Pharmacokinetics of gatifloxacin in broiler chickens following intravenous and oral administration.

1. The pharmacokinetics of gatifloxacin were investigated following intravenous and oral administration of a single dose at a rate of 10 mg/kg body weight in broiler chicks. 2. Drug concentration in plasma was determined using High Performance Liquid Chromatography with ultraviolet detection on samples collected at frequent intervals after drug administration. 3. Following intravenous administration, the drug was rapidly distributed (t(1/2α): 0·33 ± 0·008 h) and eliminated (t(1/2ß): 3·62 ± 0·03 h; Cl(B): 0·48 ± 0·002 l/h/kg) from the body. 4. After oral administration, the drug was rapidly absorbed (C (max): 1·74 ± 0·024 µg/mL; T (max): 2 h) and slowly eliminated (t(1/2ß): 3·81 ± 0·07 h) from the body. The apparent volume of distribution (V(d(area))), total body clearance (Cl(B)) and mean residence time (MRT) were 3·61 ± 0·04 l/kg, 0·66 ± 0·01 l/h/kg and 7·16 ± 0·08 h, respectively. The oral bioavailability of gatifloxacin was 72·96 ± 1·10 %. 5. Oral administration of gatifloxacin at 10 mg/kg is likely to be highly efficacious against susceptible bacteria in broiler chickens.

Melanocortin peptide therapy for the treatment of arthritic pathologies.

Arthritic pathologies are a major cause of morbidity within the western world, with rheumatoid arthritis affecting approximately 1% of adults. This review highlights the therapeutic potential of naturally occurring hormones and their peptides, in both arthritic models of disease and patients. The arthritides represent a group of closely related pathologies in which cytokines, joint destruction, and leukocytes play a causal role. Here we discuss the role of naturally occurring pro-opiomelanocortin (POMC)-derived melanocortin peptides (e.g., alpha melanocyte stimulating hormone [alpha-MSH]) and synthetic derivatives in these diseases. Melanocortins exhibit their biological efficacy by modulating proinflammatory cytokines and subsequent leukocyte extravasation. Their biological effects are mediated via seven transmembrane G-protein-coupled receptors, of which five have been cloned, identified, and termed MC1 to MC5. Adrenocorticotrophic hormone represents the parent molecule of the melanocortins; the first 13 amino acids of which (termed alpha-MSH) have been shown to be the most pharmacologically active region of the parent hormone. The melanocortin peptides have been shown to display potent anti-inflammatory effects in both animal models of disease and patients. The potential anti-inflammatory role for endogenous peptides in arthritic pathologies is in its infancy. The ability to inhibit leukocyte migration, release of cytokines, and induction of anti-inflammatory proteins appears to play an important role in affording protection in arthritic injury, and thus may lead to potential therapeutic targets.

Kinetic studies of the interaction between isoniazid and reducing sugars.

The interaction between isoniazid and reducing sugars is acid-catalyzed and reversible. Kinetic studies of hydrazone formation from isoniazid and glucose, lactose, maltose, and galactose have been carried out in simulated gastric juice at 37 degrees C. The forward reaction was found to follow second-order kinetics, while the reverse reaction, the hydrolysis of the sugar isonicotinoyl hydrazone, is pseudo-first-order. The effects of the concentration of reactants, pH, and temperature on the rate have been studied, and the rate constants and the energy of activation were determined.

Multidimensional liquid chromatography of opioid peptides: fluorogenic labelling, retention prediction and separation optimization.

The ultra-trace analysis of opioid peptides in biological samples can be achieved by multidimensional liquid chromatography with pre-column fluorogenic derivatization with naphthalene-2,3-dicarboxaldehyde in the presence of cyanide ion. However, in order to take full advantage of the high sensitivity possible with detectors based on laser-induced fluorescence or chemiluminescence, each component of the analytical method must be carefully optimized. In this study, strategies are presented for the prediction of retention time and the optimization of separations of derivatized opioid peptides in multidimensional LC systems.

Puncture resistance and stiffness of nitrile and latex dental examination gloves.

OBJECTIVE: The aim of the current study was to assess the puncture resistance and stiffness of nitrile and latex dental examination gloves. METHODS: Puncture resistance was measured by employing an adapted version of ASTM F1342-91 using both a 316 stainless steel puncture probe (0.8 mm diameter) and a dental injection needle (0.45 mm diameter) interfaced to a tensile testing apparatus. Glove specimens (12 cm length, 1.5 cm breadth) were removed for modulus (M100) evaluation by assessing the force required to elongate the specimen to 100% of the original length. Glove samples were also aged to investigate whether puncture resistance and M100 values varied with aging at 70 degrees C for 7 days in an air-circulating oven. RESULTS: The nitrile glove types were assessed to have significantly higher puncture resistance compared with the latex glove type when the steel puncture probe was the pentrometer when using the one way analysis of variance (ANOVA) at the 95% significance level. Interestingly the puncture resistance for the latex glove type was significantly higher (P < 0.001) when a dental injection needle was used as the pentrometer compared with the nitrile glove types. The M100 values were significantly higher for the nitrile glove types for which the stiffness increased when the gloves were aged (P < 0.001). CONCLUSIONS: The higher stiffness values resulted in increased puncture resistance when the nitrile glove specimens were aged irrespective of the pentrometer type. However, the ability of latex to re-seal itself on puncture may be beneficial when considering the protection potential of each glove type against breaches in cross infection. For clinicians that have experienced an adverse reaction to natural latex gloves, the results of the current study indicate that nitrile gloves are available at reasonable cost and offer the clinician comparable resistance to puncture with latex gloves.

A pilot investigation of operator variability during intra-oral light curing.

OBJECTIVE: To test the hypothesis that operator experience influences the efficacy of light curing in a typical posterior intra-oral location. To investigate whether short cure cycles affect performance. DESIGN: A cross-sectional single-centre study designed to assess the efficacy of experienced and inexperienced operators when undertaking simulated intra-oral curing. SETTING: An in vitro laboratory based investigation conducted in a dental school during 2001. MATERIALS AND METHODS: A computer-based technique was used to monitor light intensity in a clinical simulation. Dentists and student operators were tested for their ability to cure a posterior restoration effectively. Relative light intensity was assessed against time for each operator and test run. RESULTS: Experienced (qualified) operators produced more effective and consistent cure results than less experienced undergraduate students. Operator performance was not affected by variations in irradiation time. CONCLUSIONS: This cross-sectional pilot investigation demonstrates that operator experience is a factor in successful clinical photo-curing of posterior restorations. Stable and accurate light guide positioning are required throughout the entire irradiation cycle to optimise intra-oral cure of light-activated restorations. Further investigations are planned to assess the potential of this novel method of assessment for use as a routine teaching aid in clinical practice.

A preliminary report on the incidence of pre-existing pinhole defects in nitrile dental gloves.

INTRODUCTION: Examination gloves manufactured from natural latex have been the predominant glove choice to date in dental practice. However, concerns over hypersensitivity have resulted in the use of alternatives such as nitrile gloves. The aim of the current study was to assess the incidence of pre-existing pinhole defects in nitrile examination gloves. METHODS: Air inflation, followed by water submersion, was used to assess the incidence of pre-existing pinhole defects in five nitrile and two latex glove types. The gloves were filled with a constant volume of air and submerged in 3 litres of water for 10 seconds while being observed for air bubbles which would indicate pinhole defects. The position and number of pinholes were noted for 100 gloves of each type investigated. RESULTS: The incidence of pre-existing pinholes for latex gloves was 0% for the non-sterile surgical latex glove type and 3% for the powdered latex examination glove type, with pinholes located on the thumb, middle finger and ring finger. Of the nitrile gloves evaluated, three types were assessed to have no pre-existing pinhole defects. One type had a 2% incidence of pre-existing pinhole defects--one pinhole located on the thumb region of the glove and one on the ring finger portion of the glove. The fifth nitrile glove type had one pre-existing pinhole defect located on the middle finger. SIGNIFICANCE: All glove types examined met the European Standard (EN 455-1) and there was no statistically significant difference between glove types. However, the nitrile gloves generally exhibited less pre-existing pinhole defects than the latex examination gloves.

Determination of orbifloxacin in sheep plasma by high performance liquid chromatography with ultraviolet detection after intravenous and intramuscular administration.

INTRODUCTION: Single-dose pharmacokinetics of orbifloxacin (2.5mg/kg body weight) were determined in clinically normal female Patanwadi sheep (n=6) following intravenous and intramuscular administration. METHODS: Orbifloxacin concentrations were determined by high performance liquid chromatography with ultraviolet detection. The concentration-time data were analyzed by non-compartmental kinetic method. RESULTS AND DISCUSSION: Following a single intravenous injection, an elimination half-life (t(1/2ß)) of 8.31±0.102h. Steady-state volume of distribution (Vd(ss)) and total body clearance (Cl(B)) were 3.09±0.282L/kg and 0.158±0.006L/kg/h, respectively. Following intramuscular administration, an elimination rate constant (ß), the area under the curve from zero to infinity (AUC(0-∞)) and the mean absorption time (MAT) were 0.015±0.001h(-1), 23.49±1.722µg·h/mL and 7.50±0.58h, respectively. The peak plasma concentration (C(max)) of 1.81±0.005µg/mL was achieved at 1.00±0.00h. The mean residence time (MRT) was 26.25±1.083h and the absolute bioavailability was 150.8±12.35%, respectively. Orbifloxacin could be useful for the treatment of bacterial infections in sheep that are sensitive to this drug.

Plasma disposition of conventional and long-acting moxifloxacin in sheep after intravenous administration.

This study describes disposition of long-acting moxifloxacin and conventional formulations of moxifloxacin in sheep after intravenous administration in five male sheep. Long acting moxifloxacin solution (10% moxifloxacin in solution with L-arginine, N-butyl alcohol, and benzyl alcohol) and conventional moxifloxacin (10%) were injected in jugular vein. Blood samples were collected from contralateral jugular vein in test tubes containing 30-50 IU heparin (anticoagulant) periodically from 0.083 to 72 h of drug administration. Drug concentrations in plasma were determined using High-Performance Liquid Chromatography (HPLC) with fluorescence detector. The mobile phase consisted of a mixture of buffer (10 gm of tetrabutyl ammonium hydrogen sulphate per liter-deionised water) and acetonitrile (80 : 20). The buffer was 0.067M of disodium hydrogen phosphate with pH of 7.5. The flow rate was 1 mL·min(-1) at ambient temperature. The effluent was monitored at 296 nm excitation and 504 nm emissions wavelength. HPLC with fluorescence detector method for plasma moxifloxacin assay was standardized with specific modification for plasma of sheep in the present study. After single-dose intravenous administration of long acting moxifloxacin the plasma concentration of 0.016 ± 0.001 µ g·mL(-1) was maintained for up to 72 h. Conventional formulation of moxifloxacin remained in body for up to 24 h of drug administration with the level of 0.015 ± 0.005 µ g·mL(-1).

Development and validation of an ultra performance liquid chromatography method for venlafaxine hydrochloride in bulk and capsule dosage form.

A simple, specific, accurate, and precise ultra performance liquid chromatographic method was developed and validated for the estimation of venlafaxine hydrochloride in tablet dosage forms. A acquity TM BEH column having C18, 100×2.1 mm i.d. in isocratic mode, with mobile phase containing dipotassium hydrogen phosphate: Acetonitrile (30:70 v/v; pH 7.00 with dilute o-phosphoric acid) was used. The flow rate was 0.75 ml/min and effluents were monitored at 227 nm. The retention time of venlafaxine hydrochloride was 0.548 min. The method was validated for specificity, linearity, accuracy, precision, limit of quantification, limit of detection, robustness and solution stability. Limit of detection and limit of quantification for estimation of venlafaxine hydrochloride were found to be 6.11 µg/ml and 20.33 µg/ml, respectively. Recoveries of venlafaxine hydrochloride in tablet formulations were found to be in the range of 99.3-99.5%. Proposed method was successfully applied for the quantitative determination of venlafaxine hydrochloride in tablet dosage forms.

Reversed-phase ion-pair liquid chromatography of the angiotensins.

The isocratic reversed-phase liquid chromatography of the angiotensins and a number of their synthetic analogues is described. Complete separation of 10 out of 12 peptides was achieved through a solvent optimization strategy with a total analysis time of about 20 min. The retention behavior of the angiotensins studied was described in terms of the hydrophobic contribution of their amino acid residues; there was good correlation between predicted and experimental retention for those peptides that were retained by a common mechanism. However, because ion-pair chromatography was required for good peak symmetry, retention was substantially modulated by the presence of acidic and basic residues. The limit of detection of these peptides was 3-5 pmol by UV absorbance at 214 nm. For those peptides containing a primary amino group the detection limit was improved by two orders of magnitude by fluorogenic derivatization with naphthalene-2,3-dicarboxaldehyde/cyanide to the corresponding N-substituted 1-cyanobenz[f]isoindole (CBI) derivatives. The contribution of the CBI ring system to retention was also investigated.

Radioiodination and biodistribution of analogs of a calichemicin constituent.

Analogs of the aromatic constituent of calichemicins were labeled with 131I by exchange reactions. Radiochemical yield for methyl-4-hydroxy-5-iodo-2,3-dimethoxy-6-methylbenzoate was approx. 90%. For methyl-4-benzyloxy-2-hydroxy-3-iodo-6-methylbenzoate the yield was about 30%. Biodistribution studies were carried out in mice following intravenous administration of tracer doses. Average brain uptake of the first compound at 3 min was 0.28%, and that of the second 1.96%. Tissue distribution of the two compounds elsewhere was similar in nature. High uptake was observed initially in the liver; this reduced with time, while radioactivity in the GI-tract increased. The benzylated compound appeared potentially useful for designing a brain imaging radiopharmaceutical.

Enhanced angiogenesis following allogeneic blood transfusion.

Blood transfusions are associated with recurrence of solid cancers. Angiogenesis is essential for cancer growth. Our aim was to determine for the first time in a prospective cohort study the effect of prestorage allogeneic leucodepleted SAGM (saline, adenine, glucose, mannitol) red cell transfusion on angiogenic factor levels and in vitro angiogenesis. Forty pretransfusion adult hospital inpatients were selected consecutively. Serum vascular endothelial growth factor (VEGF) and endostatin were measured in each patient before and after prestorage allogeneic leucodepleted SAGM red cell transfusion. All samples were exposed to an in vitro endothelial cell proliferation assay and 10 sample groups were also exposed to an in vitro whole angiogenesis assay. The median number of units transfused was 2 (minimum-maximum, 2-4). Twenty-nine (73%) patients had a rise in VEGF, with an overall increase of 118 pg/ml (quartiles -5, 306; P < 0.01). Twenty-eight (70%) patients had a decrease in endostatin, with an overall reduction of 1.2 ng/ml (quartiles 4.0, 0.0; P = 0.017). There was an overall 33% increase in endothelial cell proliferation (P < 0.01) and a 9.4% increase in in vitro whole assay angiogenesis (P < 0.01). Prestorage allogeneic leucodepleted SAGM red cell transfusions are associated with a favourable angiogenic factor imbalance and an elevation in in vitro angiogenesis.