Comparison between capillary electrophoresis and high performance liquid chromatography for the study of the occurrence of patulin in apple juice intended for infants

Apple juice samples intended for infants purchased in Navarra (Spain) have been analyzed for PAT occurrence. Two capillary electrophoresis methods, based on a MEKC and a CEC system, and an HPLC method were evaluated for the aforementioned study. The CEC system gave less satisfying separations and several practical problems, so samples have been analyzed by MEKC and HPLC. Both methods have been comparable in terms of recovery, precision, limits of detection, volume of organic solvents used and adequate selectivity with regard to PAT and HMF. The analysis time in HPLC has been slightly lower than in the MEKC methodology. The PAT levels obtained in apple juice by both validated methods showed a strong correlation (p < 0.001). Therefore, both methodologies are useful for the accurate quantification of patulin in this matrix.The PAT levels obtained in the 20 infant apple juices samples were in a range between <LOD and 29.6 μg L^?1, with a mean concentration of 8.0 μg L^?1 which implies a dietary intake estimation of 104 ng kg^?1 b.w. day^?1 considering a body weight of 10 kg and an apple juice consumption of 130 mL day^?1, 26% of the PMTDI recommended by JECFA.     

Studies on the protective role of lycopene against polychlorinated biphenyls (Aroclor 1254)-induced changes in StAR protein and cytochrome P450 scc enzyme expression on Leydig cells of adult rats

Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental contaminants that disturb normal endocrine functions, including gonadal functions in humans and mammals. PCBs (Aroclor 1254) - induced toxic manifestations are associated with the production of free radicals. Lycopene belongs to the group of natural carotenoids, which are found in many fruits, vegetables and other green plants. Lycopene, the most potent antioxidant protects against oxidative damage. The present study was conducted to elucidate the protective role of lycopene against Aroclor 1254-induced changes in Leydig cellular steroidogenic acute regulatory (StAR) protein, cytochrome P450 side chain cleavage (P450 scc) enzyme expression and 3β-hydroxy steroid dehydrogenase (3β-HSD) activity. The rats were divided into four groups. Each group consists of six animals. Group I rats were administered with corn oil intraperitoneally (i.p.) for 30 days. Group II rats were treated with Aroclor 1254 (i.p.) 2 mg kg^?1 body weight (bwt) day^?1 for 30 days. Group III rats were treated with Aroclor 1254 (i.p.) 2 mg kg^?1 bwt day^?1 along with simultaneous supplementation of lycopene 4 mg kg^?1 bwt day^?1 (gavage) for 30 days. Group IV rats administered with lycopene alone at the dose of 4 mg kg^?1 bwt day^?1 (gavage) for 30 days. After 24 h of the last treatment, animals were decapitated, blood was collected and serum testosterone level was estimated by radioimmunoassay (RIA). Testes were removed and Leydig cells were isolated in aseptic condition. StAR protein, cytochrome P450 scc enzyme expression were studied by Western blot analysis and 3β-HSD activity was estimated spectrophotometrically. Aroclor 1254 treatment significantly reduced the serum testosterone level. Simultaneous supplementation of lycopene maintained the serum testosterone to near normal. Aroclor 1254 exposure decreased Leydig cellular StAR protein, cytochrome P450 scc enzyme expression and activity of 3β-HSD. However, simultaneous supplementation of lycopene improved Leydig cellular StAR protein, cytochrome P450 scc expression and activity of 3β-HSD. These results suggested that lycopene have ameliorative role against Aroclor 1254 induced Leydig cell dysfunction.     

In vivo effects of deoxynivalenol (DON) on innate immune responses of carp (Cyprinus carpio L.)

Deoxynivalenol (DON) is one of the most important members of Fusarium toxins since it often can be found in relevant concentrations in animal feeds. The effects of this group of toxins on fish are mostly unknown. The present study shows results from a feeding trial with carp (Cyprinus carpio L.) using three different concentrations of DON (352 μg kg⁻¹, 619 μg kg⁻¹, and 953 μg kg⁻¹ final feed, respectively) which are comparable to levels found in commercial fish feeds. Effects on growth and mass of fish were not observed during this 6 weeks lasting experiment. Only marginal DON concentrations were found in muscle and plasma samples. Blood parameters were not influenced although smaller erythrocytes occurred in fish treated with 352 μg kg⁻¹ DON. Analysis of antioxidative enzymes in erythrocytes showed increased superoxid dismutase and catalase activities in fish fed the low-dose feed. Immunosuppressive effects of DON were confirmed whereby cytotoxic effects on immune cells only partly explained the impairment of innate immune responses. Exact polarization of the immune system into pro-inflammatory or anti-inflammatory responses due to DON exposure should be clarified in further experiments, especially since the current results raise concern about impaired immune function in fish raised in aquaculture.     

LC–MS/MS determination of the isomeric neurotoxins BMAA (β-N-methylamino-l-alanine) and DAB (2,4-diaminobutyric acid) in cyanobacteria and seeds of Cycas revoluta and Lathyrus latifolius

Since diverse taxa of cyanobacteria has been linked to biosynthesis of BMAA, a controversy has arisen about the detection of neurotoxic amino acids in cyanobacteria. In this context, a novel LC–MS/MS method was developed for the unambiguous determination of β-N-methylamino-l-alanine (BMAA) and 2,4-diaminobutyric acid (DAB) in cyanobacteria and selected plant seeds. Both neurotoxic and non-proteinogenic amino acids were analyzed without derivatization considering the total concentration of the free and protein-bound form. The investigation of overall 62 cyanobacterial samples of worldwide origin by application of this method revealed the absence of BMAA, whereas seeds of Cycas revoluta contained 6.96 μg g^?1 of free BMAA. In contrast, the isomer DAB was confirmed in 16 cyanobacterial samples in concentrations of 0.07–0.83 μg g^?1,whereof one sample is distributed as nutritional supplement. In addition, seeds of Lathyrus latifolius contained 4.21 μg g^?1 of free DAB. Limits of detection were for BMAA < 1.0 μg g^?1 in the cyanobacterial matrix and < 0.14 μg g^?1 in angiosperm seeds. DAB exhibits higher sensitivities of <0.06 μg g^?1 in cyanobacteria and <0.008 μg g^?1 in angiosperm seeds. The highly specific analysis method with increased detection sensitivity eliminates the disadvantages of derivatization-based methods to be discussed.     

The pharmacokinetics of orally administered S-carboxymethyl-l-cysteine in the dog,calf and sheep

The aim of this study was to investigate the feasibility of employing S-carboxymethyl-l-cysteine as a treatment of chronic obstructive pulmonary disease in dogs. To this end the pharmacokinetic parameters of orally administered S-carboxymethyl-l-cysteine were determined in the dog, cow and sheep. Six healthy beagle dogs, six endogenous Greek sheep and four Holstein Fresian calves were orally dosed with 10 mg/kg body weight of S-carboxymethyl-l-cysteine. No significant differences in T_max and T_1/2 were reported between the species. However, significantly higher AUC_(0–last), 21.56 ± 6.67 μg h ml^?1 and AUC_(0–∞), 21.63 ± 6.68 μg h ml^?1 were seen in the dogs compared to the sheep and calves. The calculated V_D was significantly higher in the sheep (10.4 ± 2.7 L kg^?1) and the calves (3.8 ± 0.7 L kg^?1) compared to the dogs (1.0 ± 0.6 L kg^?1). The rank order of increasing C_L was sheep (3.4 ± 2.7 L h^?1 kg^?1) > calves (2.7 ± 0.4 L h^?1 kg^?1) > dogs (0.5 ± 0.2 L h^?1 kg^?1). The result for the dogs was significantly lower that the calculated C_L for the sheep and calves.All these results indicate that the oral administration of S-carboxymethyl-l-cysteine may be useful during the therapeutic management of chronic obstructive pulmonary disease in dogs.     

Lipid-core nanocapsules restrained the indomethacin ethyl ester hydrolysis in the gastrointestinal lumen and wall acting as mucoadhesive reservoirs

The aim of this work was to investigate if the indomethacin ethyl ester (IndOEt) released from lipid-core nanocapsules (NC) is converted into indomethacin (IndOH) in the intestine lumen, intestine wall or after the particles reach the blood stream. NC–IndOEt had monomodal size distribution (242 nm; PDI 0.2) and zeta potential of ?11 mV. The everted rat gut sac model showed IndOEt passage of 0.16 μmol m^?2 through the serosal fluid (30 min). From 15 to 120 min, the IndOEt concentrations in the tissue increased from 6.13 to 27.47 μmol m^?2. No IndOH was formed ex vivo. A fluorescent-NC formulation was used to determine the copolymer bioadhesion (0.012 μmol m^?2). After NC–IndOEt oral administration to rats, IndOEt and IndOH were detected in the gastrointestinal tract (contents and tissues). In the tissues, the IndOEt concentrations decreased from 459 to 5 μg g^?1 after scrapping, demonstrating the NC mucoadhesion. In plasma (peripheric and portal vein), in spleen and liver, exclusively IndOH was detected. In conclusion, after oral dosing of NC–IndOEt, IndOEt is converted into IndOH in the intestinal lumen and wall before reaching the blood stream. The complexity of a living system was not predicted by the ex vivo gut sac model.     

Urinary analysis reveals high deoxynivalenol exposure in pregnant women from Croatia

In this pilot survey the levels of various mycotoxin biomarkers were determined in third trimester pregnant women from eastern Croatia. First void urine samples were collected and analysed using a “dilute and shoot” LC–ESI–MS/MS multi biomarker method. Deoxynivalenol (DON) and its metabolites: deoxynivalenol-15-glucuronide and deoxynivalenol-3-glucuronide were detected in 97.5% of the studied samples, partly at exceptionally high levels, while ochratoxin A was found in 10% of the samples. DON exposure was primarily reflected by the presence of deoxynivalenol-15-glucuronide with a mean concentration of 120 μg L⁻¹, while free DON was detected with a mean concentration of 18.3 μg L⁻¹. Several highly contaminated urine samples contained a third DON conjugate, tentatively identified as deoxynivalenol-7-glucuronide by MS/MS scans. The levels of urinary DON and its metabolites measured in this study are the highest ever reported, and 48% of subjects were estimated to exceed the provisional maximum tolerable daily intake (1 μg kg⁻¹ b.w.).     

Silver nanoparticle induced toxicity to human sperm by increasing ROS(reactive oxygen species) production and DNA damage

Silver nanoparticles (AgNPs) have been used in medical products and industrial coatings, due to their antimicrobial properties. Excessive use of AgNPs can have adverse effects on the human body, however, their toxicity characteristics to human sperm and the potential mechanisms are not entirely clear. In this study, we exposed human sperm to different doses of AgNPs (0, 50 μg ml⁻¹, 100 μg ml⁻¹, 200 μg ml⁻¹ or 400 μg ml⁻¹) for various times (15 min, 30 min, or 60 min), followed by analyses of the sperm viability, motility and the ratio of abnormal to normal sperm.Then, transmission electron microscopy(TEM) was used to explore the sperm ultrastructural characteristics. Reactive oxygen species production and DNA fragmentation were tested using standard kits and the sperm chromatin dispersion method, respectively. The results showed a dose- and time-dependent decline in sperm viability and motility and an increased ratio of abnormal to normal sperm after 30 min and 60 min of exposure to AgNPs at 200 μg ml⁻¹ and 400 μg ml⁻¹. The most common abnormalities were sperm heads with disrupted chromatin or absent acrosomes, bent tails, and curved mid-pieces. The ultrastructural characteristics of AgNP-treated sperm included disrupted, swollen, granular and vacuolar defects of the chromatin. In addition, ROS(reactive oxygen species)production and DNA fragmentation were markedly increased after 60 min of exposure to AgNPs at 200 μg ml⁻¹ and 400 μg ml⁻¹. Our results indicated that AgNPs caused detrimental changes in human sperm characteristics, and the excessive use of AgNPs should be carried out with caution.     

Evaluation of estrogenic activity in animal diets using in vitro assay

A yeast estrogen bioassay (RIKILT REA) was in-house validated for feed on the 5 μg 17β-estradiol-equivalents per kg level according to EC Decision 2002/657/EC. All the performance characteristics met the criteria as defined in the Decision and the REA is able to detect 17β-estradiol in animal feed at a low level of 1.15–2 μg kg⁻¹. Subsequently, the developed and validated procedure was applied to determine the estrogenic activity in 24 feed samples intended for food producing animals, pets and laboratory animals. Two batches of rodent diet Murigran and one dog feed have been presented as a suspect, i.e. gave responses above the determined decision limit (CCα) and detection capability (CCβ). In assessing the performance of the estrogenic activity in these diets evaluated by comparison with the 17β-estradiol calibration curve, 17β-estradiol-equivalence levels of 7.07 μg EEQ kg⁻¹ and 9.54 μg EEQ kg⁻¹ in two batches of rodent diet and 5.3 μg EEQ kg⁻¹ in dog feed have been established. The activities observed in the rodent feed could be explained by chemical analysis, revealing high amounts of genistein, daidzein and trace amounts of zearalenone. In addition, the estrogenic activity in one of rodent feed was above the established CCα, but below the CCβ values established and all other samples showed no estrogenic activity with responses below the CCα value, which corresponds to levels below 2 μg EEQ kg⁻¹.     

Industrial release of fluoroquinolones (FQs) in the waste water bodies with their associated ecological risk in Pakistan

The unchecked production and use of fluoroquinolones (FQs) for the treatment of infections in human and livestock has increased in Pakistan, which resulted in large amount of antibiotics in water bodies. In the current study, the prevalence and associated ecological risk of three FQs were investigated in waste-water bodies and sludge samples of Kahuta and Hattar industrial zones. The average concentrations of ciprofloxacin (CIP), enrofloxacin (ENR) and levofloxacin (LEV) in the waste-water samples were slightly higher in Kahuta (i.e. 58, 32.9, and 36.7 μg L⁻¹ respectively), than those in Hattar sites (i.e. 42.1, 41.2, and 48.9 μg L⁻¹ respectively). However, the concentrations of CIP, ENR and LEV in the sludge samples were significantly higher (i.e. 159; 153 and 164 μg kg⁻¹ respectively) in Hattar sites, compared to those in Kahuta sites (i.e. 129, 58 and 91 μg kg⁻¹ respectively). The uses of FQs in the health sector resulted in water pollution and poses the ecological risk to aquatic organisms. The individual risk associated with CIP was highest in Kahuta industrial sites for green algae ranging (2900–9100) followed by M. aeruginosa (5800–18200), cyanobacteria (580–18204) and invertebrates (24.2–75.8). These values suggested that the prevalence of antibiotics in the waste-disposal sites could be potential risk for the aquatic ecosystem, and harmful to biodiversity.     

Human health risk assessment and dietary intake of organochlorine pesticides through air,soil and food crops (wheat and rice) along two tributaries of river Chenab,Pakistan

To assess the organochlorine pesticides (OCPs) contamination and their probable hazardous effects on human health; cereal crops (wheat and rice; n = 28) agricultural soil (n = 28) and air (n = 6) samples were collected from Gujranwala division, Punjab Province, Pakistan. ∑OCPs concentration ranged between 123 and 635 pg m⁻³, 31 and 365 ng g⁻¹ (dw), 2.72 and 36.6 ng g⁻¹ (dw), 0.55 and 15.2 ng g⁻¹ (dw) for air, soil, rice and wheat samples, respectively. DDTs were the predominant over other OCPSs detected from screened samples while the source apportionment analysis suggested the new inputs of DDTs in the study area. EDI (estimated daily intake) of ∑OCPs through rice and wheat was found 39 and 40 ng kg⁻¹ day⁻¹, respectively. Hazard ratios (HRs) on the basis 95th percentile concentrations were exceeding the integrity for most of the investigated OCP in rice and wheat. The results revealed that there is a severe risk to the human population of the study area through consumption of contaminated cereal crops.     

Oxidative stress responses in zebrafish Danio rerio after subchronic exposure to atrazine

Atrazine is one of the most used pesticides all over the world and it is frequently detected in surface water. The aim of this study was to investigate if zebrafish exposure to atrazine could induce oxidative stress and changes in detoxifying system. Juvenile fish were exposed to sublethal concentrations of 0.3, 3, 30, or 90 μg L⁻¹ for 28 days. The level of oxidized lipids increased in experimental groups exposed to atrazine at 30 and 90 μg L⁻¹ compared to control. Activity of glutathione S-transferase decreased in group with the highest concentration compared to control. A significant decline was observed in catalase activity in all experimental groups compared to control. Activity of superoxide dismutase increased only in experimental group exposed to atrazine at 30 μg L⁻¹ compared to control. Activity of glutathione peroxidase and reductase (GR) increased in experimental groups exposed to atrazine at 0.3 (only for GR activity) and 90 μg L⁻¹ compared to control. Our results showed that atrazine exposure had profound influence on the oxidative stress markers and detoxifying enzyme of the exposed zebrafish. The changes in antioxidant enzyme activities could be an adaptive response to protect the fish from the atrazine-induced toxicity.     

Toxicological effects of clofibric acid and diclofenac on plasma thyroid hormones of an Indian major carp,Cirrhinus mrigala during short and long-term exposures

In the present investigation, the toxicity of most commonly detected pharmaceuticals in the aquatic environment namely clofibric acid (CA) and diclofenac (DCF) was investigated in an Indian major carp Cirrhinus mrigala. Fingerlings of C. mrigala were exposed to different concentrations (1, 10 and 100 μg L⁻¹) of CA and DCF for a period of 96 h (short term) and 35 days (long term). The toxic effects of CA and DCF on thyroid hormones (THs) such as thyroid stimulating hormone (TSH), thyroxine (T₄) and triiodothyronine (T₃) levels were evaluated. During the short and long-term exposure period TSH level was found to be decreased at all concentrations of CA (except at the end of 14^th day in 1 and 10 μg L^−l and 21^st day in 1 μg L^−l) whereas in DCF exposed fish TSH level was found to be increased when compared to control groups. T₄ level was found to be decreased at 1 and 100 μg L^−l of CA exposure at the end of 96 h. However, T₄ level was decreased at all concentrations of CA and DCF during long-term (35 days) exposure period. Fish exposed to all concentrations of CA and DCF had lower level of T₃ in both the treatments. These results suggest that both CA and DCF drugs induced significant changes (P < 0.01 and P < 0.05) on thyroid hormonal levels of C. mrigala. The alterations of these hormonal levels can be used as potential biomarkers in monitoring of pharmaceutical drugs in aquatic organisms.     

Decreased analgesic effect of morphine,but not buprenorphine,in patients with advanced P-glycoprotein+ cancers

BackgroundP-glycoprotein (P-gp) is expressed on the blood-brain barrier (BBB) and acts as a transporter regulating the analgesic effect of morphine. The P-gp is also expressed by different types of tumors. The aim of this study was to determine the potential association of the P-gp expression in malignant tumors with analgesic effects in patients.MethodsThe P-gp expression in 120 malignant tumors was examined by immunohistochemistry. The analgesic responses of individual patients to morphine and buprenorphine (BNP) were evaluated by visual analog scale (VAS). The levels of plasma morphine and BNP were determined by HPLC.ResultsWe found that there was no significant difference in the values of VAS between patients with P-gp⁺ and P-gp^?malignant tumors in responses to 0.000025 g × kg^?2 of BNP administered by patient-controlled intravenous analgesia (PCIA), accompanied by similar levels of plasma BNP in those patients. In contrast, the values of VAS in response to 0.00075 g × kg^?2 of morphine in patients with P-gp⁺ tumors were significantly greater than those in the patients with P-gp^? tumors, although similar levels of plasma morphine were detected in both groups of patients. Furthermore, treatment with a higher dose (0.0011 g × kg^?2) of morphine effectively controlled pain in those with P-gp⁺ tumors.ConclusionOur data indicated that patients with P-gp⁺ tumors required a higher dose of morphine to achieve an analgesic effect and that the P-gp expression in tumors may be valuable for predicting the analgesic responses of patients with severe pain to morphine.     

Inhalation exposure or body burden? Better way of estimating risk – An application of PBPK model

We aim to establish a new way for estimating the risk from internal dose or body burden due to exposure of benzene in human subject utilizing physiologically based pharmacokinetic (PBPK) model. We also intend to verify its applicability on human subjects exposed to different levels of benzene. We estimated personal inhalation exposure of benzene for two occupational groups namely petrol pump workers and car drivers with respect to a control group, only environmentally exposed.Benzene in personal air was pre-concentrated on charcoal followed by chemical desorption and analysis by gas chromatography equipped with flame ionization detector (GC-FID). We selected urinary trans,trans-muconic acid (t,t-MA) as biomarker of benzene exposure and measured its concentration using solid phase extraction followed by high performance liquid chromatography (HPLC).Our estimated inhalation exposure of benzene was 137.5, 97.9 and 38.7 μg/m³ for petrol pump workers, car drivers and environmentally exposed control groups respectively which resulted in urinary t,t-MA levels of 145.4 ± 55.3, 112.6 ± 63.5 and 60.0 ± 34.9 μg g⁻¹ of creatinine, for the groups in the same order.We deduced a derivation for estimation of body burden from urinary metabolite concentration using PBPK model. Estimation of the internal dose or body burden of benzene in human subject has been made for the first time by the measurement of t,t-MA as a urinary metabolite using physiologically based pharmacokinetic (PBPK) model as a tool. The weight adjusted total body burden of benzene was estimated to be 17.6, 11.1 and 5.0 μg kg⁻¹ of body weight for petrol pump workers, drivers and the environmentally exposed control group, respectively using this method. We computed the carcinogenic risk using both the estimated internal benzene body burden and external exposure values using conventional method. Our study result shows that internal dose or body burden is not proportional to level of exposure rather have a non-linear relationship. At a higher exposure level such as for occupational exposure of petrol pump workers and drivers, the conventionally estimated risk is higher than risk estimated from internal body burden. Likewise, for environmental exposure the conventional risk estimation predict lower level than estimated in our study. This emphasizes the importance of body burden and to consider it as a key parameter while estimating health risk at varying level of exposure.     

Using transdermal iontophoresis to increase granisetron delivery across skin in vitro and in vivo: Effect of experimental conditions and a comparison with other enhancement strategies

The objectives of the study were (i) to investigate the effect of experimental parameters on the iontophoretic transport of granisetron, (ii) to identify the relative contributions of electromigration (EM) and electroosmosis (EO), (iii) to determine the feasibility of delivering therapeutic amounts of drug for the treatment of chemotherapy-induced nausea and vomiting and (iv) to test the in vitro results in a simple animal model in vivo. Preliminary in vitro studies using aqueous granisetron formulations investigating the effect of drug concentration (5, 10, 20 and 40 mM) and current density (0.1, 0.2, 0.3 mA cm^?2) were performed using porcine ear skin. As expected, cumulative delivery in vitro at the 20 and 40 mM concentrations was significantly greater than that at 5 and 10 mM, which were not statistically different (p < 0.05). Increasing the applied current density from 0.1 to 0.3 mA cm^?2 resulted in a ～4.2-fold increase in iontophoretic flux. Furthermore, in the absence of Na⁺ in the formulation, no dependence of iontophoretic flux on drug concentration was reported (at a granisetron concentration of 40 mM, the transport rate was 2.93 ± 0.62 μg cm^?2 min^?1). Co-iontophoresis of acetaminophen was used to show that EM was the predominant transport mechanism accounting for 71–86% of total granisetron delivery. In vivo studies in Wistar rats (40 mM granisetron; application of 0.3 mA cm^?2 for 5 h with Ag/AgCl electrodes and salt bridges) showed an average iontophoretic input rate (k_input) of 0.83 ± 0.26 μg min^?1 and a maximum plasma concentration (C_max) of 0.092 ± 0.004 μg ml^?1. Based on these results and given the known pharmacokinetics, transdermal iontophoresis could achieve therapeutic drug levels for the management of chemotherapy-induced emesis using a reasonably sized (4–6 cm²) patch.     

Sustainable succinic acid production from rice husks

In this study, an investigation was carried out into the production of succinic acid by Actinobacillus succinogenes using the residual biomass rice husks as a sustainable carbon source. The rice husks were submitted to acid hydrolysis in autoclave and in a pressurized polytetrafluorethylene vessel. The hydrolysis conditions were optimized with the aid of a factorial design. The best results were obtained with a pressurized reactor using HCl 2.2% (v v^?1), at a temperature of 174 °C (59 bar), 46 min reaction time, and producing 19.0 g L^?1 glucose and 3.01 g L^?1 xylose. The hydrolysate was detoxified through a combination of pH regulation and adsorption on active carbon; it was subsequently, fermented in anaerobic medium at 37 °C; the nutrient concentration and the agitation speed were also optimized by factorial design. After 54 h static fermentation of the rice husks hydrolysate, supplemented with 8.40 g L^?1 yeast extract and 1.40 g L^?1 NaHCO₃, an amount of 12.5 g succinic acid L^?1 was produced, which corresponds to a yield of 59.9%. This confirms that, rice husks can definitely be used as substrate to produce succinic acid and other priority chemicals     

The application of co-melt-extruded poly(ε-caprolactone) as a controlled release drug delivery device when combined with novel bioactive drug candidates: Membrane permeation and Hanson dissolution studies

Eight bioactive drug compounds (abamectin, amoxicillin, dexamethasone, dexamethasone valerate, ketoprofen, melatonin, oestradiol 17β, and oestradiol benzoate) were combined via melt extrusion and disc pressing processes with a polycaprolactone (PCL) matrix and were then evaluated and compared via membrane diffusion and Hanson dissolution studies. This investigation was to determine the potential of this matrix to act as a controlled release drug delivery vehicle for a number of drugs not previously combined with PCL in a melt extrusion mix. The inclusion of the progesterone/PCL system, for which the drug release behaviour has been well studied before was intended for comparison with the PCL systems incorporating drugs that have received little research attention in the past. Initial studies centred on an evaluation of the permeation ability of the bioactive drugs dissolved in aqueous cyclodextrin solutions through a poly(ε-caprolactone) (PCL) membrane using Valia-Chien side-by-side cells. Permeation rates were mostly low and found to range from 0 to 122 μg h^?1 with only ketoprofen, melatonin, and progesterone displaying rates exceeding 20 μg h^?1. Hanson dissolution release profiles in aqueous alcohol were subsequently measured for the 9 melt extruded PCL/drug combinations and led to Hanson release rates of 0–556 μg cm^?2 h^?0.5 with dexamethasone, dexamethasone valerate, ketoprofen, melatonin, and progesterone giving values exceeding 100 μg cm^?2 h^?0.5. A number of drugs such as the dexamethasones probably performed better than they did in the permeability rate measurements because of the less polar aqueous alcoholic solvent used. In searching for useful correlations between the drug physicochemical properties and release rate, only a moderate correlation (R²=0.5675) between Hanson dissolution release rate and permeation rate was found. This suggests that the release rate and the permeation are both controlled by the rate of drug diffusion through the PCL with release rate involving an additional dissolution process (of the drug) before permeation occurs accounting for the moderate correlation. In general, of the eight drugs considered, it was clear that the oestradiol-based drugs, abamectin, and amoxicillin were generally not suited to drug delivery via PCL under the conditions used. However, ketoprofen was found to be very suitable as a drug candidate for melt extrusion with PCL with dexamethasone valerate, dexamethasone, and melatonin also showing potential as candidates though to a much lesser extent.     

Toxicity of cylindrospermopsin in human lymphocytes: Proliferation,viability and cell cycle studies

The global expansion of cylindrospermopsin (CYN) producing cyanobacteria in surface freshwater increases the risk of human exposure and poisoning. Following ingestion, CYN is transported with blood in general circulation to the liver and kidneys, and can potentially interact with immune system cells. In the present study, we investigated whether CYN (0.01–1.0 μg ml⁻¹) can alter the function of human peripheral blood lymphocytes isolated from healthy donors. It was found that CYN demonstrates significant antiproliferative activity in lymphocytes during different phases of their activation. The most remarkable effects (decrease by > 90%) were observed in lymphocytes exposed to 1 μg ml⁻¹ CYN at the beginning of activation. Further analyses revealed a cell-cycle arrest at G0/G1 and prolonged S phase in lymphocytes undergoing activation and significant apoptosis inducement in activated cells. Reduced abilities to fight pathogenic microorganisms or malignant cells should be taken into consideration in CYN exposure and risk assessments.     

Influence of experimentally induced fever on the disposition of cefpirome in buffalo calves

The influence of Escherichia coli endotoxin-induced fever on the disposition of cefpirome was investigated in five male buffalo calves following a single intravenous dose of 10 mg kg⁻¹. Blood samples were collected from 1 min to 24 h of drug administration. The drug concentration in plasma was estimated by microbiological assay using E. coli as a test organism. The disposition of cefpirome followed two-compartment open model and the drug was detected above the minimum inhibitory concentration in plasma up to 12 h. The Vd_area and AUC were 0.75 ± 0.01 L kg⁻¹ and 35.1 ± 0.46 μg ml⁻¹ h, respectively. The elimination half-life of 1.81 ± 0.009 h and Cl_B of 0.29 ± 0.004 L kg⁻¹ h⁻¹ reflected rapid elimination and body clearance of cefpirome in febrile buffalo calves. Based on the results, a satisfactory dosage regimen of cefpirome in febrile buffalo calves was calculated to be 6 mg kg⁻¹ to be repeated at 8 h intervals.