Therapeutic concentration of morphine reduces oxidative stress in glioma cell line

Morphine is a potent analgesic opioid used extensively for pain treatment. During the last decade, global consumption grew more than 4-fold. However, molecular mechanisms elicited by morphine are not totally understood. Thus, a growing literature indicates that there are additional actions to the analgesic effect. Previous studies about morphine and oxidative stress are controversial and used concentrations outside the range of clinical practice. Therefore, in this study, we hypothesized that a therapeutic concentration of morphine (1 μM) would show a protective effect in a traditional model of oxidative stress. We exposed the C6 glioma cell line to hydrogen peroxide (H₂O₂) and/or morphine for 24 h and evaluated cell viability, lipid peroxidation, and levels of sulfhydryl groups (an indicator of the redox state of the cell). Morphine did not prevent the decrease in cell viability provoked by H₂O₂) but partially prevented lipid peroxidation caused by 0.0025% H₂O₂) (a concentration allowing more than 90% cell viability). Interestingly, this opioid did not alter the increased levels of sulfhydryl groups produced by exposure to 0.0025% H₂O₂), opening the possibility that alternative molecular mechanisms (a direct scavenging activity or the inhibition of NAPDH oxidase) may explain the protective effect registered in the lipid peroxidation assay. Our results demonstrate, for the first time, that morphine in usual analgesic doses may contribute to minimizing oxidative stress in cells of glial origin. This study supports the importance of employing concentrations similar to those used in clinical practice for a better approximation between experimental models and the clinical setting.

Antinociceptive effects of the essential oil of Mentha x villosa leaf and its major constituent piperitenone oxide in mice

Mentha x villosa Huds (Labiatae) is an aromatic herb widely used in folk medicine. Since the essential oil of the herb has many pharmacological activities, including antispasmodic effects, we determined whether the oil and its major constituent, piperitenone oxide (PO), have antinociceptive activity. The essential oil of M. x villosa (EOMV) and PO administered orally at 200 mg/kg (vehicle: 0.1% Tween 80 in water) significantly reduced the writhings induced by acetic acid from control values of 59.5 ± 3.1 s (N = 10) to 31.9 ± 2.8 s (N = 10) and 23.8 ± 3.4 s (N = 10), respectively. When administered at 100 and 200 mg/kg, EOMV reduced the paw licking time for the second phase of the formalin test from the control value of 20.6 ± 2.1 s (N = 13) to 5.3 ± 2.2 s (N = 12) and 2.7 ± 1.2 s (N = 18), respectively. At 100 and 200 mg/kg, PO reduced this second phase to 8.3 ± 2.7 s (N = 12) and 3.0 ± 1.2 s (N = 10), respectively. This effect of EOMV and PO was not reversed by naloxone. EOMV and PO had no significant effect on the first phase of the formalin test. As evaluated by the hot-plate and tail immersion test, EOMV and PO, at doses up to 200 mg/kg, showed no analgesic activity. These results show that EOMV and PO have antinociceptive activity and suggest that this effect is probably an indirect anti-inflammatory effect, which does not involve the central nervous system.

Farmacologia clínica da metadona peridural e intravenosa em cães

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

Uso sustentável da biodiversidade brasileira: prospecção químico-farmacológica em plantas superiores: qualea ssp (vochysiaceae)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Liquens de Mato Grosso do Sul: estudo químico e avaliação da atividade biológica

Pós-graduação em Química - IQ

Efeito da dose única de parecoxibe sobe a função, lesão celular e resposta inflamatória do rim de ratos submetidos à hemorragia aguda

Pós-graduação em Anestesiologia - FMB

Avaliação da atividade hipoglicemiante do extrato bruto de Bauhinia holophylla (Steud.) em camundongos diabéticos induzidos por estreptozotocina

Pós-graduação em Biologia Geral e Aplicada - IBB

Comparação da dor pós-operatória em cães versus gatos após orquiectomia versus ovariohisterectomia

Pós-graduação em Anestesiologia - FMB

Derivados ftalimídicos de compostos antiinflamatórios não-esteróide e/ou moduladores de TNF-(alfa), processo de sua obtenção, composições farmacêuticas contendo os mesmos e seus usos no tratamento de doenças inflamatórias

The present invention relates to phthalimide derivatives of non-steroidal and/or TNF-+- modulating anti-inflammatory compounds as well as the process of obtaining the so-called derivatives, pharmaceutical compositions containing such derivatives and their uses, including use in the treatment of inflammatory diseases, especially those related to chronic inflammatory processes, such as rheumatoid arthritis and intestinal inflammatory diseases (for instance, Chron's disease) and the use of the referred to pharmaceutical compositions as antipyretic, analgesic and platelet antiaggregating medications.

Uso de compostos derivados ftalimidicos e/ou sulfonamídicos no tratamento de doenças em que há a necessidade de diminuição dos níveis do fator TNF-alpha e a necessidade de uma fonte exógena de óxido nítrico, compostos derivados sulfonamídicos. Método de obtenção de um composto derivado sulfonamídico

Preparation and use of phthalimide and/or sulphonamide derivatives with nitric oxide donor properties, having activities in increasing gamma-globin gene expression and anti-inflammatory and analgesic activities, effective in the treatment of hematologic diseases which require reducing the TNF-[alpha] levels and an exogenous source of nitric oxide, such as sickle-cell disease. The functionalized phthalimide derivatives are designed from the prototypes thalidomide and hydroxyurea.

Anestesia local por tumescência com lidocaína em cadelas submetidas a mastectomia

The present study investigated the benefits of tumescent anesthesia with lidocaine in dogs undergoing mastectomy, seeking the patients' comfort and their postoperative recovery. Seven animals, with different weight and breed, who had cancer in the region of mammary chain underwent mastectomy surgery. All animals received the same anesthetic protocol being used as the association between acepromazine and morphine doses of 0.04mg.kg-1 and 0.4mg.kg-1 (IM), respectively. After 15 minutes a catheter was placed in the cephalic vein and induction with propofol 4mg.kg-1 and 0.2mg.kg-1 followed by maintenance with isoflurane anesthesia was done. After instrumentation, we proceeded to the tumescent anesthesia technique with ice-cold solution consisting of Ringer's lactate, lidocaine 2% without epinephrine and adrenaline in a total volume of 15mL.kg-1. The average duration of the procedure was 74±18 minutes. The plasmatic peak of lidocaine was between 30 and 60 minutes after infiltration. The rescue analgesic was performed after approximately seven hours of infiltration. It can be concluded that the tumescent anesthesia with lidocaine should be considered as a constituent of anesthetic and analgesic protocol in dogs undergoing mastectomy surgery providing parameter stability, safety and good quality postoperative recovery.

Efeitos da dipirona, do meloxicam e da associação dipirona e meloxicam sobre a hemostasia em cães conscientes e sobre o controle da dor pós-operatória em cadelas submetidas à ovariosalpingohisterectomia

Pós-graduação em Cirurgia Veterinária - FCAV

Efeitos cardiorrespiratórios da administração subaracnóide de cetamina ou da associação com ifenprodil em equinos anestesiados com sevofluorano

Pós-graduação em Cirurgia Veterinária - FCAV

Effects of Light Activation, Agent Concentration, and Tooth Thickness on Dental Sensitivity After Bleaching

Examining three bleaching systems, this in vivo clinical trial evaluated the relationship among tooth sensitivity, light activation, and agent concentration, and it correlated dental sensitivity with tooth thickness.Materials and Methods: Eighty-seven volunteer patients were included. Inclusion criteria were the presence of anterior teeth without restorations as well as the absence of a previous bleaching experience and absence of non-carious cervical lesions or dental pain. Exclusion criteria included pregnancy or breastfeeding, a maximum of TF3 hypoplasia, tetracycline-fluorosis stains, malpositioned teeth, orthodontic treatment, periodontal disease, and/or analgesic/anti-inflammatory intake. Patients were randomly assigned to three bleaching groups: Group A (n=25) was treated with 15% H2O2 and nitrogenous-titanium-dioxide and was light activated (Lase Peroxide Lite, DMC, SaoCarlos, Sao Paulo, Brazil); Group B (n=27) was treated with 35% H2O2 and was light activated (Lase Peroxide Sensy, DMC); and Group C (n=35) was treated with 35% H2O2 (White Gold Office, Dentsply, 38West Clark Ave., Milford, USA) without light activation. Tooth sensitivity (TS) was self-reported by the patients using the visual analog scale (VAS) at baseline (TSO), immediately after treatment (TSI), and at seven days after treatment (TS7). In 46 patients, tooth thickness was determined by computed tomography. TSO, TSI, and TS7 were compared between the A and B groups to determine the effect of concentration and between the B and C groups to determine the effect of light using analysis of covariance. The correlation between tooth thickness and TSI was determined by Spearman Rho test (SPSS 15).Results: Eighty-seven patients were evaluated at baseline, and 61 were evaluated at seven days. Separated by groups, tooth sensitivity, expressed as VAS value at the time points TS0, TS1, and TS7, respectively, were as follows: Group A: 13.76 +/- 13.53, 24.40 +/- 25.24, and 5.94 +/- 5.5; Group B: 15.07 +/- 18.14, 42.4 +/- 31.78, and 8.68 +/- 17.99; and Group C: 10.80 +/- 14.83, 31.51 +/- 29.34, and 7.24 +/- 9.2. Group A showed significantly lower tooth sensitivity than group B at TSI (p=0.032). No differences were observed in the tooth sensitivities between groups B and C. No correlation was encountered between tooth thickness and tooth sensitivity immediately after treatment (Rho=-0.088,p=0.563). The median tooth thickness was 2.78 +/- 0.21 mm.Conclusions: Increases in the concentration of bleaching agents directly affect tooth sensitivity, and LED/laser activation and tooth thickness are not correlated with tooth sensitivity after dental bleaching.

Pharmacological Evaluation and Preparation of Nonsteroidal Anti-Inflammatory Drugs Containing an N-Acyl Hydrazone Subunit

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