Hypobromous Acid, A Powerful Endogenous Electrophile: Experimental And Theoretical Studies.

Hypobromous acid (HOBr) is an inorganic acid produced by the oxidation of the bromide anion (Br(-)). The blood plasma level of Br(-) is more than 1,000-fold lower than that of chloride anion (Cl(-)). Consequently, the endogenous production of HOBr is also lower compared to hypochlorous acid (HOCl). Nevertheless, there is much evidence of the deleterious effects of HOBr. From these data, we hypothesized that the reactivity of HOBr could be better associated with its electrophilic strength. Our hypothesis was confirmed, since HOBr was significantly more reactive than HOCl when the oxidability of the studied compounds was not relevant. For instance: anisole (HOBr, k2=2.3×10(2)M(-1)s(-1), HOCl non-reactive); dansylglycine (HOBr, k2=7.3×10(6)M(-1)s(-1), HOCl, 5.2×10(2)M(-1)s(-1)); salicylic acid (HOBr, k2=4.0×10(4)M(-1)s(-1), non-reactive); 3-hydroxybenzoic acid (HOBr, k2=5.9×10(4)M(-1)s(-1), HOCl, k2=1.1×10(1)M(-1)s(-1)); uridine (HOBr, k2=1.3×10(3)M(-1)s(-1), HOCl non-reactive). The compounds 4-bromoanisole and 5-bromouridine were identified as the products of the reactions between HOBr and anisole or uridine, respectively, i.e. typical products of electrophilic substitutions. Together, these results show that, rather than an oxidant, HOBr is a powerful electrophilic reactant. This chemical property was theoretically confirmed by measuring the positive Mulliken and ChelpG charges upon bromine and chlorine. In conclusion, the high electrophilicity of HOBr could be behind its well-established deleterious effects. We propose that HOBr is the most powerful endogenous electrophile.

Androgen Therapy Reverses Injuries Caused By Ethanol Consumption In The Prostate: Testosterone As A Possible Target To Ethanol-related Disorders.

Chronic ethanol consumption leads to reproductive damages, since it can act directly in the tissues or indirectly, causing a hormonal imbalance. Prostate is a hormone-dependent gland and, consequently, susceptible to ethanol. The potential of testosterone therapy in the ethanol-related disorders was investigated in the prostate microenvironment. UChB rats aged 90 days were divided into 2 experimental groups (n=20): C: drinking water only and EtOH: drinking 10% (v/v) ethanol at >2 g/kg body weight/day+water. At 150 days old, 10 rats from each group received subcutaneous injections of testosterone cypionate (5 mg/kg body weight) diluted in corn oil every other day for 4 weeks, constituting T and EtOH+T, while the remaining animals received corn oil as vehicle. Animals were euthanized at 180 days old, by decapitation. Blood was collected to obtain hormone concentrations and ventral prostate was dissected and processed for light microscope and molecular analyses. Ventral prostate weight, plasma testosterone and DHT and intraprostatic testosterone concentrations were increased after testosterone treatment. Plasma estradiol level was reduced in the EtOH+T. Inflammatory foci, metaplasia and epithelial atrophy were constantly found in the prostate of EtOH and were not observed after hormonal therapy. No differences were found in the expression of AR, ERβ and DACH-1. Additionally, testosterone treatment down-regulated ERα and increased the e-cadherin and α-actinin immunoreactivities. Testosterone was able to reverse damages caused by ethanol consumption in the prostate microenvironment and becomes a possible target to be investigated to ethanol-related disorders.

Ecotoxicological Effects Of Carbofuran And Oxidised Multiwalled Carbon Nanotubes On The Freshwater Fish Nile Tilapia: Nanotubes Enhance Pesticide Ecotoxicity.

The interactions of carbon nanotubes with pesticides, such as carbofuran, classical contaminants (e.g., pesticides, polyaromatic hydrocarbons, heavy metals, and dyes) and emerging contaminants, including endocrine disruptors, are critical components of the environmental risks of this important class of carbon-based nanomaterials. In this work, we studied the modulation of acute carbofuran toxicity to the freshwater fish Nile tilapia (Oreochromis niloticus) by nitric acid treated multiwalled carbon nanotubes, termed HNO3-MWCNT. Nitric acid oxidation is a common chemical method employed for the purification, functionalisation and aqueous dispersion of carbon nanotubes. HNO3-MWCNT were not toxic to Nile tilapia at concentrations ranging from 0.1 to 3.0 mg/L for exposure times of up to 96 h. After 24, 48, 72 and 96 h, the LC50 values of carbofuran were 4.0, 3.2, 3.0 and 2.4 mg/mL, respectively. To evaluate the influence of carbofuran-nanotube interactions on ecotoxicity, we exposed the Nile tilapia to different concentrations of carbofuran mixed together with a non-toxic concentration of HNO3-MWCNT (1.0 mg/L). After 24, 48, 72, and 96 h of exposure, the LC50 values of carbofuran plus nanotubes were 3.7, 1.6, 0.7 and 0.5 mg/L, respectively. These results demonstrate that HNO3-MWCNT potentiate the acute toxicity of carbofuran, leading to a more than five-fold increase in the LC50 values. Furthermore, the exposure of Nile tilapia to carbofuran plus nanotubes led to decreases in both oxygen consumption and swimming capacity compared to the control. These findings indicate that carbon nanotubes could act as pesticide carriers affecting fish survival, metabolism and behaviour.

Cola beverage consumption delays alveolar bone healing: a histometric study in rats

Epidemiological studies have suggested that cola beverage consumption may affect bone metabolism and increase bone fracture risk. Experimental evidence linking cola beverage consumption to deleterious effects on bone is lacking. Herein, we investigated whether cola beverage consumption from weaning to early puberty delays the rate of reparative bone formation inside the socket of an extracted tooth in rats. Twenty male Wistar rats received cola beverage (cola group) or tap water (control group) ad libitum from the age of 23 days until tooth extraction at 42 days and euthanasia 2 and 3 weeks later. The neoformed bone volume inside the alveolar socket was estimated in semi-serial longitudinal sections using a quantitative differential point-counting method. Histological examination suggested a decrease in the osteogenic process within the tooth sockets of rats from both cola groups, which had thinner and sparser new bone trabeculae. Histometric data confirmed that alveolar bone healing was significantly delayed in cola-fed rats at three weeks after tooth extraction (ANOVA, p = 0.0006, followed by Tukey's test, p < 0.01). Although the results of studies in rats cannot be extrapolated directly to human clinical dentistry, the present study provides evidence that cola beverage consumption negatively affect maxillary bone formation.

Surface and subsurface erosion of primary enamel by acid beverages over time

This study evaluated the influence of a cola-type soft drink and a soy-based orange juice on the surface and subsurface erosion of primary enamel, as a function of the exposure time. Seventy-five primary incisors were divided for microhardness test (n=45) or scanning electron microscopy (SEM) analysis (n=30). The specimens were randomly assigned to 3 groups: 1 - artificial saliva (control); 2 - cola-type soft drink; and 3 - soy-based orange juice. Immersion cycles in the beverages were undertaken under agitation for 5 min, 3 times a day, during 60 days. Surface microhardness was measured at 7, 15, 30, 45 and 60 days. After 60 days, specimens were bisected and subsurface microhardness was measured at 30, 60, 90, 120, 150 and 200 µm from the surface exposed. Data were analyzed by ANOVA and Tukey’s test (a=0.05). Groups 2 and 3 presented similar decrease of surface microhardness. Regarding subsurface microhardness, group 2 presented the lowest values. SEM images revealed that after 60 days the surfaces clearly exhibited structural loss, unlike those immersed in artificial saliva. It may be concluded that erosion of the surfaces exposed to the cola-type soft drink was more accentuated and directly proportional to the exposure time.

Can previous acid etching increase the bond strength of a self-etching primer adhesive to enamel?

Because a greater research effort has been directed to analyzing the adhesive effectiveness of self etch primers to dentin, the aim of this study was to evaluate, by microtensile testing, the bond strength to enamel of a composite resin combined with a conventional adhesive system or with a self-etching primer adhesive, used according to its original prescription or used with previous acid etching. Thirty bovine teeth were divided into 3 groups with 10 teeth each (n= 10). In one of the groups, a self-etching primer (Clearfil SE Bond - Kuraray) was applied in accordance with the manufacturer's instructions and, in the other, it was applied after previous acid etching. In the third group, a conventional adhesive system (Scotchbond Multipurpose Plus - 3M-ESPE) was applied in accordance with the manufacturer's instructions. The results obtained by analysis of variance revealed significant differences between the adhesive systems (F = 22.31). The self-etching primer (Clearfil SE Bond) presented lower enamel bond strength values than the conventional adhesive system (Scotchbond Multipurpose Plus) (m = 39.70 ± 7.07 MPa) both when used according to the original prescription (m = 27.81 ± 2.64 MPa) and with previous acid etching (m = 25.08 ± 4.92 MPa).

The role of γ -aminobutyric acid (Gaba) in somatic embryogenesis of Acca sellowiana Berg. (Myrtaceae)

The γ-aminobutyric acid (Gaba) is a non-protein amino acid found in prokaryotes and eukaryotes. Its role in plant development has not been fully established. This study reports a quantification of the levels of endogenous Gaba, as well as investigation of its role in different stages of somatic embryogenesis in Acca sellowiana Berg. (Myrtaceae). Zygotic embryos were used as explants and they were inoculated into the culture medium contained different concentrations of Gaba (0,2, 4, 6, 8 and 10 µM). The highest concentrations of endogenous Gaba were detected between the third and nine days after inoculation, reaching the value of 12.77 µmol.g-1FW. High frequency of somatic embryogenesis was observed in response to 10 µM Gaba. This treatment also resulted in a large number of normal embryos, and the lowest percentage of formation of fused somatic embryos, phenotypic characteristic of most deformed embryos in all treatments. Also, all treatments promoted the formation of the somatic embryos with positive characteristics of development resumption, which however did not originate the seedlings.

Tensile bond strength and SEM analysis of enamel etched with Er:YAG laser and phosphoric acid: a comparative study In vitro

Er:YAG laser has been studied as a potential tool for restorative dentistry due to its ability to selectively remove oral hard tissue with minimal or no thermal damage to the surrounding tissues. The purpose of this study was to evaluate in vitro the tensile bond strength (TBS) of an adhesive/composite resin system to human enamel surfaces treated with 37% phosphoric acid, Er:YAG laser (lambda=2.94 mum) with a total energy of 16 J (80 mJ/pulse, 2Hz, 200 pulses, 250 ms pulse width), and Er:YAG laser followed by phosphoric acid etching. Analysis of the treated surfaces was performed by scanning electron microscopy (SEM) to assess morphological differences among the groups. TBS means (in MPa) were as follows: Er:YAG laser + acid (11.7 MPa) > acid (8.2 MPa) > Er:YAG laser (6.1 MPa), with the group treated with laser+acid being significantly from the other groups (p=0.0006 and p= 0.00019, respectively). The groups treated with acid alone and laser alone were significantly different from each other (p=0.0003). The SEM analysis revealed morphological changes that corroborate the TBS results, suggesting that the differences in TBS means among the groups are related to the different etching patterns produced by each type of surface treatment. The findings of this study indicate that the association between Er:YAG laser and phosphoric acid can be used as a valuable resource to increase bond strength to laser-prepared enamel.

Effects of prone and supine position on oxygenation and inflammatory mediator in a hydrochloric acid-induced lung dysfunction in rats

PURPOSE: To compare the effectiveness of mechanical ventilation of supine versus prone position in hydrochloric acid (HCl)-induced lung dysfunction. METHODS: Twenty, adult, male, Wistar-EPM-1 rats were anesthetized and randomly grouped (n=5 animals per group) as follows: CS-MV (mechanical ventilation in supine position); CP-MV (mechanical ventilation in prone position); bilateral instillation of HCl and mechanical ventilation in supine position (HCl+S); and bilateral instillation of HCl and mechanical ventilation in prone position (HCl+P). All groups were ventilated for 180 minutes. The blood partial pressures of oxygen and carbon dioxide were measured in the time points 0 (zero; 10 minutes before lung injury for stabilization), and at the end of times acid injury, 60, 120 and 180 minutes of mechanical ventilation. At the end of experiment the animals were euthanized, and bronchoalveolar lavages (BALs) were taken to determine the contents of total proteins, inflammatory mediators, and lungs wet-to-dry ratios. RESULTS: In the HCl+P group the partial pressure of oxygen increased when compared with HCl+S (128.0±2.9 mmHg and 111.0±6.7 mmHg, respectively) within 60 minutes. TNF-α levels in BAL do not differ significantly in the HCl+P group (516.0±5.9 pg/mL), and the HCl+S (513.0±10.6 pg/mL). CONCLUSION: The use of prone position improved oxygenation, but did not reduce TNF-α in BAL upon lung dysfunction induced by HCl.

A fototerapia com diodo emissor de luz (LEDT) aplicada pré-exercício inibe a peroxidação lipídica em atletas após exercício de alta intensidade: um estudo preliminar

Estresse oxidativo é o termo geralmente utilizado para descrever os danos causados pelo desequilíbrio entre pró-oxidantes e antioxidantes no organismo. O aumento no consumo de O2 induzido pelo exercício físico está associado ao aumento das espécies reativas de oxigênio (EROs) sendo estas indutoras do estresse oxidativo. Embora as evidências indiquem um provável efeito inibitório da fototerapia com diodos emissores de luz (LEDT) sobre a produção das EROs, não existem estudos observando tal efeito em atletas. Este estudo preliminar destina-se a verificar os efeitos da aplicação de LEDT previamente ao exercício de alta intensidade sobre a peroxidação lipídica, mensurada através dos níveis sanguíneos de substâncias reativas ao ácido tiobarbitúrico (TBARS). Todos os seis atletas de voleibol do sexo masculino foram submetidos às duas situações: aplicação de LEDT efetiva e aplicação de LEDT placebo. O desempenho no protocolo de exercício adotado não revelou diferença (p > 0,05) entre as duas situações nas variáveis potência pico, potência média e índice de fadiga. Os resultados relacionados com a peroxidação lipídica foram: na situação LEDT efetiva, não foi possível observar diferença estatisticamente significante (p > 0,05) entre os níveis pré e pós-exercício (6,98 ± 0,81 e 7,02 ± 0,47nmol/mL); na situação LEDT (LBP) placebo, houve diferença estatisticamente significante (p = 0,05) entre os valores pré e pós-exercício (7,09 ± 1,28 e 8,43 ± 0,71nmol/mL). Tais resultados demonstram que a aplicação efetiva de LEDT parece ser eficaz no controle da peroxidação lipídica em atletas submetidos a exercício intenso

Modulation of peritoneal macrophage activity by the saturation state of the fatty acid moiety of phosphatidylcholine

To determine the effects of saturated and unsaturated fatty acids in phosphatidylcholine (PC) on macrophage activity, peritoneal lavage cells were cultured in the presence of phosphatidylcholine rich in saturated or unsaturated fatty acids (sat PC and unsat PC, respectively), both used at concentrations of 32 and 64 µM. The treatment of peritoneal macrophages with 64 µM unsat PC increased the production of hydrogen peroxide by 48.3% compared to control (148.3 ± 16.3 vs 100.0 ± 1.8%, N = 15), and both doses of unsat PC increased adhesion capacity by nearly 50%. Moreover, 64 µM unsat PC decreased neutral red uptake by lysosomes by 32.5% compared to the untreated group (67.5 ± 6.8 vs 100.0 ± 5.5%, N = 15), while both 32 and 64 µM unsat PC decreased the production of lipopolysaccharide-elicited nitric oxide by 30.4% (13.5 ± 2.6 vs 19.4 ± 2.5 µM) and 46.4% (10.4 ± 3.1 vs 19.4 ± 2.5 µM), respectively. Unsat PC did not affect anion production in non-stimulated cells or phagocytosis of unopsonized zymosan particles. A different result pattern was obtained for macrophages treated with sat PC. Phorbol 12-miristate 13-acetate-elicited superoxide production and neutral red uptake were decreased by nearly 25% by 32 and 64 µM sat PC, respectively. Sat PC did not affect nitric oxide or hydrogen peroxide production, adhesion capacity or zymosan phagocytosis. Thus, PC modifies macrophage activity, but this effect depends on cell activation state, fatty acid saturation and esterification to PC molecule and PC concentration. Taken together, these results indicate that the fatty acid moiety of PC modulates macrophage activity and, consequently, is likely to affect immune system regulation in vivo.

Synthesis, screening for antiacetylcholinesterase activity and binding mode prediction of a new series of [3-(disubstituted-phosphate)-4,4,4-trifluoro-butyl]-carbamic acid ethyl esters

A series of nine new [3-(disubstituted-phosphate)-4,4,4-trifluoro-butyl]-carbamic acid ethyl esters (phosphate-carbamate compounds) was obtained through the reaction of (4,4,4-trifluoro-3-hydroxybut-1-yl)-carbamic acid ethyl esters with phosphorus oxychloride followed by the addition of alcohols. The products were characterized by ¹H, 13C, 31P, and 19F NMR spectroscopy, GC-MS, and elemental analysis. All the synthesized compounds were screened for acetylcholinesterase (AChE) inhibitory activity using the Ellman method. All compounds containing phosphate and carbamate pharmacophores in their structures showed enzyme inhibition, being the compound bearing the diethoxy phosphate group (2b) the most active compound. Molecular modeling studies were performed to investigate the detailed interactions between AChE active site and small-molecule inhibitor candidates, providing valuable structural insights into AChE inhibition.

Determination of 5-aminosalicylic acid in pharmaceutical formulations by square wave voltammetry at pencil graphite electrodes

An analytical method for the determination of the anti-inflammatory drug 5-aminosalicylic acid (5-ASA) in pharmaceutical formulations using square wave voltammetry at pencil graphite electrodes was developed. After the optimization of the experimental conditions, calibration curves were obtained in the linear concentration range from 9.78 × 10-7 to 7.25 × 10-5 mol L-1 resulting in a limit of detection of 2.12 ± 0.05 x 10-8 mol L-1. Statistical tests showed that the concentrations of 5-ASA in commercial tablets and enemas obtained with the proposed voltammetric method agreed with HPLC values at a 95% confidence level.

Drug consumption among medical students in São Paulo, Brazil: influences of gender and academic year

OBJECTIVE: To analyze alcohol, tobacco and other drug use among medical students. METHOD: Over a five-year period (1996-2001), we evaluated 457 students at the Universidade de São Paulo School of Medicine, located in São Paulo, Brazil. The students participated by filling out an anonymous questionnaire on drug use (lifetime, previous 12 months and previous 30 days). The influence that gender and academic year have on drug use was also analyzed. RESULTS: During the study period, there was an increase in the use of illicit drugs, especially inhalants and amphetamines, among the medical students evaluated. Drug use (except that of marijuana and inhalants) was comparable between the genders, and academic year was an important influencing factor. DISCUSSION: Increased inhalant use was observed among the medical students, especially among males and students in the early undergraduate years. This is suggestive of a specific behavioral pattern among medical students. Our findings corroborate those of previous studies. CONCLUSION: Inhalant use is on the rise among medical students at the Universidade de São Paulo School of Medicine. Because of the negative health effects of illicit drug use, further studies are needed in order to deepen the understanding of this phenomenon and to facilitate the development of preventive measures.