicin can reduce lipopolysaccharide (LPS)-induced inflammation in the mammary epithelium of dairy cows was investigated. A cellular model of mammary inflammation was established by pretreating bovine mammary epithelial cells (MAC-T) with 10 µg/mL LPS, and the cultures were then treated with varying concentrations of allicin (0, 1, 2.5, 5, and 7.5 µM) added to the culture medium. MAC-T cells were examined using RT-qPCR and Western blotting to determine the effect of allicin. Subsequently, the level of phosphorylated nuclear factor kappa-B (NF-κB) was measured to further explore the mechanism underlying the effect of allicin on bovine mammary epithelial cell inflammation. Treatment with 2.5 µM allicin considerably decreased the LPS-induced increase in the levels of the inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) and inhibited activation of the NOD-like receptor protein 3 (NLRP3) inflammasome in cow mammary epithelial cells. Further research revealed that allicin also inhibited the phosphorylation of inhibitors of nuclear factor kappa-B-α (IκB-α) and NF-κB p65. In mice, LPS-induced mastitis was also ameliorated by allicin. Therefore, we hypothesize that allicin alleviated LPS-induced inflammation in the mammary epithelial cells of cows probably by affecting the TLR4/NF-κB signaling pathway. Allicin will likely become an alternative to antibiotics for the treatment of mastitis in cows.

Adjuvant activity of tubeimosides by mediating the local immune microenvironment.

Rhizoma Bolbostemmatis, the dry tuber of Bolbostemma paniculatum, has being used for the treatment of acute mastitis and tumors in traditional Chinese medicine. In this study, tubeimoside (TBM) I, II, and III from this drug were investigated for the adjuvant activities, structure-activity relationships (SAR), and mechanisms of action. Three TBMs significantly boosted the antigen-specific humoral and cellular immune responses and elicited both Th1/Th2 and Tc1/Tc2 responses towards ovalbumin (OVA) in mice. TBM I also remarkably facilitated mRNA and protein expression of various chemokines and cytokines in the local muscle tissues. Flow cytometry revealed that TBM I promoted the recruitment and antigen uptake of immune cells in the injected muscles, and augmented the migration and antigen transport of immune cells to the draining lymph nodes. Gene expression microarray analysis manifested that TBM I modulated immune, chemotaxis, and inflammation-related genes. The integrated analysis of network pharmacology, transcriptomics, and molecular docking predicted that TBM I exerted adjuvant activity by interaction with SYK and LYN. Further investigation verified that SYK-STAT3 signaling axis was involved in the TBM I-induced inflammatory response in the C2C12 cells. Our results for the first time demonstrated that TBMs might be promising vaccine adjuvant candidates and exert the adjuvant activity through mediating the local immune microenvironment. SAR information contributes to developing the semisynthetic saponin derivatives with adjuvant activities.

Intramammary Ethno-Veterinary Formulation in Bovine Mastitis Treatment for Optimization of Antibiotic Use.

Increasing pressure on animal and human health as well as food security, due to antimicrobial resistance, is leading to increased demand for natural-product-derived antibiotics worldwide. Considering the importance of bovine mastitis as well as the huge challenge posed by mastitis therapy in cattle production, the main goal of this research was to evaluate the effectiveness of the essential oil-based pharmaceutical (Phyto-Bomat), as an alternative to the existing treatment with antibiotics. The therapeutic response of the cows was monitored using clinical and bacteriological cure of the proposed formulation. Among 550 dairy cows, 75 were diagnosed with a clinical or subclinical form of mastitis and divided into three experimental groups: treated with antibiotic; Phyto-Bomat; antibiotic and Phyto-Bomat. Indicators of bacteriological cure were somatic cell count (SCC), total bacterial count, and causative agent isolation, while the clinical cure was accessed by observing physical udder conditions. All mentioned indicators were assessed before and after the treatment (1st and 7th day post-treatment), with all of the three therapeutic protocols. After Phyto-Bomat treatment, no visible signs of irritation were noticed, while no significant effect in reducing SCC and total bacterial count was observed. Phyto-Bomat has shown promising results in the treatment of mastitis, without the risk of udder irritation, alone or in combination with antibiotics as part of a mastitis control program during lactation.

Indicators of mammary gland secretion in cows with subclinical mastitis when using interferon-λ

The largest number of currently produced drugs for the treatment of mastitis in lactating cows contain antimicrobial components (antibiotics) as active substances. The studies were carried out on Red-Motley Holstein cows, in which subclinical mastitis was diagnosed. The animals selected for the experiment were divided into three groups. The first group included 8 animals, they were not treated and served as a negative control. In the second group, 10 cows were selected for treatment with Biferon-B for three days once a day at a dose of 10 ml. per animal. The animals of the third group were simultaneously administered interferon-λ and BiferonB intramuscularly, 10 ml each during those days. According to the results of clinical studies, it was found that no recovery was recorded in the animals in the negative control group. In the group of animals where Biferon-B was used, the efficacy of treatment was 60.0%, and with the combined use of Biferon-B and interferon-λ, the effect of treatment was 83.3%. In these animals, the number of somatic cells decreased by 14.3 times, the concentration of neutrophils – by 2.6 times, the amount of total Ig - by 67.5%, CIC - by 61.5%, against the background of an increase in the number of lymphocytes by 6.0 times, monocytes - by 2.1 times and lysozyme - by 45.3%, and the bacterial contamination of the udder secretion also decreased to 0.08 thousand CFU/ml, which was by 120 times less compared to the initial state. Only Escherichia coli has been isolated from the udder secretion in 20.0% of cases that confirms the clinical efficacy of the treatment.

Effect of matrine in MAC-T cells and their transcriptome analysis: A basic study.

Matrine, an alkaloid derived from herbal medicine, has a wide range of biological activities, including antibacterial. Matrine was toxic to multiple cells at high concentrations. Bovine mammary epithelial cells (MAC-T) could be used as model cells for cow breast. Matrine was a feasible option to replace antibiotics in the prevention or treatment of mastitis against the background of prohibiting antibiotics, but the safe concentration of matrine on MAC-T cells and the mechanism of action for matrine at different concentrations were still unclear. In this study, different concentrations of matrine (0.5, 1, 1.5, 2, 2.5 and 3 mg/mL) were used to treat MAC-T cells for various time periods (4, 8, 12, 16 and 24 h) and measure their lactic dehydrogenase (LDH). And then the optimal doses (2 mg/mL) were chosen to detect the apoptosis at various time periods by flow cytometry and transcriptome analysis was performed between the control and 2 mg/mL matrine-treated MAC-T cells for 8 hours. The results showed that matrine was not cytotoxic at 0.5 mg/mL, but it was cytotoxic at 1~3 mg/mL. In addition, matrine induced apoptosis in MAC-T cells at 2 mg/mL and the proportion of apoptosis cells increases with time by flow cytometry. RNA-seq analysis identified 1645 DEGs, 676 of which were expressed up-regulated and 969 were expressed down-regulated. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated the following pathways were linked to matrine-induced toxicity and apoptosis, including cytokine-cytokine receptor interaction pathway, viral protein interaction with cytokine and cytokine receptor, P53 and PPAR pathway. We found 7 DEGs associated with matrine toxicity and apoptosis. This study would provide a basis for the safety of matrine in the prevention or treatment of mastitis.

The pharmacokinetics and pharmacodynamics of cefquinome against Streptococcus agalactiae in a murine mastitis model.

Cefquinome is a new generation cephalosporin that is effective in the treatment of mastitis in animals. In this study, we evaluated the associations between the specific pharmacokinetics and pharmacodynamics (PK/PD) of cefquinome and its antibacterial activity against Streptococcus agalactiae in a mouse model of mastitis. After a single intramammary dose of cefquinome (30, 60, 120, and 240 μg/mammary gland), the concentration of cefquinome in plasma was analysed by liquid chromatography with tandem mass spectrometry (HPLC/MS-MS). The PK parameters were calculated using a one-compartment first-order absorption model. Antibacterial activity was defined as the maximum change in the S. agalactiae population after each dose. An inhibitory sigmoid Emax model was used to evaluate the relationships between the PK/PD index values and antibacterial effects. The duration for which the concentration of the antibiotic (%T) remained above the minimum inhibitory concentration (MIC) was defined as the optimal PK/PD index for assessing antibacterial activity. The values of %T > MIC to reach 0.5-log10CFU/MG, 1-log10 CFU/MG and 2-log10 CFU/MG reductions were 31, 47, and 81%, respectively. When the PK/PD index %T > MIC of cefquinome was >81% in vivo, the density of the Streptococcus agalactiae was reduced by 2-log10. These findings provide a valuable understanding to optimise the dose regimens of cefquinome in the treatment of S. agalactiae infections.

Management-Associated Risk Factors for Heifer Mastitis before and after Parturition in German Dairy Herds.

Subclinical mastitis in heifers during early lactation affects udder health, future milk production and, therefore, the risk of premature culling. The aim of this cross-sectional study was to identify pre- and post-partum risk factors associated with a high heifer mastitis rate (HMR), and to find out which period (either pre- or post-partum) contains more risk factors and consequently should be the focus of mastitis control in heifers. A total of 77 herds were included in this study and the potential animal- and farm-related risk factors were recorded during a one-time farm visit. The HMR was provided by the dairy herd improvement test (DHI) as the annual average of the past 11 DHIs. For this study, data were analyzed in two models using generalized linear models. Each model examined the association between possible risk factors and HMR, one including only prepartum risk factors and the other one only post-partum risk factors. One identified pre-partum risk factor was the proportion of udder-healthy cows in the herd. Post-partum risk factors were the type of teat cleaning procedure before milking, teat disinfection, treatment of mastitis in heifers, a body condition score (BCS) of >3.0 in fresh heifers, and the combination of a teat cleaning procedure with a teat disinfectant. The results show the importance of the period shortly after calving for udder health in heifers, as four of the five significant risk factors were identified in this period and three of them were related to the milking process. However, further research with a higher number of herds is needed to minimize individual herd effects.

A PK/PD model for the evaluation of clinical rifaximin dosage for the treatment of dairy cow mastitis induced by Escherichia coli

Escherichia coli (E. coli) is an opportunistic pathogen that can cause clinical mastitis in dairy cows worldwide. Mastitis produces severe symptoms in dairy cows, such as udder inflammation, the production of harmful substances, reduced milk production, and altered milk quality. Intramammary injections of rifaximin have a beneficial effect on dairy cow mastitis, especially for mastitis caused by E. coli. However, we do not know whether the currently accepted clinical administration scheme is reasonable. Therefore, the purpose of this experiment was to evaluate the clinical dosing regimen for curing mastitis induced by E. coli. In this study, the pharmacokinetics of four single dose groups (50, 100, 200, and 400 µg/gland) were studied in CD-1 lactating mice, and the main pharmacokinetic parameters were obtained by non-compartment and two-compartment model of Phoenix 8.1 software. A total of 5,000 colony-forming units (CFU) of E. coli ATCC25922 were injected into the mammary glands of mice under anatomic microscope guidance. After 12 h of growth in vivo, the mouse mastitis model was successfully developed. In pharmacodynamics experiment, 12 different dosing regimens (doses ranged from 25 to 800 µg/gland and two dosing intervals of 12 and 24 h) were used to study the therapeutic potential of rifaximin for mastitis. The PK/PD model was established by integrating pharmacokinetics and pharmacodynamics using the inhibitory sigmoid Emax model. The optimal antibacterial effect was 2log10CFU/gland reduction of bacterial colony counts in vivo, when the magnitude of AUC24/MIC exceeded 57.80 h. A total of 57.80 h of AUC24/MIC was defined as a target value in the Monte Carlo simulation. The clinically recommended dosage regimen of 100 mg/gland every 12 h in a day achieved a 91.08% cure rate for the treatment of bovine mastitis caused by E. coli infection.

Copaiba Oil-Based Emulsion as a Natural Chemotherapeutic Agent for the Treatment of Bovine Mastitis: In Vivo Studies

Copaiba oil-resin (COR) extracted from Copaifera reticulata Ducke has been used as a natural chemotherapeutic agent for a wide range of therapeutic applications. This study presents an emulgel design with a high concentration of COR, designed to prevent and treat mastitis. The COR was stabilized in a gel matrix constituted by carbopol C934P and Pluronic® F127 (ECO formulation) ratios. The permeation study of ECO was accessed by Fourier transform infrared photoacoustic spectroscopy (FTIR-PAS). The results reveal a high capacity of ECO to permeate deep skin layers. Dairy cows with a history of mastitis were used as in vivo models and exposed to ECO treatment. Monitoring of the teat's inflammatory response showed that ECO effectively prevents mastitis. Furthermore, the ECO formulation was able to form a thin film gel on the application side, preventing fly proliferation and significantly reducing the pathogen load. This study reveals a drug that can used as an alternative application for mastitis in human or veterinary clinics.