E2 potentializes benzo(a)pyrene-induced hepatic cytochrome P450 enzyme activities in Nile tilapia at high concentrations

In the aquatic environment, biotransformation enzymes are established biomarkers for assessing PAH exposure in fish, but little is known about the effect of 17β-estradiol (E2) on these enzymes during exposure to benzo(a)pyrene (BaP). In this study, Nile tilapia (Oreochromis niloticus) were exposed for 3, 5, and 10 days to BaP (300 μg L(-1)) and E2 (5 μg L(-1)). These substances were applied isolated or mixed. In the mixture experiment, fish were analyzed pre- and postexposure in order to better understand whether preexposure to the hormone masks the responses activated by PAH or vice versa. Phase I enzymes ethoxyresorufin-O-deethylase (EROD), pentoxyresorufin-O-depenthylase (PROD), and benzyloxyresorufin-O-debenzylase (BROD) activities as well as the phase II enzyme glutathione S-transferase (GST) were analyzed. Isolated E2 treatment decreased EROD activity after 3 days, but this enzyme activity returned to control values after 5 and 10 days of exposure. Isolated BaP treatment significantly induced EROD activity after 3 and 5 days, and the activity returned to control levels after ten exposure days. Combined treatment (E2 + Bap) significantly increased EROD activity, both in the pre- and postexposure. This increase was even higher than in the isolated BaP treatment, suggesting a synergism between these two compounds. When E2 and BaP were used singly, they did not change BROD and PROD activities. However, combined treatment (E2 + Bap) significantly increased PROD activity. Isolated BaP treatment increased GST activity after 10 days. However, this response was not observed in the mixture treatment, suggesting that E2 suppressed the GST induction modulated by BaP. The results put together indicated that E2 altered the biotransformation pathway regarding enzymes activated by BaP in Nile tilapia.

Toxicogenetic effects of low concentrations of the pesticides imidacloprid and sulfentrazone individually and in combination in in vitro tests with HepG2 cells and Salmonella typhimurium

The insecticide imidacloprid and the herbicide sulfentrazone are two different classes of pesticides that are used for pest control in sugarcane agriculture. To evaluate the genotoxic potential of low concentrations of these two pesticides alone and in mixture, the comet assay and the micronucleus (MN) test employing fluorescence in situ hybridization (FISH) with a centromeric probe were applied in human hepatoma cell lines (HepG2), in a 24-h assay. Mutagenicity was assessed by Salmonella/microsome assay with TA98 and TA100 strains in the absence and presence of an exogenous metabolizing system (S9). The results showed significant inductions of MN in HepG2 cells by both pesticides, for all the tested concentrations. As evidenced in the comet assay, only the imidacloprid presented significant responses. When the two pesticides were associated, a significant induction of damage was observed in the HepG2 cells by the comet assay, but not by the MN test. Moreover, the MN induced by the mixtures of the pesticides appeared at lower levels than those induced by sulfentrazone and imidacloprid when tested alone. According to the FISH results, the damage induced by imidacloprid in the HepG2 cells resulted from a clastogenic action of this insecticide (76.6% of the MN did not present a centromeric signal). For the herbicide sulfentrazone and for the mixture of the pesticides, a similar frequency of MN with and without the presence of the centromeric signal (herbicide: 52.45% of the MN without centromeric signal and 47.54% of the MN with centromeric signal; mixture: 48.71% of the MN without centromeric signal and 51.42% of the MN with centromeric signal) was verified. Based on these results, it was concluded that each one of the pesticides evaluated interacts with the DNA of HepG2 cells and causes irreparable alterations in the cells. However, the combination of the pesticides showed an antagonistic effect on the cells and the damage induced was milder and not persistent in HepG2 cells. The results obtained by the Ames test did not point out significant results.

Carcass characteristics and meat quality of lambs fed high concentrations of crude glycerin in low-starch diets

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Comparison of droperidol and ondansetron prophylactic effect on subarachnoid morphine-induced pruritus

The prophylactic effect of ondansetron on subarachnoid morphine-induced pruritus is controversial, while evidence suggests that droperidol prevents pruritus. The aim of this study is to compare the effects of droperidol and ondansetron on subarachnoid morphine-induced pruritus. 180 ASA I or II patients scheduled to undergo cesarean sections under subarachnoid anesthesia combined with morphine 0.2mg were randomized to receive, after the child's birth, metoclopramide 10mg (Group I - control), droperidol 2.5mg (Group II) or ondansetron 8mg (Group III). Postoperatively, the patients were assessed for pruritus (absent, mild, moderate or severe) or other side effects by blinded investigators. Patients were also blinded to their group allocation. The tendency to present more severe forms of pruritus was compared between groups. NNT was also determined. Patients assigned to receive droperidol [Proportional odds ratio: 0.45 (95% confidence interval 0.23-0.88)] reported less pruritus than those who received metoclopramide. Ondansetron effect was similar to metoclopramide [Proportional odds ratio: 0.95 (95% confidence interval 0.49-1.83)]. The NNT for droperidol and ondansetron was 4.0 and 14.7, respectively. Ondansetron does not inhibit subarachnoid morphine-induced pruritus.

Changes in malondialdehyde and C-reactive protein concentrations after lifestyle modification are related to different metabolic syndrome-associated pathophysiological processes

Metabolic syndrome (MetS) is often accompanied by pro-oxidative and pro-inflammatory processes. Lifestyle modification (LiSM) may act as primary treatment for these processes. This study aimed to elucidate influencing factors on changes of malondialdehyde (MDA) and C-reactive protein (CRP) concentrations after a LiSM intervention. Sixty subjects (53 yrs, 84% women) clinically approved to attend a 20 weeks LiSM-program were submitted to weekly nutritional counseling and physical activities combining aerobic (3 times/week) and resistance (2 times/week) exercises. Before and after intervention they were assessed for anthropometric, clinical, cardiorespiratory fitness test (CRF) and laboratory markers. Statistical analyses performed were multiple regression analysis and backward stepwise with p<0.05 and R(2) as influence index. LiSM was responsible for elevations in CRF, healthy eating index (HEI), total plasma antioxidant capacity (TAP) and HDL-C along with reductions in waist circumference measures and MetS (47-40%) prevalence. MDA and CRP did not change after LiSM, however, we observed that MDA concentrations were positively influenced (R(2)=0.35) by fasting blood glucose (β=0.64) and HOMA-IR (β=0.58) whereas CRP concentrations were by plasma gamma-glutamyltransferase activity (β=0.54; R(2)=0.29). Pro-oxidant and pro-inflammatory states of MetS can be attenuated after lifestyle modification if glucose metabolism homeostasis were recovered and if liver inflammation were reduced, respectively.

Sedative and cardiopulmonary effects of xylazine alone or in combination with methadone, morphine or tramadol in sheep

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Postoperative pain control in cats: clinical trials with pre-emptive lidocaine epidural co-administered with morphine or methadone

To evaluate the effectiveness of epidural lidocaine in combination with either methadone or morphine for postoperative analgesia in cats undergoing ovariohysterectomy. Under general anesthesia, 24 cats that underwent ovariohysterectomy were randomly allocated into three treatments groups of eight each. Treatment 1 included 2% lidocaine (4.0 mg/kg); treatment 2 included lidocaine and methadone (4.0 mg/kg and 0.3 mg/kg, respectively); and treatment 3 included lidocaine and morphine (4.0 mg/kg and 0.1 mg/kg, respectively). All drugs were injected in a total volume of 0.25 ml/kg via the lumbosacral route in all cats. During the anesthetic and surgical periods, the physiological variables (respiratory and heart rate, arterial blood pressure and rectal temperature) were measured at intervals of time zero, 10 mins, 20 mins, 30 mins, 60 mins and 120 mins. After cats had recovered from anesthesia, a multidimensional composite pain scale was used to assess postoperative analgesia at 2, 4, 8, 12, 18, and 24 h after epidural. The time to first rescue analgesic was significantly (P <0.05) prolonged in cats that received both lidocaine and methadone or lidocaine and morphine treatments compared with those that received the lidocaine treatment. All cats that received lidocaine treatment alone required rescue analgesic within 2 h of epidural injections. All treatments had significant cardiovascular and respiratory changes but they were within acceptable range for healthy animals during the surgical period. The two combinations administered via epidural allowed ovariohysterectomy with sufficient analgesia in cats, and both induced prolonged postoperative analgesia.

Analysis of the genotoxic potential of low concentrations of Malathion on the Allium cepa cells and rat hepatoma tissue culture

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Fluoride concentrations of milk, infant formulae, and soy-based products commercially available in Brazil

To assess the fluoride (F) content in commercially available milk formulae in Brazil and to estimate the F intake in children from this source in the first year of life. Samples of cow's milk (n = 51), infant formulae (n = 15), powdered milk (n = 13), and soy-based products (n = 4) purchased in Araçatuba (Brazil) had their F content measured using an ion-specific electrode, after hexamethyldisiloxane-facilitated diffusion. Powdered milk and infant formulae were reconstituted with deionized water, while ready-to-drink products were analyzed without any dilution. Using average infant body masses and suggested volumes of formula consumption for infants 1-12 months of age, possible F ingestion per body mass was estimated. Data were analyzed by descriptive analysis. Mean F content ranged from 0.02 to 2.52 mg/L in all samples. None of the cow's milk provided F intake higher than 0.07 mg/kg. However, two infant formulae, one powdered milk, and one soy-milk led to a daily F intake above the suggested threshold for fluorosis when reconstituted with deionized water. Assuming reconstitution of products with tap water at 0.7 ppm F, two infant formulae, five powdered milk, and four soymilks led to daily F intake ranging from 0.108 to 0.851 mg/kg. The results suggest that the consumption of some brands of infant formulae, powdered milk, and soy-based milk in the first year of age could increase the risk of dental fluorosis, reinforcing the need for periodic surveillance of the F content of foods and beverages typically consumed by young children.

Influence of crown-to-implant ratio, retention system, restorative material, and occlusal loading on stress concentrations in single short implants

Purpose: The aim of this study was to assess the contributions of some prosthetic parameters such as crown-to-implant (C/I) ratio, retention system, restorative material, and occlusal loading on stress concentrations within a single posterior crown supported by a short implant. Materials and Methods: Computer-aided design software was used to create 32 finite element models of an atrophic posterior partially edentulous mandible with a single external-hexagon implant (5 mm wide × 7 mm long) in the first molar region. Finite element analysis software with a convergence analysis of 5% to mesh refinement was used to evaluate the effects of C/I ratio (1:1; 1.5:1; 2:1, or 2.5:1), prosthetic retention system (cemented or screwed), and restorative material (metal-ceramic or all ceramic). The crowns were loaded with simulated normal or traumatic occlusal forces. The maximum principal stress (σmax) for cortical and cancellous bone and von Mises stress (σvM) for the implant and abutment screw were computed and analyzed. The percent contribution of each variable to the stress concentration was calculated from the sum of squares analysis. Results: Traumatic occlusion and a high C/I ratio increased stress concentrations. The C/I ratio was responsible for 11.45% of the total stress in the cortical bone, whereas occlusal loading contributed 70.92% to the total stress in the implant. The retention system contributed 0.91% of the total stress in the cortical bone. The restorative material was responsible for only 0.09% of the total stress in the cancellous bone. Conclusion: Occlusal loading was the most important stress concentration factor in the finite element model of a single posterior crown supported by a short implant.

Impact of sub-inhibitory concentrations of amoxicillin on helicobacter pylori virulence factors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Seasonal Carbon Dioxide and Oxygen Concentrations in the Dens of Hibernating Mammals (Sciuridae)

This paper reports seasonal changes in respiratory gases in artificial dens of two species of hibernators indigenous to central and northern Alaska: Citellus parryi ablusus(Osgood) and Marmota broweri Hall and Gilmore (Sciuridae).

Assessment of metal and trace element concentrations in the Cananeia estuary, Brazil, by neutron activation and atomic absorption techniques

Twenty six bottom sediment samples were collected from the Cananeia estuary in summer and winter of 2005. Multielemental analysis was carried out by instrumental neutron activation analysis. Total mercury was determined by cold vapor atomic absorption. As, Cr, Hg and Zn concentrations were compared to the Canadian oriented values (TEL and PEL). Sample points 4 and 9 presented higher concentration for most elements and As and Cr exceeded the TEL values. Organic matter (>10%) associated with siltic and clay sediments was observed. Climatic conditions, hydrodynamic and biogeochemical processes promote differences in seasonal concentrations of elements at some points, which contribute to special distributions.

Results from a 15-year study on hydrocarbon concentrations in water and sediment from Admiralty Bay, King George Island, Antarctica

Admiralty Bay on the King George Island hosts the Brazilian, Polish and Peruvian research stations as well as the American and Ecuadorian field stations. Human activities in this region require the use of fossil fuels as an energy source, thereby placing the region at risk of hydrocarbon contamination. Hydrocarbon monitoring was conducted on water and sediment samples from the bay over 15 years. Fluorescence spectroscopy was used for the analysis of total polycyclic aromatic hydrocarbons (PAHs) in seawater samples and gas chromatography with flame ionization and/or mass spectrometric detection was used to analyse individual n-alkanes and PAHs in sediment samples. The results revealed that most sites contaminated by these Compounds are around the Brazilian and Polish research stations due to the intense human activities, mainly during the summer. Moreover, the sediments revealed the presence of hydrocarbons from different sources, suggesting a mixture of the direct input of oil or derivatives and derived from hydrocarbon combustion. A decrease in PAH concentrations occurred following improvement of the sewage treatment facilities at the Brazilian research station, indicating that the contribution from human waste may be significant.

Emtricitabine-Tenofovir Concentrations and Pre-Exposure Prophylaxis Efficacy in Men Who Have Sex with Men

Drug concentrations associated with protection from HIV-1 acquisition have not been determined. We evaluated drug concentrations among men who have sex with men in a substudy of the iPrEx trial (1). In this randomized placebo-controlled trial, daily oral doses of emtricitabine/tenofovir disoproxil fumarate were used as pre-exposure prophylaxis (PrEP) in men who have sex with men. Drug was detected less frequently in blood plasma and in viable cryopreserved peripheral blood mononuclear cells (PBMCs) in HIV-infected cases at the visit when HIV was first discovered compared with controls at the matched time point of the study (8% versus 44%; P < 0.001) and in the 90 days before that visit (11% versus 51%; P < 0.001). An intracellular concentration of the active form of tenofovir, tenofovir-diphosphate (TFV-DP), of 16 fmol per million PBMCs was associated with a 90% reduction in HIV acquisition relative to the placebo arm. Directly observed dosing in a separate study, the STRAND trial, yielded TFV-DP concentrations that, when analyzed according to the iPrEx model, corresponded to an HIV-1 risk reduction of 76% for two doses per week, 96% for four doses per week, and 99% for seven doses per week. Pro-phylactic benefits were observed over a range of doses and drug concentrations, suggesting ways to optimize PrEP regimens for this population.