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Escherichia coli (E.coli) found in retail chicken meat could be causing a wide range of infections in humans and constitute a potential risk. This study aimed to evaluate 60 E. coli isolates from retail chicken meat (n = 34) and human... more
Escherichia coli (E.coli) found in retail chicken meat could be causing a wide range of infections in humans and constitute a potential risk. This study aimed to evaluate 60 E. coli isolates from retail chicken meat (n = 34) and human urinary tract infections (UTIs, n = 26) for phylogenetic diversity, presence of pathogenicity island (PAI) markers, antimicrobial susceptibility phenotypes, and antimicrobial resistance genes, and to evaluate their biofilm formation capacity. In that context, confirmed E.coli isolates were subjected to phylogrouping analysis using triplex PCR, antimicrobial susceptibility testing using the Kirby–Bauer disc diffusion method; PAI distribution was investigated by using two multiplex PCRs. Most of the chicken isolates (22/34, 64.7%) were identified as commensal E. coli (A and B1), while 12 isolates (35.3%) were classified as pathogenic virulent E. coli (B2 and D). Similarly, the commensal group dominated in human isolates. Overall, 23 PAIs were detected in...
Animal-derived xenogeneic biomaterials utilized in different surgeries are promising for various applications in tissue engineering. However, tissue decellularization is necessary to attain a bioactive extracellular matrix (ECM) that can... more
Animal-derived xenogeneic biomaterials utilized in different surgeries are promising for various applications in tissue engineering. However, tissue decellularization is necessary to attain a bioactive extracellular matrix (ECM) that can be safely transplanted. The main objective of the present study is to assess the structural integrity, biocompatibility, and potential use of various acellular biomaterials for tissue engineering applications. Hence, a bovine pericardium (BP), porcine pericardium (PP), and porcine tunica vaginalis (PTV) were decellularized using a Trypsin, Triton X (TX), and sodium dodecyl sulfate (SDS) (Trypsin + TX + SDS) protocol. The results reveal effective elimination of the cellular antigens with preservation of the ECM integrity confirmed via staining and electron microscopy. The elasticity of the decellularized PP (DPP) was markedly (p < 0.0001) increased. The tensile strength of DBP, and DPP was not affected after decellularization. All decellularized t...
Despite its disadvantages, chemotherapy is still commonly used for the treatment of bladder cancer (BC). Developing natural supplements that can target cancer stem cells (CSCs) which cause drug resistance and distant metastasis is... more
Despite its disadvantages, chemotherapy is still commonly used for the treatment of bladder cancer (BC). Developing natural supplements that can target cancer stem cells (CSCs) which cause drug resistance and distant metastasis is necessary. Chaga mushrooms are popular to have several health-promoting and anti-cancer potentials. Organoid culture can recapitulate tumor heterogeneity, epithelial environment, and genetic and molecular imprints of the original tissues. In the previous study, we generated dog bladder cancer organoids (DBCO) as a novel experimental model of muscle-invasive BCO. Therefore, the present study aimed to examine the anti-tumor potentials of Chaga mushroom extract (Chaga) against DBCO. Four strains of DBCO were used in the present study. Treatment with Chaga inhibited the cell viability of DBCO in a concentration-dependent way. Treatment of DBCO with Chaga has significantly arrested its cell cycle and induced apoptosis. Expression of bladder CSC markers, CD44, C...
BackgroundThe intraventricular pressure difference (IVPD) and intraventricular pressure gradients (IVPG), estimated from color M-mode echocardiography (CMME) of the transmitral flow, have been introduced as novel indices for the... more
BackgroundThe intraventricular pressure difference (IVPD) and intraventricular pressure gradients (IVPG), estimated from color M-mode echocardiography (CMME) of the transmitral flow, have been introduced as novel indices for the evaluation of heart functions. Until now, no study demonstrated the feasibility of the CMME approach to measure IVPD and IVPG in any farm animals. The aim of this study was to assess the feasibility and repeatability of CMME-derived IVPD and IVPG variables in goats and explore the effect of sedation on the measured variables.Materials and methodsSixteen male Shiba goats were included in this study and underwent conventional echocardiography. Eight goats were used in the repeatability of IVPD/IVPG variables. Another eight goats were used to evaluate the effect of sedation by xylazine on IVPD/IVPG measurements. CMME between the base and the apex of the left ventricle was carried out. The IVPD and IVPG were analyzed using in-house code software. The IVPD and IV...
The present study aimed to investigate the prevalence, antibiotic susceptibility profiles, and some toxin genes of Panton-Valentine leukocidin (PVL)-positive Staphylococcus aureus (S. aureus) in unpasteurized raw cow’s milk collected from... more
The present study aimed to investigate the prevalence, antibiotic susceptibility profiles, and some toxin genes of Panton-Valentine leukocidin (PVL)-positive Staphylococcus aureus (S. aureus) in unpasteurized raw cow’s milk collected from retail outlets located at Mansoura, Dakahliya governorate, Egypt. In that context, a total of 700 raw cow’s milk samples were investigated for the presence of S. aureus, which was identified in 41.1% (288/700) of the samples. Among the S. aureus isolates, 113 PVL-positive S. aureus were identified and subjected for further analysis. The PVL-positive S. aureus were investigated for the existence of toxin-related genes, including hemolysin (hla), toxic shock syndrome toxin-1 (tst), and enterotoxins (sea, seb, sec, see, seg, sei, and selj). Genotypic resistance of PVL-positive strains was performed for the detection of blaZ and mecA genes. Among the PVL-positive S. aureus, sea, seb, and sec were detected in 44.2, 6.2%, and 0.9%, respectively, while th...
Copyright © 2014 Mohamed Aboubakr et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work... more
Copyright © 2014 Mohamed Aboubakr et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This study was designed to investigate the possible developmental teratogenicity of norfloxacin in rats. Forty pregnant female rats were divided into four equal groups. Group A received norfloxacin in a dose of 500mg/kg⋅b⋅wt/day orally from 6th to 15th day of gestation. Groups B and C received 1000 and 2000mg/kg⋅b⋅wt/day orally for the same period, respectively; Group D behaved as control and received 0.5mL distilled water orally for the same period. The dams were killed on 20th day of gestation and their fetuses were subjected to morphological, visceral, and skeletal examinations. Norfloxacin significantly decreased the number of viable fetuses, increased the number of resorbed fetuses, and induced retardation in growth of viable ...
The plant growth regulator gibberellic acid (GA3) is widely used in agriculture in many countries. However, little is known about its danger to human health or its physiologic and biochemical pathways. Our study examined the effect of GA3... more
The plant growth regulator gibberellic acid (GA3) is widely used in agriculture in many countries. However, little is known about its danger to human health or its physiologic and biochemical pathways. Our study examined the effect of GA3 on liver and kidney function and the effect of quercetin on the hepatorenal toxicity induced by GA3 in four groups of male albino rats. For 4 weeks, the control group (CNT) received saline, the quercetin group (QR) received daily intraperitoneal injections of quercetin (50 mg/kg/BW) dissolved in saline, the gibberellic acid group (GA3) received GA3 (55 mg/kg/BW) via oral gavage, and the protective group (QR) was injected with quercetin and gavaged with GA3 in the same doses used in the QR and GA3 groups (50 mg/kg/BW +GA3 and 55 mg/kg/BW). GA3 induced liver and kidney injury, as shown by elevated serum glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, and gamma-glutamyl transferase (GPT, GOT, and GGT) as well as increased levels of creatinine, urea, and uric acid. Hepatorenal toxicity was demonstrated by a significant increase in levels of serum and tissue malondialdehyde (MDA) and decreased antioxidant enzyme activity, such as catalase (CAT) and superoxide dismutase (SOD), accompanied by a subsequent decrease in glutathione peroxidase (GPx) levels in liver and kidney tissue of GA3-treated rats. Administration of quercetin (QR) significantly protected hepatorenal tissue against the toxic effect of GA3 through normalization of the hepatic and renal function markers. It also retrieved the antioxidant ability by modulating the hepatorenal toxic effect at the molecular level through upregulation of antiapoptotic genes and downregulation of transforming growth factor-β1 (TFG-β1), cyclooxygenase-2 (COX-2), and nuclear factor-kappa B (NF-κB). Impairment of liver and kidney function was confirmed by histologic and immunohistochemical analyses. Pretreatment with quercetin was effective at attenuating histopathologic changes in hepatic and renal tissues by regulating the immunoexpression of caspase-3 and Bcl-2 to return them to more normal values. PRACTICAL APPLICATIONS: The confirmed hepatorenal dysfunction caused by GA3 was ameliorated by quercetin administration. Moreover, quercetin demonstrated the potential to reverse hepatorenal dysfunction by regulating inflammatory and antioxidant properties, inhibiting the production of free radicals and inflammation-associated cytokines, and modulating antioxidants and antiapoptotic activity.
The pharmacokinetic parameters of cefadroxil (20 mg/kg bwt) were studied following single intravenous (IV) and oral (PO) administrations in healthy broiler chickens. Following a single IV injection of cefadroxil at a dose of 20 mg/kg bwt... more
The pharmacokinetic parameters of cefadroxil (20 mg/kg bwt) were studied following single intravenous (IV) and oral (PO) administrations in healthy broiler chickens. Following a single IV injection of cefadroxil at a dose of 20 mg/kg bwt in healthy chickens, cefadroxil could be detected therapeutically for 24 h. The serum concentration–time curve of cefadroxil following IV injection showed that, the drug obeyed a two compartments open model and the elimination half-life (t0.5β) was 4.85 h, volume of distribution (Vdss) was 629 ml/kg and total body clearance (CLtot) of cefadroxil was 0.185 L/h/kg). Following a single PO administration of 20 mg cefadroxil /kg bwt in healthy chickens, the peak serum concentration (Cmax) was 15.59 μg/ml was achieved at a maximum time (Tmax) of 1.47 h. The oral bioavailability of cefadroxil in healthy chickens was 77.18%.
The pharmacokinetics (after single oral, i.m. and i.v. administration) and tissue residues after repeated oral (daily for five days) and i.m. (daily for two days) administration of apramycin were investigated in healthy broiler chickens.... more
The pharmacokinetics (after single oral, i.m. and i.v. administration) and tissue residues after repeated oral (daily for five days) and i.m. (daily for two days) administration of apramycin were investigated in healthy broiler chickens. Apramycin was administered at a dose level of 25 mg/kg b. wt. (for oral and i.m. administration) and at 10 mg/kg b. wt. for i.v. injection. Seventy clinically healthy Hubbard chickens of 1.65~2 kg b.wt. and of 45 days old, were used in the current study. The maximum plasma concentrations of apramycin were achieved 0.18 and 0.70 h after oral and i.m. administration with an absorption half-life (t1/2ab.) of 0.11 and 0.18 h and an elimination half-life (t1/2β) of 1.23 and 2.33 h, respectively. The systemic bioavailability was 2.5 and 60.5 % after oral and i.m. administration, respectively, indicating poor oral absorption of apramycin. After i.v. injection, the pharmacokinetics of apramycin was best described by a two-compartment open model with a t1/2α...
The disposition kinetics and serum availability of amikacin in broiler chickens after single intravenous (IV) and intramuscular (IM) administrations of 10 mg/kg body weight were investigated. The concentrations of the drug in the serum... more
The disposition kinetics and serum availability of amikacin in broiler chickens after single intravenous (IV) and intramuscular (IM) administrations of 10 mg/kg body weight were investigated. The concentrations of the drug in the serum were measured using microbiological assay on samples collected at frequent intervals after drug administration. Following intravenous injection, the serum concentration-time curves were best described by a two compartment open model. The elimination half-life (t1/2β), volume of distribution at steady state (Vdss) and total body clearance (Cltot) of amikacin were 4.48 h, 501.03 ml/kg and 0.08 L/h/kg, respectively. After intramuscular injection of amikacin at the same dose the peak serum concentrations (Cmax) were 15.25 μg/ml and were obtained at 1.89 h (tmax), the elimination half-life (t1/2el) were 5.23 h and absorbtion half-life (t1/2ab) were 0.75 h. The systemic bioavailability was 95.20%. Amikacin was detected in liver and kidney for 5 days post a ...
Despite its adverse effects, chemotherapy is generally used for the treatment of colorectal cancer (CRC). Development of supplement preparations targeting cancer stem cells (CSCs) that cause distant metastasis and drug resistance is... more
Despite its adverse effects, chemotherapy is generally used for the treatment of colorectal cancer (CRC). Development of supplement preparations targeting cancer stem cells (CSCs) that cause distant metastasis and drug resistance is required. Although curcumin is known to have anti-tumor, hepatoprotective, and hypoglycemic-like actions, its low water solubility, oral absorption, and bioavailability impede its therapeutic uses. Patient-derived organoid cultures can recapitulate heterogeneity, epithelial structures, and molecular imprints of their parental tissues. In the present study, anti-carcinogenic properties of amorphous curcumin (AC), a compound with improved solubility and bioavailability, were evaluated against human CRC organoids. Treatment with AC inhibited the cell viability of CRC organoids in a concentration-dependent manner. AC arrested the cell cycle of CRC organoids and induced apoptosis. AC inhibited phosphorylation of ERK. Expression of downstream signals of ERK, namely c-MYC and cyclin-D1, were inhibited. Expressions of CSC markers, CD44, LGR5, and CD133, were declined in the AC-treated CRC organoids. The combinational treatment of CRC organoids with AC and anti-cancer drugs, oxaliplatin, 5-FU, or irinotecan showed a synergistic activity. In vivo, AC decreased the tumor growth of CRC organoids in mice with the induction of necrotic lesions. In conclusion, AC diminished the cell viability of CRC organoids through the inhibition of proliferation-related signals and CSC marker expression in addition to arresting the cell cycle. Collectively, these data suggest the value of AC as a promising supplement that could be used in combination with anti-cancer drugs to prevent the recurrence and metastasis of CRC.
Death associated protein kinase (DAPK) is a calcium/calmodulin-regulated serine/threonine kinase; its main function is to regulate cell death. DAPK family proteins consist of DAPK1, DAPK2, DAPK3, DAPK-related apoptosis-inducing protein... more
Death associated protein kinase (DAPK) is a calcium/calmodulin-regulated serine/threonine kinase; its main function is to regulate cell death. DAPK family proteins consist of DAPK1, DAPK2, DAPK3, DAPK-related apoptosis-inducing protein kinases (DRAK)-1 and DRAK-2. In this review, we discuss the roles and regulatory mechanisms of DAPK family members and their relevance to diseases. Furthermore, a special focus is given to several reports describing cross-talks between DAPKs and mitogen-activated protein kinases (MAPK) family members in various pathologies. We also discuss small molecule inhibitors of DAPKs and their potential as therapeutic targets against human diseases.
Background: The present study was conducted to evaluate the efficacy of lincomycin and/or bacitracin for control of experimentally-induced Clostridium perfringens (CP) infection in broiler chickens.Methods: A total of 100 one-day-old... more
Background: The present study was conducted to evaluate the efficacy of lincomycin and/or bacitracin for control of experimentally-induced Clostridium perfringens (CP) infection in broiler chickens.Methods: A total of 100 one-day-old Cobb-mixed chicks were divided into five groups (A, B, C, D and E, each of 20 bird). At the 15th day of age, all birds (except group A) were inoculated orally with CP broth culture (109 CFU/mL). Two days later, drugs were orally administered once daily for five consecutive days as follow; Group A and B were left untreated. Group C, D, and E were treated with lincomycin (0.5 g/l), bacitracin (100 mg/l), lincomycin and bacitracin, respectively. The efficacy of used drugs was estimated based on clinical symptoms, body weight, weight gain, feed conversion rate. Hematobiochemical changes were also determined.Results: Necrotic enteritis in broiler chickens induced a significant decrease in body weight, weight gain, erythrocytic count, hemoglobin content, PCV ...
Multidrug resistance-associated protein 1 (MRP1) is a cysteinyl leukotriene (CysLT) export pump expressed on mast cells. CysLTs are crucial mediators in allergic airway disease. However, biological significance of MRP1 in allergic airway... more
Multidrug resistance-associated protein 1 (MRP1) is a cysteinyl leukotriene (CysLT) export pump expressed on mast cells. CysLTs are crucial mediators in allergic airway disease. However, biological significance of MRP1 in allergic airway inflammation has not yet been elucidated. In this study, we sensitized wild-type control mice ( mrp1+/+) and MRP1-deficient mice ( mrp1−/−) to ovalbumin (OVA) and challenged them with OVA by aerosol. Airway inflammation and goblet cell hyperplasia after OVA exposure were reduced in mrp1−/− mice compared with mrp1+/+ mice. Furthermore, CysLT levels in bronchoalveolar lavage fluid (BALF) from OVA-exposed mrp1−/− mice were significantly lower than those from OVA-exposed mrp1+/+ mice. Levels of OVA-specific IgE, IL-4, and IL-13 in BALF were also decreased in OVA-exposed mrp1−/− mice. IgE-mediated release of CysLTs from murine bone marrow-derived mast cells was markedly impaired by MRP1 deficiency. Our results indicate that MRP1 plays an important role i...
Objectives: To evaluate the adverse effects of amoxicillin and doxycycline On liver and kidney functions of rats. Material and methods: Twenty-seven male wister albino rats were used and divided randomly into 3 groups’ each of 9 rats.... more
Objectives: To evaluate the adverse effects of amoxicillin and doxycycline On liver and kidney functions of rats. Material and methods: Twenty-seven male wister albino rats were used and divided randomly into 3 groups’ each of 9 rats. Group (1): were served as control and administered 0.5 ml saline orally for 5 consecutive days. Group (2): were served as amoxicillin group and administered 50 mg/kg amoxicillin trihydrate orally for 5 consecutive days. Group (3): were served as doxycycline group and administered 18 mg/kg body weight doxycycline hyclate orally for 5 consecutive days. Results: Amoxicillin induced significant increases in serum AST, ALT, direct bilirubin, total protein, creatinine and urea levels. Serum of doxycycline treated rats showed significant increases in serum AST, ALT, total protein and urea levels. Histopathological investigations were further supported the biochemical data of adverse effects on liver and kidney. On conclusion; amoxicillin or doxycycline induce...
The present study was conducted to evaluate the analgesic potential of the new triamilide macrolide antibiotic, tulathromycin, at 20 and 40 mg/kg of body weight (BW), subcutaneously against acute pain in mice. Acute pain was induced... more
The present study was conducted to evaluate the analgesic potential of the new triamilide macrolide antibiotic, tulathromycin, at 20 and 40 mg/kg of body weight (BW), subcutaneously against acute pain in mice. Acute pain was induced either chemically (using acetic acid-induced writhing and formalin-induced pain tests) or thermally (using hot-plate, and tail-flick tests). In the acetic acid-induced writhing test, tulathromycin induced a dose-dependent and significant decrease in the number of writhes compared with the control group. In the late phase of the formalin test, a significant decline in hind paw licking time compared with the control group was observed. In the hot-plate and tail-flick tests, tulathromycin caused a dose-dependent and significant prolongation of latency of nociceptive response to heat stimuli, compared with the control group. These findings may indicate that tulathromycin possesses significant peripheral and central analgesic potentials that may be valuable i...
The bioavailability and pharmacokinetics in turkeys of cefquinome (CFQ), a broad-spectrum 4th-generation cephalosporin antibiotic, were explored after a single injection of 2 mg/kg body weight by intravenous (IV) and intramuscular (IM)... more
The bioavailability and pharmacokinetics in turkeys of cefquinome (CFQ), a broad-spectrum 4th-generation cephalosporin antibiotic, were explored after a single injection of 2 mg/kg body weight by intravenous (IV) and intramuscular (IM) routes. In a crossover design and 3-weeks washout interval, seven turkeys were assigned for this objective. Blood samples were collected prior to and at various time intervals following each administration. The concentration of CFQ in plasma was measured using HPLC with a UV detector set at 266 nm. For pharmacokinetic analysis, non-compartmental methods have been applied. Following IV administration, the elimination half-life (t1/2ʎz), distribution volume at steady state (Vdss), and total body clearance (Cltot) of CFQ were 1.55 h, 0.54 L/kg, and 0.32 L/h/kg, respectively. Following the IM administration, CFQ was speedily absorbed with an absorption half-life (t1/2ab) of 0.25 h, a maximum plasma concentration (Cmax) of 2.71 μg/mL, attained (Tmax) at 0....
In patients with solid tumors, circulating tumor cells (CTCs) spread in their blood and function as a seed for metastases. However, the study of CTCs has been limited by their rarity, low frequency, and heterogeneity. The efficient... more
In patients with solid tumors, circulating tumor cells (CTCs) spread in their blood and function as a seed for metastases. However, the study of CTCs has been limited by their rarity, low frequency, and heterogeneity. The efficient collection of CTCs will contribute to further research of metastatic cancers. Apheresis is a process in which the whole blood of an individual is passed through a machine that isolates a particular constituent and returns the remainder to the circulation. In the present study, we investigated the safety and feasibility of apheresis to separate peripheral blood monocytes (PBMCs), whose density is closely similar to that of CTCs, and to capture intravenously administered human breast cancer cells, MCF7s, from the dogs. No life-threatening events were observed in dogs during the apheresis process. The changes in the hemogram were transient and recovered gradually within a few days after apheresis. During apheresis, 50 mL of PBMCs could be collected from each...
Three-dimensional (3D) organoid culture holds great promises in cancer precision medicine. However, Matrigel and stem cell-stimulating supplements are necessary for culturing 3D organoid cells. It costs a lot of money and consumes more... more
Three-dimensional (3D) organoid culture holds great promises in cancer precision medicine. However, Matrigel and stem cell-stimulating supplements are necessary for culturing 3D organoid cells. It costs a lot of money and consumes more time and effort compared with 2D cultured cells. Therefore, the establishment of cheaper and Matrigel-free organoid culture that can maintain the characteristics of a part of 3D organoids is demanded. In the previous study, we established a dog bladder cancer (BC) 3D organoid culture system by using their urine samples. Here, we successfully isolated cells named “2.5D organoid” from multiple strains of dog BC 3D organoids using 2.5 organoid media. The cell proliferation speed of 2.5D organoids was faster than parental 3D organoid cells. The expression pattern of stem cell markers was close to 3D organoids. Injection of 2.5D organoid cells into immunodeficient mice formed tumors and showed the histopathological characteristics of urothelial carcinoma s...
Bladder cancer (BC) is a complex and highly heterogeneous stem cell disease associated with high morbidity and mortality rates if it is not treated properly. Early diagnosis with personalized therapy and regular follow-up are the keys to... more
Bladder cancer (BC) is a complex and highly heterogeneous stem cell disease associated with high morbidity and mortality rates if it is not treated properly. Early diagnosis with personalized therapy and regular follow-up are the keys to a successful outcome. Cancer stem cells (CSCs) are the leading power behind tumor growth, with the ability of self-renewal, metastasis, and resistance to conventional chemotherapy. The fast-developing CSC field with robust genome-wide screening methods has found a platform for establishing more reliable therapies to target tumor-initiating cell populations. However, the high heterogeneity of the CSCs in BC disease remains a large issue. Therefore, in the present review, we discuss the various types of bladder CSC heterogeneity, important regulatory pathways, roles in tumor progression and tumorigenesis, and the experimental culture models. Finally, we describe the current stem cell-based therapies for BC disease.
Myc is a nuclear transcription factor that mainly regulates cell growth, cell cycle, metabolism, and survival. Myc family proteins contain c-Myc, n-Myc, and l-Myc. Among them, c-Myc can become a promising therapeutic target molecule in... more
Myc is a nuclear transcription factor that mainly regulates cell growth, cell cycle, metabolism, and survival. Myc family proteins contain c-Myc, n-Myc, and l-Myc. Among them, c-Myc can become a promising therapeutic target molecule in cancer. Cancer stem cells (CSCs) are known to be responsible for the therapeutic resistance. In the previous study, we demonstrated that c-Myc mediates drug resistance of colorectal CSCs using a patient-derived primary three-dimensional (3D) organoid culture. In this review, we mainly focus on the roles of c-Myc-related signaling in the regulation of CSCs, chemotherapy resistance, and colorectal cancer organoids. Finally, we introduce the various types of c-Myc inhibitors and propose the possibility of c-Myc as a therapeutic target against colorectal cancer.
Background: Pharmacokinetic study of a commercial tylosin-doxycycline combination product (D-Tylo50/25®) was conducted in broiler chickens following intravenous (IV) and oral (PO) administration at doses of 50 mg/kgb. wt. (tylosin) and 25... more
Background: Pharmacokinetic study of a commercial tylosin-doxycycline combination product (D-Tylo50/25®) was conducted in broiler chickens following intravenous (IV) and oral (PO) administration at doses of 50 mg/kgb. wt. (tylosin) and 25 mg/kg b. wt. (doxycycline).Methods: Serum drug concentrations were determined by a validated high performance liquid chromatography (HPLC) using UV detection.Results: A rapid and nearly complete absorption of both drugs with a mean PO bioavailability of 89.16% (tylosin) and 94.30% (doxycycline), prolonged elimination half-lives, and high tissue penetration with steady state volume of distribution of 6.73L/kg (tylosin) and 5.51L/kg (doxycycline) were observed. Tissue residues were studied following oral administration of each drug alone for fiveconsecutive days and blood and tissue samples were obtained for 10 days after the last dose. Residues of tylosin and doxycyclines showed that kidney, liver and lung contained highest drug residues and complet...
The aim of present study was to determine the pharmacokinetics and tissue residues of tilmicosin phosphate (tilmicoral®) as well as its in vitro and in vivo evaluation for control of Mycoplasma gallisepticum (MG) infection in broiler... more
The aim of present study was to determine the pharmacokinetics and tissue residues of tilmicosin phosphate (tilmicoral®) as well as its in vitro and in vivo evaluation for control of Mycoplasma gallisepticum (MG) infection in broiler chickens. Pharmacokinetics (single oral dose) and tissues residues (daily for five days) of tilmicosin (25 mg/kg b.wt) in broilers were investigated. Peak plasma concentration of tilmicosin was 1.25±0.0.09 μg/mL and achieved at 3.15±0.34 h. Elimination half-life was long (44.3±7.22 h) and Vdarea was large (1.25±0.082 L/kg). Residue study revealed a good distribution and penetration of tilmicosine in lung, liver, kidney and muscles. Tilmicosin could not be detected in all tested tissues (except in lung) at 6 days after last administration. The MIC of tilmicosin and tylosin against MG were 0.054 and 0.319 μg/mL, respectively. MG infected chickens and treated by tilmicosin or tylosin showed a significant (p<0.05) improvement in mean body weights gain an...

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Overexpression of nonsespecific active efflux pumps in Gram-negative bacteria, is an ubiquitous multidrug resistance (MDR) mechanism. There is increasing evidence that RND efflux pumps, as acrAB-TolC in Escherichia coli plays an important... more
Overexpression of nonsespecific active efflux pumps in Gram-negative bacteria, is an ubiquitous multidrug resistance (MDR) mechanism. There is increasing evidence that RND efflux pumps, as acrAB-TolC in Escherichia coli plays an important role in virulence expression by Gram-negative pathogens 1. The design of new therapeutic strategies such as inactivation of efflux pump systems by inhibitor drugs is a possible alternative to face the problem 2. The aim of our study was to evaluate the effect of the pump inhibitor 1-(1-naphthylmethylpiperazine)-NMP-in association with florfenicol (FLF), tetracycline (TET) and ciprofloxacin (CIP) against isogenic E. coli MDR phenotype, by time killing curves. The time-kill method of synergy testing was performed by the broth macrodilution technique 3. Two isogenic E. coli bacteria with known genotype were used: AG112 strain (overexpress-ing RND type efflux pumps), and AG100 (wild type). The anti-microbials tested were FLF, TET, CIP. Three groups of five LB broth tubes were used for each antimicrobial tested. In the first one, the time-killing curve was determined against the antimi-crobial alone. In the second and the third groups, the antibiotic was combined with 50 and 100 lg ml À1 of the efflux pump inhibitor respectively. Antimicrobial concentrations evaluated were the CIM, 2, 4 and 8 times the MIC; and a fifth tube without antimicrobial, as control. Duplicate samples from every tube were obtained at 0, 2, 4, 8, 24 and 48 h after incubation for 24 h at 37°C, and colony counts were determined. The activity of the antimicrobials alone and in combination was determined by plotting Log 10 colony counts (CFU ml À1) against time. The results were corroborated by statistical analysis (ANOVA). No significant differences (P < 0.05) were found in the effectiveness percentage of antimicrobial alone or with NMP (50 lg ml À1 or 100 lg ml À1). Nevertheless, antimicrobial concentrations assayed were 4 to 16 times lower with NMP (50 lg ml À1 or 100 lg ml À1 respectively), than in the group of tubes without the efflux pump inhibitor. These results mean that it was possible to preserve the kinetics of death in the group of tubes with NMP (50 lg ml À1 or 100 lg ml À1). The use of NMP is promising; it may be possible not only to change bacterial susceptibility, but also to infer the abilities of bacteria to successfully infect the host. Experimentally-induced colibacillosis in piglets: effect of age and size of the inoculum O. ROY CEBIPHAR, Fondettes, France Colibacillosis is a severe disease in pigs with outbreaks occurring at weaning worldwide that cause fatal diarrhea. Two infectious models were developed, differing by the age of piglets at inoculation and the inoculum size. A first model using piglets just after weaning was previously developed and a new model with older animals has been implemented. Post-weaning diarrhoea was induced in conventional piglets by administrating on two consecutive days an Escherichia coli K88 strain. Administration of the inoculum via a gastric feeding probe was preceded by drenching of tryptic soy broth containing 1.2% bicarbonate. Piglets were randomly allocated according to body weight and sex to four groups. The animals were inoculated within 1 week or 2 weeks after weaning using different sizes of inoculum (log9 or log10 CFU) at each age depending on groups. The animals were clinically examined daily for 2 weeks. Clinical examination included rectal temperatures and scoring of general and digestive clinical signs. Body weight and feed intake were measured. Fecal samples were taken for total E. coli and haemolytic E. coli flora enumeration. The animals were euthanized 2 weeks after inoculation and gross examination of the gastro-intestinal track was conducted. Inoculation produced characteristic clinical signs of colibacillo-sis within 1 day whatever the age at inoculation and the size of the inoculum. Abnormal faeces were frequently observed the days following the inoculation, mainly during the first week in all groups, and progressively decreased thereafter. Severity of clinical signs was higher in younger animals but did not differ significantly between groups. Mortality remained limited and occurred shortly after the inoculation. Time courses of mean faecal total and haemolytic counts were similar between groups and showed an increase of the counts just after the challenge and return to basal values the week after for the total counts. No obvious gross lesions were observed at nec-ropsy 2 weeks after the challenge. Both models succeeded in producing a stable clinical colibacil-losis. The age at inoculation and the size of the inoculum did not significantly impact the outcome of this model. Inoculation of piglets 2 weeks after weaning allow a sufficient time period for possible preventive treatment before challenge in experimental efficacy studies. † The text was changed following initial online publication. 84