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C.V

Curriculum Vitae

 PERSONAL DETAILS

    Famiy name                   Ali

    Fore name                     Fatma 

    Full name                          Fatma Ibrahim Abo El – Ela Ali

     Date of Birth                         8/8/1987

     Country of birth                    Egypt

    Nationality                             Egyptian

    Home Address                        13 El Court st,Abo korkas , El Minya, Egypt.

    Correspondence                     Pharmacology Dep., faculty of veterinary medicine

    Adress                                    Beni- Suef,Egypt

    Social status                           Married

Mobile                                    +2 01152460404

E mail                                   fa.pharma@yahoo.com

Language skills                     Good command in English ( ELITS 5.5)

 ACDADEMIC DETAILS - HIGHER EDUCATION

 

 Instituation 

   

Master Title

Pharmacokinetics and Efficacy of Difloxacin In Broiler Chi

Master Abstract

Summary ********* The present work was carried out to reveales some pharmacokinetic aspects of difloxacin in both healthy and infected chickens.The bioavailability of difloxacin following oral adminstration were estimated in both healthy and infected chcikens. The protien binding percent of the drug to serum was also estimated. Determination of MIC and MBC of the drug also estimated. The present study was carried out on 18 chickens . These birds were obtained from poultry farm in Fayoum Governorate with an avearage body weight from 1.800 to 2. 00 kg and proved to be clinically healthy. In the first experiment six clinically healthy chickens were given difloxacin hydrochloride 10mg/kg b.wt. as a single intravenious dose (through wing vein) and single oral dose (intra-crop route) with two weeks washout period between each route. Blood samples were collected 5, 10, 15 and 30 min. 1, 2, 4, 6, 8, 12 and 24 hours post injection. The concentration of the drug in serum sample was determined using the microbiological assay method. In the second experiment, 12 chickens divided into two groups (6 chickens in each). Each chicke infected with avian pathogenic E.coli O78.thats increasing its virulence through E.coli injection into one day old chicks then heart isolated on macConkey agar media as a specific media for E.coli. The minimum inhibitory concentration and minimum bactericidal concentration of the drug to Escherchia.coli (strain O78) was also investigated. 1- Intravenous injection of difloxacin in healthy chickens : After intravenous injection of difloxacin in a dose of 10 mg /kg b.wt. , the drug was showed a high serum level (8.02 ug / ml) 5 min post injection, then the concentration decreased gradually till reached its minimum level (0.15 ug/ ml) at 24 h post –injection. The present data revealed that the serum concentration time curves of difloxacin were best described by a two compartment –open model. The drug was rapidly distributed with a distribution half-life (t 0.5 a) of 5.84 h and apparent volume of distribution calculated by extrapolation Vd(B), area Vd(area), pseudo equilibrium Vc and steady state Vd(ss) methods were 3.89, 3.95, 0.81 and 3.14 l/kg respectively. The drug was distributed in the central compartment with a volume of distribution (Vc) 0.81 l/kg., indicating that the drug is highly distributed in extra vascular tissues. The drug was rapidly eliminated with a half-life of elimination (t0.5ß) of 3.7 and the body clearance of difloxacin (ClB) was 0.65 ml/kg/h. The mean residence time (MRT) was 4.73 h. 2- Oral administration of difloxacin in healthy chickens : Following oral administration of difloxacin in a single dose of 10 mg/kg b.wt., the drug was detected in serum 0.25 h post injection (0.06 ug/ ml) and it continued to increase gradually thereafter and was reached its maximum level 1.46 ug/ml at 2 h post injection, then started to decrease gradually till reached its lowest concentration 0.09 ug/ ml at 24 hours. It was rapidly absorbed with a half-life of absorption (t0.5ab) of 0.57 h., while its elimination half-life (t0.5el) was 4.7 h .The systemic bioavailability of difloxacin following oral administration was 86.24 %. This indicated good absorption of the drug from this site of injection. The in vitro protein binding percent to serum was 3.99 %. 3- Intravenous injection of difloxacin in infected chickens: After intravenous injection of difloxacin in a dose of 10 m g/kg b.wt. in infected chickens the drug was showed a high serum level (4.67 ug/ml) 5 min. post injection, then the concentration decreased gradually till reached its minimum level (0.07 ug/ ml) at 24 h post –injection. The present data revealed that the serum concentration time curves of difloxacin were best described by a two compartment –open model. The drug was rapidly distributed with a distribution half-life (t0.5 a) of 3.3 h and apparent volume of distribution calculated by extrapolation Vd(B), area Vd(area), pseudo equilibrium Vc and steady state Vd(ss) methods were 11.96, 11.03, 0.9 and 9.25 L/kg respectively. The drug was distributed in the central compartment with a volume of distribution (Vc) 0.9 L/kg., indicating that the drug is highly distributed in extra vascular tissues. The drug was rapidly eliminated with a half-life of elimination (t0.5ß) of 6.42 and the body clearance of difloxacin (ClB) was 1.14 ml/kg/h. The mean residence time (MRT) was 8.34 h. 4- Oral administration of difloxacin in infected chickens: Following oral administration of difloxacin in a single dose of 10 mg /kg b.wt., to the infected chickens the drug was detected in serum 0.25 h post injection (0.028 ug ml-1) and it continued to increase gradually thereafter and was reached its maximum level 1.19 ug / ml at 2 h post injection, then started to decrease gradually till reached its lowest concentration 0.047 ug/ml at 24 hours. It was rapidly absorbed with a half-life of absorption (t0.5ab) of 0.77 h., while its elimination half-life (t0.5el) was 3.42 h. The systemic bioavailability of difloxacin following oral administration was 90.6 %. 6- In –vitro activity of difloxacin against E.coli : Escherchia.coli strain O78 was sensitive to difloxacin. The minimum inhibitory concentrations of difloxacin that prevent the growth of the microorganism, was 0.02 ug/ml while the minimum bactericidal concentration of the drug that kill them was 0.04 ug/ml. Difloxacin drug is therapeutically effective in treatment of E.coli infection along all the day (24h).

PHD Title

Immunopharmacological effects of some drugs

PHD Abstract

Summary The present study was conducted to investigate the immuno-pharmacological effects of tylvalosin, florfenicol and vit E alone or in combination on the cellular and humoral immune in New Castle and Avian influenza vaccinated broiler chickens in addition to, the pharmacokinetics of the mentioned drugs and their combination were also evaluated and to connect between the drug kinetics (serum concentration) and their effects on the immune system in relation to their their blood concentration besides vit E effects on these drugs. Moreover, the genotoxic effect on leucocytes and the histopathological changes in lymphoid organs were also studies as well as image analysis of the microscopic histopathology were also determined as a representative to the cellular percentage affects by each treatment(Area percentage). a-Immunological study: In this study, a total of a total of three hundred (300) one day old broiler chicks were housed in disinfected deep letter system in a well-ventilated and vaccinated with different vaccines (New Castle, Avian Influenza, Gumboro (IBD) and IB (infectious bronchitis) then were divided into 6 groups each divides into 2 repeats as each group (30 bird) as the following: -The First group (G1) (2 repeats) was vaccinated and treated orally in the calculated water in (24h) with tylvalosin (Aivlosin) 625 mg/gm at s dose of 25mg/kg b.wt. for three (3) successive days. -The Second group (2 repeats) was vaccinated and treated orally in the calculated water in (24h) with Florfenicol (pure powder) 98% at a dose of 30 mg/kg b.wt, for five (5) successive days. -The third group (2 repeats) was vaccinated and treated orally in the calculated water in (24h) with vit E (pure powder) 50% at a dose of 2 mg/kg b.wt. for three (3) successive days. -The Fourth group (2 repeats) was vaccinated and treated with tylvalosin-vit E combination drugs orally in the calculated amount of water in (8h) for the (tylvalosin) at a dose of 25 mg/ kg b.wt. and in (16h) for vit E (2 mg/ kg b.wt) for three 3 successive days . -The Fifth group (2 repeats) was vaccinated and treated with florfenicol-vit E combination drugs orally in the calculated amount of water in (8h) for the (florfenicol) at a dose of (30 mg/ kg b.wt.) and in (16h) for Vit E (2 mg/ kg b.wt) for five (5) successive days. -The sixth group (2 repeats) was vaccinated non treated as left as control negative. Two blood samples were collected from the wing vein and from the heart of each chickens or by slaughtering at the zero day of the experiment and subsequently weekly after vaccination at 14th, 18th, 21th , 28th , 35th and 42th day of age for humoral immunity evaluation through HI technique a) sample 1: Whole blood (2-3 ml) was collected from the wing vein in a sterile Wasserman tube containing EDTA (0.5 mg/ml of blood) to be used for determination of total and differential leucocytic counts, and tubes with Heparin anticoagulant for assessment of genotoxicity by the comet assay. b) sample 2: In a sterile Wasserman tube, 3-5 ml of blood was collected from the wing vein without an anticoagulant .The samples were allowed to coagulate, and then the serum was separated by centrifugation at 3000 r.p.m. for 10 minutes and stored at -20 Co in sterile Eppendorf tubes until used for estimation of the humoral immune response, and for determination of serum nitric oxide and Lysozyme activity. At the end of the experiment at about 45th day of age 4 chickens of each group were slaughtered and the lymphoid organs (spleen and bursa) were collected to be used for studying the histopathological changes. b- pharmacological study: The pharmacokinetic aspects of tylvalosin, florfenicol and their combination with vit E in healthy brolier chickens.the pharmacokinetics parameters were determined after single and continuous adminstration of the different drugs and their combination.The protien binding percent of the drugs to serum was also estimated. The total number of chickens (24) were divided into four (4) groups each group six (6) chickens, The all groups received (4) different drugs to each group and they were given the different drugs after single oral dose (intra-crop route) and continous adminstration orally to the same groups. The chickens were calssified according to the treatment into four different groups as the follow: Group (1): was adminstered orally with tylvalosin (Aivlosin) 625mg/gm at s dose of 25mg/ kg b.wt. Group (2) : was administered orally with florfenicol (pure powder) 98% at a dose of 30 mg/kg b.wt, Group (3): was administered orally with tylvalosin-vit E combination orally (tylvalosin) at a dose of 25 mg/ kg b.wt. and vit E (2 mg/ kg b.wt) for three successive days. Group (4): was administered orally with florfenicol-vit E combination orally (florfenicol) at a dose of 30 mg/ kg b.wt. and vit E (2 mg/ kg b.wt) for five 5 successive days as a single dose and for another five days in the same chickens for continuous dosing . - Vit E administered first (before the second drug) to the chickens in the drug combination groups . Sampling: Blood samples (1ml each) were collected from each chicken in a sterile Wasserman tube without anticoagulant from the wing vein, Jugular vein, wing vein puncture and heart puncture. just after 5,10,15,30 minutes,1,2,4,6,8,12 , 24,48 hours post single drug administration and for another72 hour for continuous adminstration in tylvalosin and tylvalosin-vit E while till 96 hour in florfenicol and florfenicol and florfenicol-vit E groups single dosing and for another 96 hour in the same groups for continuous adminstration I-Effect on the cellular immunity: 1- Effect on total leucocytic count: Both tylvalosin and florfenicol had been evoked a significant decrease in the total leucocytic count at 21th day and 35th day post the last live vaccination administered to the chickens against New Castle disease virus while, chickens administered vit E drug showed a significant increase in the total leucocytic count along the 2 weeks. In tylvalosin-vit E and florfenicol-vit E drug combination groups showed a significant increase in the total leucocytic count at 21th and 35th day of age . 2- Effect on differential leucocytic count: There were significant decrease in both lymphocytes and neutrophilss percentage at 21th day and 35th day post drug administration in tylvalosin and florfenicol administered groups, On the other hand vit E, tylvalosin-vit E and florfenicol-vit E treated chickens showed a significant increase but no significant effects were determined in the other cell types. 3- Effect on serum nitric oxide level: Nitric oxide level was significantly decreased in the treated groups with tylvalosin and florfenicol at 21th day and 35th day while,vit E treated chickens showed the most significant increase in nitric oxide level compared with the other groups . Moreover, groups of chickens treated with tylvalosin-vit E and florfenicol-vit E groups showed no significant increase in nitric oxide level at 21th day and 35th day of the experiment. 4- Effect on serum Lysozyme activity: Administration of tylvalosin and vit E to vaccinated broiler chickens showed a significant increase in the serum lysozyme activity at 21th day and 35th day of the experiment, On the other hand administration of florfenicol elicited a significant decrease in the serum lysozyme level. Mean while, tylvalosin-vit E (revealed the highest serum lysozyme in between the all groups) and florfenicol-vit E administered groups showed a significant increase in the serum lysozyme activity. II – Effect of tylvalosin, florfenicol, vit E and their combination on humoral immunity: 1- Effect on haemagglutination inhibition (HI) antibody titers: Both tylvalosin and florfenicol administered groups showed decrease in the antibody titer in vaccinated chickens at 18th day, 21th day, 28th day 35th day and 42th day of age, On the other hand there was a significant increase in the antibody titers in vit E administered group. Meanwhile, in tylvalosin-vit E group vit E make slight modulation to the effect of tylvalosin on antibody titer as it causes increase in the antibody titer well observed at 21th day and 28th day .Group of chickens administered florfenicol-vit E also caused decrease in the antibody titer as vit E not modulate the decrease of florfenicol in the antibody titer. 2- Effect on serum total protein, albumin and globulin levels: Administration of tylvalosin, florfenicol, or tylvalosin-vit E, florfenicol-vit E combination evoked non-significant changes in total serum protein level but serum albumin level was significantly increased in groups of chickens administered tylvalosin and florfenicol , On the other hand group of chickens administered vit E showed a significant decrease in the serum albumin level but tylvalosin and florfenicol treated chickens showed decrease in the serum globulin , On the other hand the other vaccinated treated groups as vit E, tylvalosin-vit E and florfenicol-vit E revealed a higher significant increase in serum globulin III- Effect on tail moment (Genotoxicity using the comet assay): A remarkable significant increase in tail moment was recorded in tylvalosin and tylvalosin-vit E administered group, On the other hand no significant difference were recorded for the other treatments on the DNA of the leucocytes IV-Histopathological findings in lymphoid organs: a-Microscopic (morphological analysis): In tylvalosin and florfenicol treated chickens showed severe lymphoid depletion in the lymphoid follicles of bursa and spleen with severe shrinkage of both covering epithelium and follie as well as highly increasing in the inter-follicular spaces On the other hand, vit E treated chickens showed hyperplasia in the lymphoid follicles, highly aggregation of lymphocytes in the germinal center and the covering epithelium appear tall and ciliated. Meanwhile, tylvalosin-vit E and florfenicol-vit E treated chickens have been showed modulatory effects on the depleted lymphoid follicles b- Image Analysis (Area of cellular percentage (%) by numbers: Image analysis had been done to the histopathological (morphological analysis) of the immune organs through calculation the cellular percentages of each treatment in this study and expressed by the area percentages of the cellular mass in each treatment, The analysis of the microscopic morphology had been revealed significance effect between the different groups specially between tylvalosin and the control groups -Pharmacokinetic aspects of a single and continuous administration of tylvalosin , florfenicol and their combination: 1- Single oral administration of tylvalosin in control healthy broiler chickens : The drug was firstly detected (0.05) after 15 minutes and the maximum serum level (2.25 ug/ml) was reached at 2 hour after the drug administration. The peak concentration (Cmax) was 2.11ug/ml and the calculated value of tmax was 2.06hour. The drug was absorbed from healthy broilers gut with absorption half-life (t0.5ab) of 0.94 hour and eliminated with a mean half-life (t0.5 el) of 1.61 hour. 2- Repeated oral administration of tylvalosin in control healthy broiler chickens: The drug was firstly detected (0.07ug/ml) after 5 minutes and the maximum serum level (5.01ug/ml) was reached at 2 hour after the drug administration. The peak concentration (Cmax) was 4.1ug/ml and the calculated value of tmax was 2.19 hour. The drug was absorbed from healthy broilers gut with absorption half-life (t0.5ab) of 1.39hour and eliminated with a mean half life (t0.5 el) of 2.78hour. 3-Single oral administration of tylvalosin-vit E in control healthy broiler chickens: The drug was firstly detected (0.23ug/ml) after 15 minutes and the maximum serum level (3.77ug/ml) was reached at 2 hour after the drug administration. The peak concentration (Cmax) was 3.27ug/ml and the calculated value of tmax was 2.18hour The drug was absorbed from healthy broilers gut with absorption half-life (t0.5ab) of 0.88 hour and eliminated with a mean half life (t0.5 el) of 2.42hour. 4-Repeated oral administration of tylvalosin-vitE in control healthy broiler chickens: The drug was firstly detected (0.15ug/ml) after 5 minutes and the maximum serum level (5.9ug/ml) was reached at 2 hour after the drug administration. The peak concentration (Cmax) was 5.67ug/ml and the calculated value of tmax was 2.25 hour The drug was absorbed from healthy broilers gut with absorption half-life (t0.5ab) of 0.86 hour and eliminated with a mean half life (t0.5 el) of 3.05hour. 5-Single oral administration of florfenicol in control healthy broiler chickens : The drug was firstly detected (0.73 ug/ml) after 10 minutes and the maximum serum level (6.46 ug/ml) was reached at 1 hour after the drug administration. The peak concentration (Cmax) was 5.9ug/ml and the calculated value of tmax was 1.40 hour The drug was absorbed from healthy broilers gut with absorption half-life (t0.5ab) of 0.51 hour and eliminated with a mean half life (t0.5 el) of 2.72 hour. 6- Multiple oral administration of florfenicol in control healthy broiler chickens : The drug was firstly detected (0.62g/ml) after 5 minutes and the maximum serum level (7.47ug/ml) was reached at 2 hour after the drug administration. The peak concentration (Cmax) was 7.4 ug/ml and the calculated value of tmax was 2.3hour The drug was absorbed from healthy broilers gut with absorption half-life (t0.5ab) of 0.82 hour and eliminated with a mean half life (t0.5 el) of 3.77hour. 7- Single oral administration of florfenicol-vit E combination in control healthy broiler chickens: The drug was firstly detected (0.61ug/ml) after 5 minutes and the maximum serum level (7.55ug /ml) was reached at 2 hour after the drug administration. The peak concentration (Cmax) was 7.48ug/ml and the calculated value of tmax was 2.42 hour. The drug was absorbed from healthy broilers gut with absorption half-life (t0.5ab) of 0.71 hour and eliminated with a mean half-life (t0.5 el) of 4.34 hour. 8- Multiple oral administration of florfenicol-vitE combination in control healthy broiler chickens : The drug was firstly detected (0.74 ug/ml) after 5 minutes and the maximum serum level (8.38 ug/ml) was reached at 2 h after the drug administration. The peak concentration (Cmax) was 8.07 ug/ml and the calculated value of tmax was 2.5 hour The drug was absorbed from healthy broilers gut with absorption half-life (t0.5ab) of 0.81 h and eliminated with a mean half-life (t0.5 el) of 4.3 hour. In conclusion; both tylvalosin and florfenicol drugs evoke immunoinhibitory effects whereas, vit E showed immunostimulatory response. In addition; vit E not completely modulate the immunosuppressive effects of the mentioned drugs when combined with them and this may attributed to the lower dose of vit E used in this study or due to vit E increased the serum concentrations of the drugs when used in combination in the pharmacokinetic studies so increasing their immunosuppressive effects. In the pharmacokinetic studies both tylvalosin and florfenicol had serum cumulative effects leading to an increase in the time of their elimination besides their combination with vit E also increasing their serum concentration and prolongation the duration of their action for more 12 and 24 h after single and multiple administration.