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.     

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.     

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.     

Dietary fumonisin exposure in a rural population of South Africa

A validated culturally specific dietary assessment method was used to determine the habitual maize intakes of black Xhosa-speaking Africans living in the Centane region of the Eastern Cape Province to assess their exposure to the carcinogenic fumonisin mycotoxins. The mean total dry weight maize intakes of home-grown, commercial or combined (both maize sources) were 474, 344, 462 g day^?1, respectively. When considering the total mean levels of fumonisin in home-grown maize (1142 μg kg^?1) and commercial maize (222 μg kg^?1), the probable daily intakes (PDI’s), expressed as μg kg^?1 body weight day^?1 were 12.1 (95%CI: 0.3–4926.5) and 1.3 (95%CI: 1.0–1.8) for men and 6.7 (95%CI: 1.0–457.8) and 1.1 (95%CI: 0.9–1.3) for women, consuming home-grown and commercial maize, respectively. Based on the different maize-based beer drinking frequencies the PDI’s varied between 6.9 and 12.0 μg kg^?1/drinking event. Depending on the maize intake patterns an exposure “window” exists where fumonisin exposure is below the recommended group provisional maximum tolerable daily intake (PMTDI) for fumonisins of 2 μg kg^?1 bw day^?1. The assessment of fumonisin exposure and development of preventative strategies depend, not only the accurate determination of total fumonisin levels in maize, but also on the distinct dietary patterns of a specific population.     

Chemical state of heterocyclic aromatic amines in grilled beef: Evaluation by in vitro digestion model and comparison of alkaline hydrolysis and organic solvent for extraction

During grilling of the roast beef the following heterocyclic aromatic amines were found: IQ = 200.6 ng 100 g⁻¹, MeIQx = 719.8 ng 100 g⁻¹, MeIQ = 532.9 ng 100 g⁻¹, 4.8-diMeIQx = 755.4 ng 100 g⁻¹, norharmane = 507.0 ng 100 g⁻¹, harmane = 1952.6 ng 100 g⁻¹, Phe-P 1 = 263.7 ng 100 g⁻¹, Trp-P 2 = 559.2 ng 100 g⁻¹, PhIP = 1179.8 ng 100 g⁻¹ and AαC = 51.7 ng 100 g⁻¹. Their content was tested by using the method based on alkaline hydrolysis of the sample and the method based on solvent extraction of the grilled meat samples at different temperatures (without hydrolysis). The study showed that the heterocyclic aromatic amines produced during the grilling of beef are in a free form and chemically or physico-chemically bonded. The chemical forms of HAA formed in food have never been studied. For the purpose of the partial confirmation that HAA may be chemically or physico-chemically bonded, grilled beef samples were digested in vitro in model segments of the human digestive tract. Digestive enzymes, particularly proteolytic enzymes caused a statistically significant increase of free HAA determined by using solvent extraction without prior chemical hydrolysis of the sample.     

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.     

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.     

Ecotoxicity of veterinary enrofloxacin and ciprofloxacin antibiotics on anuran amphibian larvae

The ecological risks posed by two β-diketone antibiotics (DKAs, enrofloxacin, ENR and ciprofloxacin, CPX), characterized by their long persistence in aqueous environments and known deleterious effect on model organisms such as zebrafish were analysed using Rhinella arenarum larvae. Sublethal tests were conducted using environmentally relevant concentrations of both ENR and CPX (1–1000 μg L⁻¹) under standard laboratory conditions for 96 h. Biological endpoints and biomarkers evaluated were body size, shape, development and growth rates, and antioxidant enzymes (glutathione-S-transferase, GST; Catalase, CAT). Risk assessment was analysed based on ration quotients (RQ). The size and shape measurements of the larvae exposed to concentrations greater than 10 μg L⁻¹ of CPX were lower compared to controls (Dunnett post hoc p < 0.05) and presented signs of emaciation. Concentrations of 1000 μg L⁻¹of CPX induced GST activity, in contrast with inhibited GST and CAT of larvae exposed to ENR. Risk assessments indicated that concentrations greater than or equal to10 μg L⁻¹ of CPX and ENR are ecotoxic for development, growth, detoxifying, and oxidative stress enzymes. It is suggested that additional risk assessments may provide evidence of bioaccumulation of CPX and ENR in tissues or organs of amphibian larvae by mesocosm sediment test conditions. Finally, intestinal microbiome studies should be considered to establish the mechanisms of action of both antibiotics.     

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.).     

Removal of a textile dye using photovoltaic electrocoagulation

The main objective of this study was to investigate the operation of a continuous photovoltaic electrocoagulation process (PVEC) comprising an electrocoagulation (EC) part provided with aluminum electrodes and a settling zone, for the removal of a textile dye: the overall EC cell had a volume of 8.5 L. The effect of the operating parameters has been followed, e.g. inlet pH and dye concentration, residence time, current density, solar irradiance and energy consumption.The results showed that when the inlet concentration was increased from 50 to 1400 mg L^?1 and for the following operating conditions: current density ranging from 100 to 400 A m^?2, inlet flow rate at 15 L h^?1, electrode gap of 1 cm, inlet pH near 7, the removal rates of the color and turbidity were decreased from 96% to 87% and from 96% to 93%, respectively. Use of the photovoltaic cell in the place of the electric supply allowed to reach more than 99% of elimination of turbidity and 95% of the color when the initial concentration of the dye was 1400 mg L^?1.The specific electrical energy consumption was found at 16 kWh per kilogram of removed dye for EC using direct current, and at comparable levels upon use of photovoltaic cells. The consumption of the electrodes is at comparable levels for the two sources of energy, respectively at 0.45 and 0.6 kg Al per kg of removed dye).     

Extractive spectrophotometric assay of cyclizine in a pharmaceutical formulation and biological fluids

Two highly sensitive and simple spectrophotometric methods were developed to quantitate the drug cyclizine (CYC) in its pure form and in a pharmaceutical formulation. The two methods involved ion-associate formation reactions (method A) with mono-acid azo dyes, i.e., sudan (I) and sudan (II), as well as ion-pair reactions (method B) with bi-azo dyes, i.e., sudan (III), sudan (IV) and sudan red 7B (V). The reactions were extracted with chloroform, and the extraction products were quantitatively measured at 480, 550, 500, 530 and 570 nm using reagents I–V, respectively. The reaction conditions were monitored and optimised. The Beer plots for reagents I–V showed linear relationships for the concentrations of 4.2–52.0, 5.4–96.0, 3.5–43.0, 4.4–80.0 and 0.6–18.0 μg mL^?1, respectively, with molar absorptivities of 2.2 × 10⁴, 4.1 × 10⁴, 3.6 × 10⁴, 2.5 × 10⁴ and 1.3 × 10⁴ L mol^?1 cm^?1, respectively. Sandell sensitivities and detection limits were calculated and analysed. The implementation of the two methods to the analysis of a commercial tablet (Valoid) succeeded, and the recovery study suggested that there was no interference from common excipients in the tablet. Regarding the accuracy and precision of the methods, a statistical comparison of the results was performed using Student’s t-test and the F-test at the 95% confidence level. The accuracy and precision of the proposed methods were not significantly different.     

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.     

Investigation of lead contents in lipsticks by solid sampling high resolution continuum source electrothermal atomic absorption spectrometry

In this study, the lead contents of different kinds of lipsticks were determined by solid sampling high resolution continuum source electrothermal atomic absorption spectrometry (SS-HR-CS ET AAS) and the results were compared with those obtained after microwave-assisted acid digestion of the samples. The experimental parameters for solid sampling such as the maximum amount of sample on the platforms of solid autosampler, graphite furnace program were optimized. Samples were directly loaded on the platforms of solid autosampler between 0.25 and 2.0 mg and lead was determined applying 800 °C for pyrolysis and 2100 °C for atomization. Under optimized conditions, interference-free determination could be performed using aqueous standards. The LOD and the characteristic mass were 21.3 and 12.6 pg, respectively. The lead in the same lipstick samples was determined after microwave-assisted acid digestion and compared with those found by solid sampling. Mostly, there was no significant difference between the lead concentrations found by the two techniques. The lead in 25 lipstick samples with different properties were 0.11–4.48 ng mg^?1 which were not significantly different from those (<0.026–7.19 ng mg^?1) reported by FDA for around 400 samples.     

Effectiveness of biopesticides in enhancing paddy growth for yield improvement

There is an urgent need to enhance the productivity of irrigated paddy fields to increase the rice production that meets population growth. The focus of this study is to investigate the effectiveness of biopesticides in enhancing the paddy growth for yield improvement after controlling the pest and rice diseases. This study aims to determine either one or two types of biopesticides should be used in paddy cultivation. Thus, three conditions were adopted in paddy cultivation at the insect house as follows; T1 where the paddy was sprayed using BV500WS and BV612EC to study the effectiveness of the biopesticides, T2 where the paddy was sprayed using BV500WS only and C1 where the paddy was cultivated following the conventional technique as a control. BV500WS was sprayed into T1 and T2 on the first day of paddy growth while BV612EC was sprayed later into T1, at 55 and 67 days of paddy cultivation a week after releasing the brown planthopper (BPH). Based on the analysis of correlation obtained for each growth, application of BV500WS and BV612EC of T1 resulted in better performance in terms of height of plant, number of tillers, width of leaves, and number of leaves compared to T2 and C1. The excellence performance of plant growth at T1 produced the highest paddy yield of 2304.20 ± 491.42 g^?2, while T2 produced comparable yield as C1 which are 663.88 ± 128.41 g^?2 and 665.42 ± 183.30 g^?2 respectively. Hence, organic plants based biopesticides are successful in enhancing the plant growth of paddy and ultimately increase the paddy yield.     

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.     

Activity of the enzymes of the antioxidative system in cadmium-treated Oxya chinensis (Orthoptera Acridoidae)

One purpose in this research was to determine the toxic effects of Cd on antioxidant enzymes of Oxya chinensis (Orthoptera: Acridoidae). Changes in the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and guaiacol peroxidase (GPx) were measured in O. chinensis insects injected with Cd²⁺. Fifth-nymphs of O. chinensis insects were injected with Cd²⁺ at different concentrations (0, 0.55 × 10⁻⁴, 1.10 × 10⁻⁴, 1.65 × 10⁻⁴, 2.20 × 10⁻⁴, and 2.75 × 10⁻⁴ g g⁻¹). An increase in SOD activity in O. chinensis was observed at 1.10 × 10⁻⁴ to 2.75 × 10⁻⁴ g g⁻¹ Cd²⁺. The SOD activity was lower at 2.20 × 10⁻⁴and 2.75 × 10⁻⁴ g g⁻¹ than that at 1.10 × 10⁻⁴ and 1.65 × 10⁻⁴ g g⁻¹. It appears that SOD had a positive protective effect at low Cd²⁺ concentrations, and that this effect disappeared at high Cd²⁺ concentrations. CAT activity was accelerated to varying degrees at 1.10 × 10⁻⁴ to 2.75 × 10⁻⁴ g g⁻¹ for males and at 1.10 × 10⁻⁴, 2.20 × 10⁻⁴, and 2.75 × 10⁻⁴g g⁻¹ for females. CAT showed a strong detoxification effect with all treatments. GPx activity decreased with increasing Cd²⁺ concentration with all treatments for males and at 2.20 × 10⁻⁴ and 2.65 × 10⁻⁴g g⁻¹ for females. We showed that GPx activity had a weak detoxification function with all treatments for males and at high Cd²⁺ for females. Thus, CAT had a strong detoxification effect, whereas SOD had a medium and GPx had a weak detoxification effect. Among the three enzymes, CAT played an important role in the damaging mechanisms of reactive oxygen species in O. chinensis insects. Alterations of the antioxidant enzyme level under environmental stresses are suggested as indicators of biotic and abiotic stress.     

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.     

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.     

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.