Pharmacokinetics, tissue residues and efficacy of D-Tylo50/25® (tylosin-doxycycline combination) in broiler chickens

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 completely disappeared from those tissues at 5 and 6 days after the last oral dose, respectively. The efficacies of D-Tylo50/25® and other antibiotics (tiamulin and oxytetracyline) were investigated in broiler chicks experimentally infected by Mycoplasma gallisepticum.Conclusions: The pharmacokinetics of both drugs was characterized by a rapid and complete absorption, extensive tissue distribution and slow elimination. D-Tylo50/25® is more effective than tiamulin and oxytetracycline against Mycoplasma gallisepticum infection in broilers

Bioequivalence study of two oral amoxicillin formulations (Biocillin® and Atcomox 87%®) in broiler chickens

Background: The present study was designed to assess the comparative bioequivalence of Biocillin® and Atcomox87%® in healthy broiler chickens after oral administration of both products in a dose of 20 mg amoxicillin base/kg.b.wt.Methods: Twenty-four broiler chickens were divided into two groups. The first group was designed to study the pharmacokinetics of Biocillin®, while the 2nd group was designed to study the pharmacokinetics of Atcomox87%®. Each broiler chicken in both groups was injected intravenously with 20 mg amoxicillin pure standard/kg.b.wt. After 15 days both groups taken orally Biocillin® and Atcomox87%®, respectively. Blood samples were obtained from the wing vein and collected immediately before and at 0.08, 0.16, 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours after a single intravenous or oral administration.Results: Amoxicillin in both products obeyed a two compartments open model following I.V. injection. The disposition kinetics of Biocillin® and Atcomox87%® following oral administration of 20 mg amoxicillin base/kg.b.wt. revealed that the maximum blood concentration [Cmax] were 10.79 and 10.30 μg/ml and attained at [tmax] of 0.90 and 0.86 hours, respectively. The mean systemic bioavailability of amoxicillin in Biocillin® and Atcomox 87%® after oral administration in healthy chickens was 64.15 and 65.54%, respectively.Conclusions: Atcomox 87%® is bioequivalent to Biocillin® since the ratios of Cmax, AUC0-24 and AUC0-∞ (T/R) were 0.95, 0.91 and 0.90 respectively. These are within the bioequivalence acceptance range. Biocillin® and Atcomox87%® are therefore bioequivalent and interchangeable

Chemosensitivity of three patient-derived primary cultures of canine pericardial mesothelioma by single-agent and combination treatment

IntroductionCanine mesothelioma is a rare malignant tumor that mostly affects body cavities, such as the pericardial and pleural cavities. Chemotherapy plays a crucial role in the treatment of canine mesotheliomas. We aimed to compare the antitumor effects of single-agent and combination chemotherapeutic agents on patient-derived primary cultures of canine pericardial mesothelioma established in this study. We planned to generate xenograft models for future studies.Material and methodsEffusion samples were collected from three dogs with histologically diagnosed pericardial mesothelioma and used for primary culture. Cultured cells were characterized by immunostaining for pan-cytokeratin AE1/AE3, vimentin, Wilms' tumor suppressor gene 1 (WT1), and cytokeratin 5 (CK5). To assess the tumorigenic properties of cells in the effusion and generate a xenograft model, the cell suspension was injected into a severe combined immunodeficient (SCID) mouse either subcutaneously (SC) or intraperitoneally (IP). Lastly, chemosensitivity of established primary cultures against four drugs, doxorubicin, vinorelbine, carboplatin, and gemcitabine, by single-agent treatment as well as combination treatment of carboplatin at a fixed concentration, either 10 or 100 μM, and gemcitabine at different concentrations ranging from 0–1000 μM was assessed by cell viability assay.ResultsPrimary cultures were successfully generated and characterized by dual positivity for AE1/AE3 and vimentin and positive staining for WT-1 and CK5, confirming the mesothelial origin of the cells. In the xenograft models, SC mouse developed a subcutaneous mass, whereas IP mouse developed multiple intraperitoneal nodules. The masses were histopathologically consistent with mesotheliomas. The chemosensitivity assay revealed that carboplatin had the highest anti-tumor effects among the four tested single-agent treatments. Furthermore, carboplatin at 100 μM combined with gemcitabine at clinically relevant doses demonstrated the augmented anti-tumor effects compared to single-agent treatment.Discussion and conclusionPrimary cultures and xenograft models generated in this study could be useful tools for in vitro and in vivo studies of canine mesothelioma. Carboplatin is a highly effective chemotherapeutic agent against canine mesothelioma when used as a sole agent and in combination with gemcitabine

Design of Quality of Service Parameters for Voice over Long Term Evolution

VoLTE (Voice over LTE) is a solution to transfer voice packets over the LTE network, with low latency and high QoS (Quality of Service). As the efficient QoS assessment of VoLTE service is a crucial item for LTE networks operators and there are no studies were performed on commercial networks, and almost all previous studie

Embryotoxic and Teratogenic Effects of Norfloxacin in Pregnant Female Albino Rats

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 500 mg/kg·b·wt/day orally from 6th to 15th day of gestation. Groups B and C received 1000 and 2000 mg/kg·b·wt/day orally for the same period, respectively; Group D behaved as control and received 0.5 mL 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 fetuses; some visceral and skeletal defects in these fetuses were seen and these effects were dose dependant. Conclusively, norfloxacin caused some fetal defects and abnormalities, so it is advisable to avoid using this drug during pregnancy

Evaluation of the efficacy of mitochondrial fission inhibitor (Mdivi-1) using non-alcoholic steatohepatitis (NASH) liver organoids

Non-alcoholic steatohepatitis (NASH) is known to progress to cirrhosis and hepatocellular carcinoma in some patients. Although NASH is associated with abnormal mitochondrial function related to lipid metabolism, mechanisms for the development and effective treatments are still unclear. Therefore, new approaches to elucidate the pathophysiology are needed. In the previous study, we generated liver organoids from different stages of NASH model mice that could recapitulate the part of NASH pathology. In the present study, we investigated the relationship between mitochondrial function and NASH disease by comparing NASH liver organoids (NLO) and control liver organoids (CLO). Compared with CLO, mitochondrial and organoid morphology was abnormal in NLO, with increased expression of mitochondrial mitogen protein, DRP1, and mitochondria-derived reactive oxygen species (ROS) production. Treatment of NLO with a DPR1 inhibitor, Mdivi-1 resulted in the improvement of morphology and the decreased expression of fibrosis-related markers, Col1a1 and Acta2. In addition, treatment of NASH model mice with Mdivi-1 showed a decrease in fatty liver. Mdivi-1 treatment also prevented fibrosis and ROS production in the liver. These results indicate that NLO undergoes enhanced metabolism and abnormal mitochondrial morphology compared with CLO. It was also suggested that Mdivi-1 may be useful as a therapeutic agent to ameliorate NASH pathology

An adaptive sampling and weighted ensemble of surrogate models for high dimensional global optimization problems

The modern engineering design optimization relies heavily on high- fidelity computer.  Even though, the computing ability of computers have increased drastically, design optimization based on high-fidelity simulations is still time consuming and impractical.  Surrogate modeling is a technique to replace the high-fidelity simulations.  This paper presents a novel approach, named weighted ensemble of surrogates (WESO) for computationally intensive optimization problems, The focus is on multi-modal functions to identify its global optima with relatively few function evaluations.  WESO search mechanism falls in two steps, explore and fit. The “explore” step is based on exploring the whole design region by generating sample points (agents) using Latin hypercube sampling (LHS) technique to gain prior knowledge about the function of interest (learning phase).  The “fit” step is to train and fit a weighted ensemble of surrogate models over the promising region (training phase) to mimic the computationally intensive true function and replace it with a surrogate model (cheap function).  The surrogates are then utilized to select candidates’ decision variable points at which the true objective function and constraints’ functions to be evaluated.  Weights are then determined, assigned and an ensemble of surrogate gets constructed using the candidate sample points where optimization can be carried out.  WESO has been evaluated on classical benchmark functions embedded in larger dimensional spaces.  WESO was also tested on the aerodynamic shape optimization of turbo-machinery airfoils to demonstrate its ability in handling computationally intensive optimization problems.  The results showed to what extent combinations of models can perform better than single surrogate models and provide insights into the scalability and robustness of the approach. WESO can successfully identify near global solutions, faster than other classical global optimization algorithms

An adaptive sampling and weighted ensemble of surrogate models for high dimensional global optimization problems

The modern engineering design optimization relies heavily on high- fidelity computer.  Even though, the computing ability of computers have increased drastically, design optimization based on high-fidelity simulations is still time consuming and impractical.  Surrogate modeling is a technique to replace the high-fidelity simulations.  This paper presents a novel approach, named weighted ensemble of surrogates (WESO) for computationally intensive optimization problems, The focus is on multi-modal functions to identify its global optima with relatively few function evaluations.  WESO search mechanism falls in two steps, explore and fit. The “explore” step is based on exploring the whole design region by generating sample points (agents) using Latin hypercube sampling (LHS) technique to gain prior knowledge about the function of interest (learning phase).  The “fit” step is to train and fit a weighted ensemble of surrogate models over the promising region (training phase) to mimic the computationally intensive true function and replace it with a surrogate model (cheap function).  The surrogates are then utilized to select candidates’ decision variable points at which the true objective function and constraints’ functions to be evaluated.  Weights are then determined, assigned and an ensemble of surrogate gets constructed using the candidate sample points where optimization can be carried out.  WESO has been evaluated on classical benchmark functions embedded in larger dimensional spaces.  WESO was also tested on the aerodynamic shape optimization of turbo-machinery airfoils to demonstrate its ability in handling computationally intensive optimization problems.  The results showed to what extent combinations of models can perform better than single surrogate models and provide insights into the scalability and robustness of the approach. WESO can successfully identify near global solutions, faster than other classical global optimization algorithms

Comparative studies on the efficacy of lincomycin and bacitracin for the control of necrotic enteritis in broiler chickens

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 %, serum proteins, catalase, and superoxide dismutase. Additionally, a marked decrease in serum lipids was obtained. Furthermore, a significant increase in feed conversion rate, leukocytic count, phagocytic activity, phagocytic index, serum total globulin, γ globulin and malondialdehyde coupled with a marked increase in β and α globulins were determined. Medication of infected broilers with lincomycin and/or bacitracin improved clinical signs and reduced mortality rate to 8, 6 and 2%, respectively, as well as restored the performance and hematobiochemical alterations.Conclusions: a combination of lincomycin and bacitracin was of considerable value for the control of necrotic enteritis in broiler chickens

Pharmacokinetics and bioavailability of ceftiofur following intravenous and intramuscular administrations in broiler chickens

The study focussed on pharmacokinetics and bioavailability of ceftiofur (CFT) after receiving a single dose (2 mg/kg BW) through either intravenous (IV) or intramuscular (IM) injection. Eight broiler chickens, were used in a crossover design with a washout period of two weeks to analyze the behaviour of CFT. Ceftiofur concentrations in the plasma were determined by HPLC with UV detector. The pharmacokinetics of CFT was analyzed using non- compartmental analysis. Following IV injection, CFT elimination half-life (t1/2β) was 2.43 h, volume of distribution at steady state (Vdss) was 0.63 L/kg, and total body clearance (Cl) was 0.24 L/h/kg. Following a single intramuscular (IM) injection of CFT at the same dose, the drug was quickly absorbed into the bloodstream with an absorption half- life (t1/2ab) of 0.31 h. The maximum concentration of the drug in the plasma (Cmax) was 2.85 μg/mL and reached at a time (Tmax) of 0.57 h after injection and the bioavailability (F) of CFT was 96.25%. The results of the study revealed that CFT was absorbed rapidly and showed high bioavailability when administered by IM route. This suggests that CFT has a promising disposition in chickens, and its use could help determine the best dosage regimens for effective eradication of various infections in chickens