Influence of administration route on the biotransformation of amoxicillin in the pig

A comparison was made in the plasma concentration of the major metabolites of amoxicillin (AMO), i.e. amoxicilloic acid (AMA) and amoxicillin diketopiperazine-2',5'-dione (DIKETO) in portal and jugular venous plasma after oral (p.o.) and intravenous (i.v.) AMO administration to pigs, in order to study a possible presystemic degradation of AMO in the gastro-intestinal tract and liver. Almost identical plasma concentration-time curves were obtained for AMO and its metabolites in portal and jugular venous plasma, both after p.o. and i.v. AMO administration. Almost immediately after i.v. AMO administration, high AMA and DIKETO concentrations were measured in plasma, while after p.o. dosing, the metabolites appeared in plasma after almost complete absorption of AMO. No significant differences in pharmacokinetic parameters of AMO, AMA and DIKETO, derived from the concentration-time profiles in portal and jugular venous plasma were calculated, both after i.v. and p.o. AMO administration ( P  > 0.05). After p.o. administration, the half-life of elimination ( t _1/2(el)) for AMA is at least two or three times the t _1/2(el) of AMO (0.75 h for AMO vs. 2.69 h for AMA), indicating the slower clearance of the metabolite. It could be hypothesized that AMA is only eliminated by glomerular filtration, as its open β-lactam structure might not be recognized by the transport carrier in the proximal tubule of the kidney. The results of the study indicate that AMO is not substantially metabolized presystemically in the gut and liver. Therefore, it may be assumed that the kidney may be the major organ for AMO biotransformation. Future in vivo and in vitro experiments should be performed to state this hypothesis.     

Transsplenic portal catheterization combined with a jugular double-lumen catheter for pharmacokinetic and presystemic metabolization studies in pigs

The reliability of a silicone double-lumen catheter implanted into the external jugular vein and tunnelled towards the neck region was investigated in eight pigs. Surgery was uneventful without interference with the normal homoeostasis during 8 days. After injection of amoxicillin/clavulanic acid through the distal port of the catheter, analysis of drug components in the simultaneous blood samples obtained by the proximal port and a Venoject^® system were comparable in one pig. Histological control of the catheterized jugular veins pointed to an acceptable tissue reaction while bacteriological examination of the tip of the catheters was negative in only three animals. A moulding of the intestinal veins was made in a pig cadaver to determine the optimal length of insertion of a silicone portal catheter from the splenic vein towards the portal vein. Surgery was straightforward in four pigs whereby the catheter was exteriorized towards the back region. No complications were encountered during and after surgery for 9 days. The technique of a double-lumen catheter placed into the jugular vein and a transsplenic portal catheter is a useful tool for the study of the pharmacokinetics and also the first-pass effect of drugs in experimental pigs.     

Effects of fasting on circulating IGF-binding proteins, glucose, and cortisol in channel catfish (Ictalurus punctatus)

The effects of fasting on IGF-binding proteins (IGFBPs), glucose, and cortisol in channel catfish were examined. Fed fish (controls) were compared to 14-, 30-, and 45-day fasted fish and 45-day fasted fish refed for 15 additional days. Body length and weight changes, condition factor (CF), hepatosomatic index (HSI), and plasma glucose and cortisol were assessed to determine growth and metabolic status. Body length and growth rates were inhibited (P<0.05) after 14, 30, and 45 days of fasting. The 14-, 30-, and 45-day fasted fish exhibited hypoglycemia and reduced CF and HSI. Cortisol levels were increased (22.8 +/- 15.2 ng/ml versus 4.7 +/- 3.9 ng/ml) in 30-day fasted fish compared to fed controls (P<0.05). Associated with the increase in cortisol in fasted fish was a concomitant increase in plasma levels of a 20-kDa IGFBP through day 45. A 35- and a 45-kDa IGFBP were also identified but were similar between fed and unfed fish throughout the experiment. At the end of 15 days of refeeding, 20-kDa IGFBP, glucose, and cortisol levels were similar to fed controls. Refeeding also caused an increase in growth rates. These results suggest the existence of a catfish counter part to mammalian IGFBP-1, similar to lower molecular mass IGFBPs reported in other species of fish. These results also suggest that a 20-kDa IGFBP is upregulated during fasting-induced growth inhibition of channel catfish and provide additional evidence of the conserved nature of the IGF-IGFBP-growth axis in fish.     

Fisheries and cage culture of three reservoirs in west Java, Indonesia; a case study of ambitious development and resulting interactions

Abstract The interactions between cage culture and wild fishery activities in three Indonesian reservoirs, Saguling, Cirata and Jatiluhur, of the greater Ciratum watershed, West Java, were evaluated using historical data and interviews with cage culture operators. In all three reservoirs, cage culture of common carp, Cyprinus carpio L., and later of common carp and Nile tilapia, Oreochromis niloticus (L.), were encouraged as an alternative livelihood for persons displaced by the impoundment. Currently, a two‐net culture system, locally known as ‘lapis dua’, in which in the inner cage (7 × 7 × 3 m) is used for common carp culture and the outer cage (7 × 7 × 5/7 m) is stocked with Nile tilapia, is practised. On average each cage is stocked with approximately 100 kg fingerlings each of common carp and Nile tilapia. The numbers of cages and production of cultured fish has increased in the reservoirs, but total and per cage production began to decline from about 1995 in Saguling from 2200 kg cage^?1 in 1989 to <500 kg cage^?1 in 2002, and in Cirata from a peak of approximately 2300 kg cage^?1 in 1995 to approximately 400 kg cage^?1 in 2002. In Jatiluhur, which has a considerably lower cage density, total fish production and production per cage has increased since 2000, and currently is approximately 4000 kg cage^?1, close to production in the early years of cage culture activities. The cage culture operations also resulted in substantial nutrient loading, estimated at 3.2, 15.2 and 3.1 t of nitrogen and 134, 636 and 128 kg of phosphorous per year in the maximum years of production for Saguling, Cirata and Jatiluhur reservoirs, respectively. In later years, when cage culture production was high, fish kills occurred in the cages, and in Jatiluhur reservoir coincided with a dramatic decline in wild fishery catches. An attempt is made to determine the maximum number of cages for each of the reservoirs that will bring long‐term sustainability of cage culture operations and the wild fisheries in the three reservoirs.     

Growth performance, feed efficiency and fatty acid composition of juvenile Murray cod, Maccullochella peelii peelii, fed graded levels of canola and linseed oil

In two independent experiments, the effects of dietary inclusion of canola and linseed oil were evaluated in juvenile Murray cod (Maccullochella peelii peelii, Mitchell) over a 112‐day period. In each experiment, fish received one of five semi‐purified diets in which the dietary fish oil was replaced with canola oil (Experiment A) or linseed oil (Experiment B) in graded increments of 25% (0–100%). Murray cod receiving the graded canola and linseed oil diets ranged in final weight from 112.7 ± 7.6 to 73.8 ± 9.9 g and 93.9 ± 3.6 to 74.6 ± 2.2 g, respectively, and exhibited a negative trend in growth as the inclusion level increased. The fatty acid composition of the fillet and liver were modified extensively to reflect the fatty acid composition of the respective diets. Levels of oleic acid (18:1 n‐9) and linoleic acid (18:2 n‐6) increased with each level of canola oil inclusion while levels of α‐linolenic acid (18:3 n‐3) increased with each level of linseed oil inclusion. The concentration of n‐3 highly unsaturated fatty acids in the fillet and liver decreased as the amount of vegetable oil in the diets increased. It is shown that the replacement of fish oil with vegetable oils in low fish meal diets for Murray cod is possible to a limited extent. Moreover, this study reaffirms the suggestion for the need to conduct ingredient substitution studies for longer periods and where possible to base the conclusions on regression analysis in addition to anova .     

Utilization of soybean meal as an alternative protein source in the Mediterranean yellowtail, Seriola dumerili

The availability of defatted soybean meal as a substitute for fish meal was evaluated in juvenile (450 g on average) yellowtail fed diets containing several levels of soybean meal (from 20 to 50%). After 153 days, liveweight averages were 980, 925, 795 and 670 g for fish fed diets in which fish meal was partially substituted with 20, 30, 40 and 50% soybean meal, and feed conversion ratios were 2.79, 3.09, 4.57 and 6.52, respectively. Regression analysis showed a negative effect of inclusion of soybean, although fish fed diets containing 20% and 30% of soybean did not present statistical differences and grew significantly more, and had a better feed conversion ratio, than fish fed 40 or 50% diets. Likewise, muscle protein level was lower and lipid content was higher in fish fed 20 or 30% soybean. No differences were obtained for protein digestibility coefficients of experimental diets.     

Relative bioavailability of zinc in supplemental inorganic and organic sources for Nile tilapia Oreochromis niloticus fingerlings

A 90‐day feeding experiment was conducted with sex reversed Nile tilapia (Oreochromis niloticus) fingerlings fed purified or practical diets supplemented with different zinc sources to evaluate fish growth performance and zinc and iron retention in fish bones, fillets, liver, skin and eyes. The relative bioavailability value (RBV) of zinc in the supplemental sources tested was also calculated. Fish were fed with isonitrogenous and isoenergetic purified or practical diets supplemented with 150 mg Zn kg^?1, as zinc sulphate monohydrate (ZnSO₄), zinc oxide (ZnO) or zinc amino acid complex (Zn‐AA). The feeding trial was conducted in 30, 50 L aquaria where four 0.66 ± 0.01 g (mean ± SD) fingerlings were initially stocked. No significant differences were observed for any growth performance variables (P > 0.05). In practical diets, only ZnSO₄ and ZnO presented bone zinc retention similar to that for the standard zinc source. Zinc concentration in the bone of fish fed practical diet supplemented with Zn‐AA (171 ± 3.62 μg g^?1) was significantly lower than that verified for the practical diets supplemented with the standard zinc source (200 ± 17.7 μg g^?1) or with ZnSO₄ (204 ± 19.9 μg g^?1). Assuming the concentration of zinc in bones as the response criterion, the supplemental zinc RBV from ZnSO₄ (105%) was higher than the RBV for Zn‐AA (95.1%) or ZnO (94.9%). Iron concentration in the bones of animals fed the non‐zinc‐supplemented purified diet was significantly higher than that observed for purified diet supplemented with Zn‐AA (P < 0,05). The results of the present work allowed us to conclude that ZnSO₄ in relation to ZnO or Zn‐AA was the supplemental zinc source with higher zinc bioavailability to Nile tilapia.     

Combined Influence of Mulches and Transplanting on Earliness and Yield of Muskmelon,Cucumis Melo L.

An investigation of the combined effect of mulching and transplanting muskmelons showed that transplanting increased early yield appreciably; mulching in conjunction with transplanting further increased earliness. Total yield also was increased by some treatments. Clear polyethylene (polythene), black polythene, and Kraft paper coated with clear polythene were evaluated as mulches on transplanted and field-seeded melons. Clear polythene generally induced greater early yields in field-seeded melons, but the response to black polythene, clear polythene and polythene-coated paper was comparable for transplanted melons. Waxed paper and aluminium foil also were tested as mulches for transplanted melons.     

Development and validation of a spectrophotometric method for quantification of total glucosinolates in cruciferous vegetables

Given their putative role in chemoprevention, validated methods are needed for quantification of total glucosinolates. Based on the colorimetric reaction of ferricyanide with 1-thioglucose, released by alkaline hydrolysis of glucosinolates, we developed a simple and sensitive method for spectrophotometric quantification of total glucosinolates in cruciferous vegetables. Lyophilized and ground vegetables are extracted with 80% boiling methanol. Extracted glucosinolates are isolated using a strong anion exchange column and then hydrolyzed with 2 N NaOH to release 1-thioglucose. Ferricyanide is added, and the decrease in absorbance is measured at 420 nm, with final values adjusted for background. Recovery of internal standard (sinigrin) was 107%. Intra- and interassay coefficients of variation were 5.4% and 15.8%, respectively. Dose response was linear with sinigrin and amount of plant material extracted (R(2) ≥ 0.99). Using sinigrin, the lower limit of quantification was 0.6 mg. This straightforward method may be an alternative to time-consuming and costly chromatographic methods.     

Influence of phenolic compounds on the mechanisms of pyrazinium radical generation in the Maillard reaction

The generation of pyrazinium radical cations during the early stages of the Maillard reaction has been previously demonstrated. In this study, the effect of food phenolic compounds [4-methylcatechol (4-MeC), (+)-catechin (CAT), and (-)-epigallocatechin-3-gallate (EGCG)] on the fate of these intermediates in Maillard model systems was investigated. Aqueous solutions containing either glyoxal + alanine (GO-A) or glycolaldehyde + alanine (GA-A) were treated with a concentration gradient of each phenolic compound, and quantitative analysis of the resulting pyrazinium radicals in these models was performed using electron paramagnetic resonance (EPR) spectroscopy. CAT and EGCG were observed to affect pyrazinium radical generation rates, in some cases either enhancing or suppressing formation depending on concentration, whereas the simple catechol (4-MeC) had no such effect. A mechanistic study was carried out by LC-MS, which suggested that under some conditions, CAT and EGCG react with imine intermediates via their A-rings, thus influencing the formation of the enaminol radical precursor and, ultimately, pyrazinium radicals. To the authors' knowledge, this is the first study demonstrating imine trapping by phenolic compounds under Maillard conditions and how such phenolic quenching reactions can alter pyrazinium radical formation.