An Herbal Nanohybrid Formula of Epigallocatechin Gallate-Chitosan-Alginate Efficiently Restrict the Sexual Dysfunction Adverse Effect of ß-Adrenergic Antagonist Drug: Propranolol.

The clinical studies proved the adverse effect of Propranolol on sexual function. Regarding this issue, the key research question of this study was, whether the designed herbal nanohybrid formula EGCG-chitosan-alginate has an efficacy versus Propranolol, or not? The formula was optimized according to the coacervation method. Its molecular structure and characteristics were confirmed. The entrapment efficiency was determined, and the stability, as well in vitro release study was conducted. The in vivo study was conducted for 65 days. To answer the raised question, tissue weights of the testis, epididymis seminal vesicles, and prostate were determined. Oxidative stress markers as MDA and GSH were measured in testis and epididymis, while testosterone in blood serum. The semen analysis was performed. DNA damage was detected according to the comet assay procedures. Conventional pathological examination was done in special concern to testis and epididymis. The characterization results reflected the good preparation of the formula with an amorphous structure in a range of 200 nm, high stability with ZP + 57.3 mV. The calculated EE was 84.10 ± 1.19% and the release percent was 72.11 ± 0.77% for 24 hrs. All the rats increased in the weight with variations among the groups in the tissue organs. The finding exposed a significant decrease in the average of MDA in the rats' testes with a significant increase in GSH while a non-significant difference in the epididymis, in both. The testosterone, the seminal parameters, and the DNA integrity significantly increased in the nano-formula compared to propranolol. Likewise, normal pathological findings of the nano-formula in the testis and Epididymis compared to abnormal of propranolol. In total, the current research confirmed that EGCG had no toxic effects and able to promote fertility. The most important finding was the administration of EGCG either in normal or nano-form prior to propranolol alleviated the effects of propranolol. These findings reflected the protection evident of EGCG versus propranolol.

Pharmacokinetics and tissue residue of enrofloxacin in healthy, Eimeria-infected broiler chickens and those pre-treated with amprolium and toltrazuril.

The pharmacokinetics of enrofloxacin was compared in healthy chickens, Eimeria infected chickens and in Eimeria infected chickens pre-treated with amprolium or toltrazuril following a single IV and oral administration at dose 10 mg/kg. The blood samples were taken after administration at different time intervals (5 min to 24 hours) to determine the pharmacokinetic parameters of enrofloxacin. The different concentrations of enrofloxacin were determined by using HPLC assay method. Serum concentrations versus time were analysed by a non-compartmental method. The results explored a significant decrease in serum concentrations of enrofloxacin at different time intervals and a significant change in pharmacokinetic profiles in Eimeria infected chickens compared with those values in healthy chickens whereas, amprolium improves these values. Toltrazuril leads to a significant decrease in enrofloxacin concentrations compared with infected non-treated chickens. Multiple-dose study revealed a longer withdrawal period of enrofloxacin in infected non-treated and infected chickens pre-treated with amprolium compared with the healthy group.

Bithionol residue analysis in animal-derived food products by an effective and rugged extraction method coupled with liquid chromatography-tandem mass spectrometry.

Herein, we developed a simple analytical procedure for the quantitation of bithionol residues in animal-derived food products such as porcine muscle, eggs, milk, eel, flatfish, and shrimp using a modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction method coupled with liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI+/MS-MS). Samples were extracted with 0.1% solution of formic acid in acetonitrile and the extract was purified using a C18 sorbent. Separation was performed on a Waters XBridge™ C18 reversed-phase analytical column using 0.1% solution of formic acid/acetonitrile as the mobile phase. Six-point matrix-matched calibration indicated good linearity, with the calculated coefficients of determination (R2) being≥0.9813. Intra- and inter-day recoveries (determined at spiking levels equivalent to 1×and 2×the limit of quantitation (0.25µg/kg)) ranged between 80.0 and 94.0%, with the corresponding relative standard deviations (RSDs) being≤8.2%. The developed experimental protocol was applied to different samples purchased from local markets in Seoul, which were tested negative for bithionol residues. In conclusion, the proposed method proved to be versatile and precise, being ideally suited for the routine detection of bithionol residues in animal-derived food products with various protein and fat contents.

Investigating the potential role of vitamin E in modulating the immunosuppressive effects of tylvalosin and florfenicol in broiler chickens.

Tylvalosin (TVS) is a third-generation macrolide drug used for prophylaxis and treatment of mycoplasma, however; it is supposed to possess an immunosuppressive effect. In the current study, the immunosuppressive effect of TVS and florfenicol (FFC) and the potential immunomodulatory role of Vit E were investigated. The experiment included one day old chick groups treated with either TVS, FFC, Vit E, TVS/Vit E, FFC/Vit E and control non-treated group. Chicks were vaccinated with inactivated H9N2 avian influenza (AI) vaccine and humoral antibody titers to viral antigen as well as innate immunity (serum lysozyme activity and nitric oxide levels) were evaluated. Total and differential leucocytic counts, serum liver enzymes level, blood leucocytic DNA damage and cellular area percentages within the lymphoid organs were also screened. Treatment with TVS and FFC significantly decreased immune response of chickens while treatment with Vit E improved the humoral immune response at 4 and 5weeks post-vaccination. Vit E also significantly increased the cellular immune response. The combination of Vit E with either TVS or FFC modulated their immunosuppressive effect and resulted in mild immunostimulatory effects. TVS alone induced a genotoxic effect on chickens' blood leucocytes and the genotoxicity was inhibited by combination of TVS with Vit E. Histopathology revealed that chickens treated with either TVS or FFC exhibited toxic effect on the lymphatic tissues.

Development and validation of a high-performance liquid chromatography-tandem mass spectrometric method for simultaneous determination of bupropion, quetiapine and escitalopram in human plasma.

In the present study, an effective high performance liquid chromatography-tandem mass spectrometric (HPLC/MS/MS) method was developed and validated to simultaneously determine bupropion (BUP), quetiapine (QUE) and escitalopram (ESC) in human plasma using carbidopa as the internal standard. Chromatographic separation was achieved on a Waters Sun Fire C18 column using reversed-phase chromatography. The MS/MS experiment was performed in positive ion multiple reaction monitoring mode to produce product ions of m/z 240.3 → 184.2 for BUP, 384.2 → 253.1 for QUE, 325.3 → 109.3 for ESC and 227.2 → 181.2 for the internal standard. The method showed good linearity (R(2) ≥ 0.997), precision (relative standard deviation ≤7.5%), satisfactory intra- and interday accuracy (88.4-113.0%) and acceptable extraction recovery (87.2-115.0%), matrix effect (84.5.5-108.7%) and stability (92.3-103.5%). The method was successfully applied to determine the concentrations of BUP, QUE and ESC in human plasma samples.

Pharmacokinetics of difloxacin in healthy and E. coli-infected broiler chickens.

1. The pharmacokinetics of difloxacin were investigated in healthy and E. coli-infected broiler chickens following intravenous and oral administration of a single dose of 10 mg/kg bodyweight. 2. After intravenous injection of difloxacin, the serum concentration-time curves were best described by a two-compartment open model. The distribution and elimination half-lives (t0.5α) and (t0.5el), respectively, were 0.10 ± 0.016 h and 3.7 ± 0.08 h in healthy chickens compared with 0.05 ± 0.005 h and 6.42 ± 0.71 h in E. coli-infected birds. The volumes of distribution Vdss were 3.14 ± 0.11 and 9.25 ± 0.43 l/kg, with total body clearance (Cltot) of 0.65 ± 0.018 and 1.14 ± 0.1 ml/kg/h, respectively. 3. Following oral administration, difloxacin was absorbed with t0.5(ab) of 0.57 ± 0.06 and 0.77 ± 0.04 h and was eliminated with t0.5(el) of 4.7 ± 0.34 and 3.42 ± 0.19, respectively, in normal and infected chickens. The peak serum concentrations were 1.34 ± 0.09 and 1.05 ± 0.06 µg/ml and attained a Tmax of 2.27 ± 0.07 and 2.43 ± 0.06 h, respectively. The systemic bioavailability of difloxacin following oral administration was 86.2% in healthy chickens and 90.6% in E. coli-infected birds. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of difloxacin against the field strain of E. coli O78 in vitro were 0.02 µg and 0.04 µg/ml, respectively. 4. These results show that administration of a therapeutic dose of difloxacin is effective in the treatment of E. coli infection in chickens. The serum concentration of the drug was much higher than the MIC of the E. coli O78 strain in both healthy and infected chickens.

Comparative bioequivalence study of three formulations of enrofloxacin in sheep.

A comparative pharmacokinetic study of three enrofloxacin injectable solutions was carried out in six healthy Barky rams after intramuscular injection according to a single dose, randomized, crossover experimental design. The three formulations were enrofloxacin 10% (Baytril(®)), enrofloxacin 10% plus bromhexine 1% (Mucotryl(®)) and enrofloxacin 10 % solution without bromhexine (Mucotryl without bromhexine). The three formulations were given a single intramuscular dose at a dose rate of 5 mg kg(-1) b.wt. The concentrations of the drug in the serum were measured using high-performance liquid chromatography (HPLC) with fluorescence detection. The results indicate that there were no significant differences between the distribution rate constant (k(ab)) and distribution half-life (t(1/2ab)), the maximum serum concentration (C(max)) and the time to peak concentration (T(max)) between Baytril and the other two formulations. There were significant differences between the elimination half life (t(1/2el)) and elimination rate constant (k(el)), for Baytril and enrofloxacin (the exact formulation of Mucotryl without bromhexine). Enrofloxacin was rapidly absorbed following IM administration of 5 mg kg(-1) b. wt. The peak serum concentrations (C(max)) were 2.83, 2.45 and 3.12 µg ml(-1) and were attained at (t(max)) 1.15, 1.41 and 1.26 hours when given Mucotryl, Baytril and enrofloxacin (the exact formulation of Mucotryl without bromhexine) to sheep, respectively. The injectable formulations investigated were bioequivalent after their intramuscular injection to sheep at recommended dose rate. As our results showed that, values of T(max), C(max) and AUC (Area under time curve concentration) determined for both Baytril, Mucotryl, and enrofloxacin (the exact formulation of Mucotryl without bromhexine ( reference ant test products) are within the acceptable range of 0.80-1.20, this means that the tested products product under investigation was bio-equivalent. These findings showed that the efficacy of the two test formulations was similar or possibly enhanced compared with Baytril based on the pharmacokinetic parameters obtained and due to concentration dependent activity of enrofloxacin.

Comparative pharmacokinetics of ivermectin alone and a novel formulation of ivermectin and rafoxanide in calves and sheep.

This study investigated the comparative serum disposition kinetics of ivermectin (IVM) after a single subcutaneous dose of 200 microg/kg body weight of IVM alone or in combination with an anthelmintic consisting of ivermectin and rafoxanide (200 microg/kg of IVM and 2.5 mg/kg rafoxanide) for use in calves and sheep. The IVM concentrations in serum samples were analyzed by high-performance liquid chromatography with fluorescence detection. In sheep serum, rafoxanide induced a rapid absorption of IVM when given in combined form manifested by a shorter absorption half-life time of IVM by 68.49% when given in combination as compared with IVM when given alone. In addition, there is an increase in the value of the area under the concentration curve (AUC) by 15.48% while the value of elimination rate constant was decreased by 38.2% and significantly increased the half-life time of elimination from 2.04 days for IVM alone to 3.3 days when given in combination with rafoxanide. In calves serum, the mean t1/2ab for IVM/rafoxanide was 0.131 days and for the control formulation 0.16 days, and t1/2el was 5.78 and 4.95, respectively. IVM Cmax for IVM/rafoxanide was 22.4 ng/ml and for the control formulation 19.1 ng/ml. T (max) values were 0.99 and 1.12 days, and the mean AUC values were 188.9 and 165.4 ng/ml/day. The difference in Cmax, AUC, Kab, K el, and t1/2el was significant. However, there was no statistical difference between the Tmax and t1/2ab. These findings revealed that the combination of rafoxanide with IVM in sheep and calves increased the absorption of IVM and delayed its elimination.

Anticoccidial efficacy of drinking water soluble diclazuril on experimental and field coccidiosis in broiler chickens.

Prophylactic and curative capacity of water soluble formulation of Diclazuril (Diclosol 1%) and feed additive form (Clinacox, 0.5%) were tested against Eimeria infection in broiler chickens. Such testing was performed both experimentally and in the field. Toltrazuril (Baycox, 2.5%) was used as reference control drug. Water soluble formulation of Diclazuril induced a marked inhibitory effect on the different stages of the parasite life cycle in experimentally infected treated birds especially when applied on the day when blood first appeared in the faeces [fifth day post-infection (d.p.i.)] as well as on the second day of blood dropping (6 d.p.i.). Both tested dosage levels of Diclazuril water soluble formulation in drinking water (5 and 10 ppm) showed the same effect in controlling coccidial infection and reducing the total oocyst numbers, lesion and faecal scores. Moreover, there was no significant difference in the efficacy of water soluble form of Diclazuril and the reference control drug (Toltrazuril, 25 ppm). In addition, testing the water soluble formulation (5 ppm) in naturally infected poultry farm (20,000 birds), showed the same anticoccidial effect observed when using Toltrazuril, as a treatment for coccidiosis. In conclusion, addition of Diclazuril at the dose of 5 ppm in the drinking water of naturally coccidia infected bird induced the same effect as 25 ppm of Toltrazuril as a treatment for coccidiosis in chickens.

Pharmacokinetics of difloxacin in goats.

The pharmacokinetic properties of difloxacin following intravenous (i.v.) and intramuscular (i.m.) administration in goats were investigated. Difloxacin was administered in a single dose of 5 mg/kg body weight for both routes and was assayed in biological fluids (serum and urine) to determine its concentrations, kinetic behaviour and systemic availability. Following a single i.v. injection, the serum difloxacin level was best approximated to follow a two-compartment open model using weighted non-linear regression analysis. The elimination half-life (t1/2 beta) was 6.3 +/- 0.11 h. The volume of distribution at steady-state (Vdss) was 1.1 +/- 0.012 L/kg and the total body clearance (Cltot) was 0.13 +/- 0.001 L/kg/h. Following a single i.m. administration, difloxacin was rapidly absorbed and the mean peak serum concentration (4.1 +/- 0.23 micrograms/ml) was achieved 1 h post administration. The extent of serum protein binding of difloxacin in goats was 13.79 +/- 1.02% and the systemic availability was 95.4 +/- 1.17%. Following i.m. injection of difloxacin at a dose rate of 5 mg/kg b.wt for 5 consecutive days, the drug could not be detected in serum and urine at 4th day from the last injection.

Disposition kinetics of danofloxacin and ciprofloxacin in broiler chickens.

Disposition kinetics of danofloxacin and ciprofloxacin were studied in broiler chickens following intravenous, intramuscular and oral administration in a single dose of 5 and 10 mg/kg-1 body weight respectively. In addition, tissue distribution and residual pattern of both drugs were determined. The maximum serum concentration (Cmax) after intramuscular and oral administration were 1.03 and 0.55 mu/ml for danofloxacin and 2.92 and 1.24 mu/ml for ciprofloxacin attained at 0.8 and 2.43 and 0.55 and 1.27 hours for danofloxacin and ciprofloxacin respectively. The volume of distribution and systemic bioavailability were higher for danofloxacin (Vdss 2.21 L/kg and F% 96.56 and 81.4%) as compared with ciprofloxacin (Vdss 1.41 L/kg and F% 75.5 and 29.4%). Data relating to intravenous injection for both drugs were analyzed using a two compartment open model curve fit. Danofloxacin and ciprofloxacin were not detected in the serum of broilers at the 5th and 3rd day respectively following the drugs withdrawal while were detected in liver, kidneys, spleen and lungs. Danofloxacin completely disappeared from all tissues at the 13th day after stopping of the drug medication but ciprofloxacin disappeared after 5 days only.

Synthesis and antihypertensive activity of certain Mannich Bases of 2-ethoxycarbonylindoles and 5H-pyridazin.

This manuscript reports the synthesis of two series of Mannich Bases 3-12 and 21-40 obtained respectively by the reaction of either 2-ethoxycarbonylindoles 1-2 or 5H-pyridazino [4,5b]inoles 17-20 as a substrate with formalin and the appropriate 2 degrees amines under the suitable Mannich conditions. Fourteen of the synthesized Mannich basese were screened as antihypetensive agents in normotensive anesthetized rats. The effect of compound 4 in normotensive anesthetized dogs was also studied.

Pharmacokinetics and intramuscular bioavailability of cefuroxime sodium in goats.

The pharmacokinetics of cefuroxime sodium, 20 and 40 mg kg(-1), were studied after i.v. and intramuscular injections in goats. Following single i.v. injections the serum concentration time curves of cefuroxime sodium were best fitted to a two-compartment open model. The drug was rapidly distributed with half-lives of distribution (t(1/2 alpha)) of 0.250 hours and 0.266 hours, and rapidly eliminated with half-lives of elimination (t(1/2 beta)) of 1.482 hours and 1.416 hours, respectively, following single i.v. injections of 20 and 40 mg kg(-1)body weight. After single intramuscular injections of cefuroxime sodium at the same doses, the mean absorption time (MAT) values were 1.379 and 1.716 hours and the peak serum concentration, C(max), was 12.965 and 38.50 microg ml(-1), attained after 0.515 and 0.608 hours (t(max)), respectively. The elimination half-lives (t(1/2el)) were 2.088 and 2.114 hours and the mean residence times (MRT) were 3.198 and 3.237 hours for 20 and 40 mg kg(-1)body weight, respectively. After both i.v. and intramuscular injections of cefuroxime sodium, the concentrations of cefuroxime in urine were much higher than that in serum. Urinary drug concentrations decreased gradually to reach their lowest levels at 24 and 48 hours post-injection, respectively. The systemic bioavailability of cefuroxime sodium in goats after intramuscular injections of 20 and 40 mg kg(-1)body weight was 88.4 per cent and 103.5 per cent, respectively. In vitro protein binding of cefuroxime sodium in goat's serum was low, ranging from 13.3 per cent to 21.6 per cent with an average of 17.0 per cent.

Pharmacokinetic interactions between flunixin and sulphadimidine in horses.

The pharmacokinetic aspects of sulphadimidine were studied in clinically healthy (control) and Flunixin-medicated horses after a single intravenous and oral administration of 100 mg/kg body weight. Plasma sulphadimidine concentration were determined by high-performance liquid chromatography (HPLC). Following the intravenous injection, all plasma sulphadimidine data were best approximated by a two-compartment open model using sequential, weight non-linear regression. Flunixin induced a 67% increase in the rate of sulphadimidine return to the central compartment from peripheral tissues (K21) and there were a trend to a 30% increase in K12. The sulphadimidine elimination half-life was decreased 21%, the Vdss was reduced by 18% and MRT was decreased by 20%. Following the oral administration, sulphadimidine was rapidly absorbed in control and Flunixin-medicated horses with absorption half-lives (t1/2 ab) of 0.5 and 0.43 hours respectively. The peak plasma concentration (Cmax) were 93.7 and 109 micrograms/ml attained at (tmax) 2.36 and 1.9 hours respectively. The elimination half-life after oral administration (t1/2 ab) was shorter in flunixin pre-medicated horses than in control ones. The systemic bioavalability percentages (F%) of sulphadimidine after oral administration of 100 mg/kg body weight was 79.3 and 71.2% in control and flunixin medicated horses, respectively. Therefore care should be exercised in the use of sulphadimidine in equine patients concurrently treated with flunixin.

Comparative pharmacokinetics of diminazene in lactating goats and sheep.

The pharmacokinetic aspects of diminazene aceturate were studied in lactating goats and sheep after single intravenous and intramuscular administrations of 3.5 mg/kg b.wt. Plasma and milk concentrations were determined by use of reversed phase high-performance liquid chromatography (HPLC) after ion-pair extraction. Following intravenous injection, the disposition of diminazene in goats and sheep conformed to a two-compartment model with rapid distribution and slower elimination phases. Values of (t1/2 beta) were obtained indicating a slower final disappearance of the drug from plasma of sheep (21.17 h) than in goats (16.39 h). Diminazene concentrations were maintained for more than 4 days in the plasma of goats and sheep. In both species of animals, diminazene was rapidly absorbed following intramuscular administration of 3.5 mg/kg b.wt. The peak plasma concentrations (Cmax) were 7.00 and 8.11 micrograms/ml and were attained at (Tmax) 0.92 and 1.12 hours in goats and sheep, respectively. The elimination half-life (t1/2el) of diminazene after intramuscular administration was shorter in goats (16.54 h) than in sheep (18.80 h). Systemic bioavailabilities (F%) of diminazene after intramuscular administration were 94.94% and 82.64% in goats and sheep, respectively. Diminazene could be detected in milk of goats and sheep within 10 min post-injection. Milk concentrations of the drug were lower in goats than in sheep and were detected for 5 and 6 days following both routes of administration, respectively.

Pharmacokinetics of florfenicol in normal and Pasteurella-infected Muscovy ducks.

1. Disposition kinetics of florfenicol were studied in Pasteurella-free (control) and Pasturella-infected Muscovy ducks following intravenous and/or intramuscular injection in a single dose of 30 mg/kg body weight. In addition, the tissue distribution and residual pattern of the drug were determined in diseased ducks. 2. The maximum serum concentration of florfenicol in control healthy and infected ducks was reached 1 hour after intramuscular injection but the peak concentration in control ducks was higher than in infected birds. 3. The volume of distribution, total body clearance and systemic bioavailability were higher in infected ducks than in control birds 5.15 l/kg, 10.24 ml/kg/min and 73.03% respectively. Data relating to intravenous injection were analysed using a 2 compartment open model curve fit. 4. Florfenicol was not detected in the serum of infected ducks on the 7th day following intramuscular administration of 30 mg/kg body weight twice daily for 5 successive days but was detected in kidney, bile and liver.

Disposition kinetics of ciprofloxacin in lactating goats.

The pharmacokinetics of ciprofloxacin following intravenous and intramuscular administrations in lactating goats were investigated. Ciprofloxacin was administered as a single dose of 5 mg kg-1 body weight for both routes and was assayed in biological fluids, (serum, milk and urine) to determine its concentrations, kinetic behaviour, and systemic availability. Following a single i.v. injection, the serum concentration-time curve was best described by a two-compartment open model. The elimination half-life (t0.5 beta) was 2.78 +/- 0.08 hours. The extent of serum protein binding of ciprofloxacin in goats was 14.2 +/- 1.4%. Volume of distribution at steady-state was 2.14 +/- 0.07 L/kg. Total body clearance of ciprofloxacin in goats was 14.7 +/- 0.43 ml/min/kg. Following a single intramuscular administration, ciprofloxacin was rapidly absorbed and the mean peak serum concentration (1.92 +/- 0.05 micrograms ml-1) was achieved 1 hour post administration. The systemic availability of ciprofloxacin after intramuscular administration was 95.9 +/- 6.4%. The drug was detected in therapeutic concentrations for 10 hours in serum and milk and for 24 hours in urine. Following intramuscular injection at 5 mg kg-1 body weight for 5 consecutive days, ciprofloxacin showed a cumulative behaviour in serum, milk and urine of goats.

Extracts and fractions of Thymus capitatus exhibit antimicrobial activities.

Preliminary phytochemical screening of the plant Thymus capitatus exhibited the presence of saponins, resins, flavonoids, essential and fixed oils. Aqueous and ethanolic extracts (10-200 mg/ml) as well as saponin, resin and essential oil of the plant (10-5000 micrograms/ml inhibited the growth of several bacteria and fungi.

Influence of E. coli infection on the disposition kinetic of nalidixic acid in broiler chickens.

The pharmacokinetic data of nalidixic acid were investigated in normal and E. coli infected chickens. The highest serum concentration were reached after 2 hours with t0.5 (ab) of (1.706 +/- 0.1 min in normal and 2.030 +/- 0.11 min in diseased) and (1.72 +/- 0.11 min in normal and 1.416 +/- 0.044 in diseased chickens) following oral and intramuscular administration, respectively. The elimination half-life t0.5 (beta) were (2.514 in normal and 2.35 hr in diseased) and (2.567 hr in normal and 2.672 hr in diseased) respectively. Following intravenous injection the kinetic of nalidixic acid followed two compartments open model with t0.5 of (6.27 and 9.15 hr), Vd (0.45 and 0.79 L/kg), Cltot (8.86 and 13.32 ml/kg/min) in normal and E. coli infected chickens, respectively. Administration of nalidixic acid twice daily for 5 successive days in a dose level of 25 mg/kg b. wt. by oral and intramuscular routes showed a cumulative behaviour.