p. 5 p. 6 1 p. 11 1. p. 12 2. 1) p. 14 2) p. 14 3) p. 14 4) p. 15 3. p. 16 4. p. 17 5. p. 20
1. p. 23 2. p. 25 1) BRDC p. 25 2) BRDC p. 25 3. p. 28 1) BRDC p. 28 2) BRDC p. 28 4. p. 30 5. p. 32 3 p. 36 1. p. 37 2. p. 38
2) p. 38 3) p. 38 4) p. 38 5) p. 39 6) p. 41 3. p. 42 4. p. 43 5. p. 45 p. 48 p. 52 p. 56 p. 60 p. 62
BAL Bronchoalveolar lavage BALF Bronchoalveolar lavage fluid
BRDC Bovine Respiratory Disease Complex BUN Blood Urea Nitrogen
ELF Epithelial lining fluid Glu Glucose
Hct Hematocrit
HDL-Cho High-density lipoprotein cholesterol Hgb Hemoglobin
MBFX Marbofloxacin
MCH Mean Corpuscular Hemoglobin Mg Magnesium
MIC Minimum Inhibitory Concentration
NEFA Non-Esterified Fatty Acid
RBC Red Blood Cell
SD Standard Deviation
TBA Tracheobronchial aspirate T-Cho Total Cholesterol
1995 2018 1974 53 2200 1 2018 52 [41] 2 10 3 10 2 F1 Gonzalez [14, 50]
[49] [14] [17, 52] 2017 6 13,502 6,982 52 [26] 887 179 20 [26] 2014 4 1 2018 3 31 1,603 30 865 54
MBFX 2010 [16, 35, 56] MBFX [16, 35, 56] MBFX [7] MBFX [3, 6, 34] 3
1
2
1. 2014 57,500 2,567,000 43.8% 26.8% . 35.9 % 19.9 % 11.6 % [40] 2014 7 13,357 11,113 43.1 % 35.8 % [37] [59] [14, 38, 50, 61] [1, 14, 58, 61] [14] . [58]
2. 1 2013 10 1 10 472 295 ± 20 275 ± 29 kg 1 DG 0.8 ± 0.1 kg/ 305 ± 14 284 ± 30 kg DG 0.8 ± 0.1 kg / 2 2,078 km 1,130 km 948 km 62 1 3 D1052 10 14 10 17 10 18 1 VP-NA052K VP-P070K30
MCH Alb
T-Cho (BUN) Glu NEFA
AST -A Vit. -A Mg - HDL HDL-Cho LDL [9] 4 ± Student-5
3.
283.5 ± 29.6 kg 256.2 ± 26.5 kg 9.6 ± 1.3 % 7.0~11.0 %
RBC, Hgb , Hct MCH
NEFA < 0.05 T-Cho BUN Glu
AST Vit. A Mg HDL-Cho < 0.05
[14, 38, 50] Warriss 5 4.6 10 6.5 15 7.0 [61] Gonzalez 400 km 7.94 6.13 [14] 0.30 1.52 [38] 1.4 1.2 [50] 25 2.6 [58] [23] [14] 2,078 km 62 RBC Hgb Hct MCH [14] NEFA 0.15 [25] 0.5 ± NEFA [58]
NEFA
[53]
NEFA [42]
T-Cho HDL-Cho . T-Cho
[27] T-Cho BUN Gul Glu [59] Glu AST DMI AST [21] DMI Mg Mg [28] Vit. A [1] Vit. A 2,000 km 60
5. 10 2,078 km 1,130 km 948 km 62 283.5 ± 29.6 kg ± 256.2 ± 26.5 kg < 0.001 9.6 ± 1.3 % 7.0 11.0 % 10 , , , A HDL < 0.05
Bovine Respiratory Disease Complex : BRDC .
BRDC
[11 52] BRDC
X CT
Bronchoalveolar lavage : BAL
BAL Bronchoalveolar lavage fluid : BALF Tracheobronchial aspirate : TBA
[19, 20, 24]
[12] BRDC [29, 31, 32, 48] BRDC [4, 5, 39] BRDC BAL BRDC BAL BRDC
1 2011 11 2013 3 3 5 6 8 9 11 12 2 ± 2 BRDC BRDC 2013 12 15 39.7 3 3 2014 3 33 39.7 3 5 C 0.5 7 9 TBA BALF [9]
VP-DK052K pocH-100iV Diff, BD BBL BALF OLYMPUS VQ TYPE 5112B . 2 % 37 30 ml 2 BALF BALF BAL 37 30 ml
TBA TBA BALF TBA
300 l TBA BALF 5 % BA MAC BA 2 37 5 % CO2 MAC 1 37 24 BA Time of Flight Mass Spectrometry MALDI-TOF/MS
37 5 % CO2 3 7
1 NK
7 MALDI-TOF/MS
LAMP Loop-Mediated Isothermal Amplification [15] .
3. 1 BRDC 12 23 408 2012 10 3 32 2013 3 17 7 2 64 18 3 15.2 % 2 2012 2 24 3 19 8 2011 11 12 2012 8 21 2 1 2012 2 24 42.1 % 134 33 76 165 [ 1] 2 13.2 % 8.8 6.2 % 22.3 % 2 8.0 ± 3.1 11.0 ± 0.0 12.2 ± 0.6 9.5 ± 3.0 [ 1] 2 BRDC 2013 12 3 1 13,600 counts / l
2013 12 3 BALF 1 :
No. 1 1 No. 2 1 No. 3 [
3] 3 BALF 1 No. 4
TBA 1 :
No.1 2 : No. 2, 3 BALF
1 No.4 TBA 1 No.3 1 3 TBA BALF [ 2] 2014 3 3 BALF 1
No. 3 1 No. 1 BALF
1 No. 6 TBA 1 : No. 3 1 No. 1 2 No. 5, 8 4 No. 4-6, 8 1 No. 3 4 No. 4, 6-8 1 No. 7 1 No. 3 2 No. 4, 8 3
4. BRDC BAL BRDC TBA BALF BRDC [30] [43] [22] [4, 5] 2013 12 BAL 1 3 2014 3 BALF BALF 2 BRDC
[55]
0.5
7 9
5. 2013 2014 408 2 64 15.7 % 2013 6 1 . 2014 8 1 . .
[45, 46] [16, 56] [45, 46] MBFX 2010 [16, 35, 56] [16, 35, 56] MBFX [7] [3, 6, 34] MBFX BALF MBFX
2. 1) 4 2 1 4 53.9 2.9kg 50.5 57.5 kg 2 6 70.5 5.8 kg 62.5 76.5 kg 2) MBFX 2 mg/kg B.W. ®10 % Meiji Seika VP-H100K VP-NA052K EDTA-2AK 1 2 6 24 BALF 2 3) EDTA-2AK Poch-100iV WBC RBC Hgb HCT 30 80 Quantichrom
4) BAL VQ TYPE 6112B 5.5 mm, 1.1m 0 1 2 6 24 2 % 37 0.9 % 30 ml BALF 2 1
2 BAL BALF BAL
3 6 3 5 5 2 3 5 BALF . BALF 400 5 4 BALF 30 ml BALF BALF
MRFX De Baere [8] 10 BALF 0.5 ml 1 mol 1.0 ml 3 300 l BALF BALF 60 l 1 / 300 ng / ml 4 1 60 l 350 l Oasis HLB Waters 250 l
10 l High performance liquid chromatography HPLC; Prominence
MBFX ELF BALF [12, 14]
ELF MBFXELF MBFX
ELF = /
ELF MBFX =BALF MBFX /BALF
BALF MBFX
BALF
MBFXAC MBFX
BALF MBFX 1.28 l / 106 BALF
[13, 15] MBFX 24 - 0-24
Area under the curve AUC0-24 Wang
[60] 1 2
6)
Tukey-Kramer 3 MBFX
IBM SPSS Statistics 24 IBM 5
3. WBC RBC Hgb HCT MBFX MBFX 2.02 g/ml 2 2.04 g/ml 6 1.25 g/ml 24 0.27 g/ml [ 1] ELF MBFX MBFX 2.37 g/ml 2 3.42 g/ml 6 1.76 g/ml 24 0.39 g/ml MBFX MBFX 1.71 g/ml 2 2.02 g/ml 6 1.23 g/ml 24 0.37 g/mll ELF MBFX MBFX MBFX 2 1.7 0.05 ELF AUC0-24 21.3 32.6 23.0 g-hr / ml [ 1] ELF AUC0-24 AUC0-24 0.05
BALF MBFX MBFX
ELF MBFX AUC0-24 AUC0-24
MBFX (MIC) [33] , , MBFX MIC90 0.12 0.25 0.06 2.00 g/ml [33] MBFX
[51, 62] AUC0-24 MIC AUC / MIC
[47, 51, 57]
AUC / MIC 100 125 [2, 10, 51, 57, 62]
ELF AUC / MIC
AUC / MIC 125 ELF AUC / MIC
AUC / MIC 100
MBFX
MBFX MBFX
4 MBFX 2 mg/kg 1 2 6 24 MBFX 2 MBFX ELF MBFX BALF MBFX BALF 2 ELF MBFX BALF 0.05 0 24 MBFX ELF MBFX 0.05 MBFX
A HDL 2 BRDC BAL BRDC 2014 8 1 3 ELF BALF MBFX MBFX 2 BALF MBFX
283.5 29.6 kg 256.2
26.5 kg 0.001
A HDL 0.05 408 2 64 2013 6 1 . 2014 8 1 . . MBFX 4 MBFX 2 mg/kg 1 2 6 24 MBFX 2 2 ELF MBFX BALF
capability to eliminate pathogens from the body and disrupt its immune system. Although changes in feed and feeding environment, weaning, dehorning, and herd round-up and dispersal are often among the first factors to be cited, transportation has the potential to be a major extrinsic factor affecting cows physically. Cattle being transported for introduction to a new farm are thus clearly an important population for research on BRD pathology. Furthermore, the selection and use of antibacterial agents targeting BRD also necessitate careful attention, and should be determined based on a sufficient body of evidence.
Accordingly, in this study, we set out to investigate the physical (Experiment-1) and BRD-related (Experiment-2) effects of transportation on field-grazed cattle being introduced to a new farm, and distribution of an anti-bacterial agent to the bronchoalveolar region (Experiment-3). Experiment-1 involved a focus on cattle undergoing long-range transportation. Experiment-2 involved determining the post-introduction BRD rate, and testing transported cattle for BRD-inducing bacteria with analysis of bronchoalveolar lavage fluid (BALF) obtained by bronchoendoscopy. Experiment-3 involved investigating the pharmacokinetics of marbofloxacin, a fluoroquinolone antibacterial drug that has been approved for use in livestock and has been widely used clinically in recent years.
In Experiment-1, we targeted ten Japanese Black heifers transported 2,078 km (1,130 km by road and 947 km by ferry) from Miyazaki to Hokkaido over 62 hours on a cattle transport vehicle, for measurements of body weight and hematological and serum biochemical parameters. Post-transportation, the cows showed
283.5 ± 29.6 kg vs. 256.2 ± 26.5 kg (p<0.001); mean increase: 9.6%)], and significantly increased red blood cell count, hemoglobin, hematocrit, mean corpuscular hemoglobin, and serum nonesterified fatty acid (p<0.05). Conversely, these cows showed significantly decreased serum levels of total cholesterol, blood urea nitrogen, glucose, aspartate aminotransferase, vitamin A, magnesium, and high-density lipoprotein cholesterol (p<0.05). These findings indicate insufficient nutrient intake and dehydration. Accordingly, we suggest that decreased body weight after transportation could be related to decreased dry matter and water intakes.
In Experiment 2, we targeted 488 head of fattening cattle introduced to a farm after purchase at market between 2011 and 2013 for an investigation of BRD morbidity and treatment (based on treatment records, and bacteriological analysis of BALF, tracheal lavage fluid, and nasal swabs). Sixty-four animals required treatment for BRD in the two weeks following introduction to the farm, and were designated as febrile; the other animals were designated as non-febrile controls. The number of cows requiring treatment tended to be greater in winter, and the time to symptom onset (number of days) was shorter in spring. Bacteriological examinations revealed BRD pathogens
( ), and/or in all febrile steers, but in only one non-febrile control (that showed cough and runny nose and had ) in December 2013. Further examinations in March 2014 revealed or in some febrile steers, but in only one non-febrile steer. All samples were negative for . We demonstrated the presence of pneumonia-inducing microbes in the bronchoalveolar region of cattle that developed post-transportation BRD, illustrating the importance of prevention and treatment measures for steers
distribution of of the drug to the bronchoalveolar region. Plasma and BALF samples were obtained for each calf at 0 (before administration), and 1, 2, 6 and 24 hr after injection of MBFX. The injection-and-sample-collection procedure was repeated after two weeks. MBFX concentrations were significantly higher in pulmonary epithelial lining fluid (ELF) than in plasma and alveolar cells at 2 hr after injection (p<0.05). The mean area under the MBFX concentration vs time (0 to 24 hr) curve (AUC0-24) was significantly greater for pulmonary ELF than plasma (p<0.05). Our
findings suggest that intramusculary injected MBFX was well distributed to the bronchoalveolar region.
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