Copper-induced alterations in rat brain depends on route of overload and basal copper levels.

OBJECTIVES: Copper (Cu) is widely used in industry for the manufacture of a vast range of goods including Cu-intrauterine devices (IUDs), electronic products, agrochemicals, and many others. It is also one of the trace elements essential to human health in the right measure and is used as a parenteral supplement in patients unable to ingest food. Elevated Cu levels have been found in the plasma of women using Cu-IUDs and in farmers working with Cu-based pesticides. However, possible alterations due to Cu overload in the brain have been poorly studied. Therefore, the aim of this study was to investigate the effects of Cu administration on rat brain in Cu-sufficient and Cu-deficient animals fed on semi-synthetic diets with different doses of Cu (7 or 35 ppm). METHODS: We aimed to investigate the effects of Cu administration using two routes of administration: oral and intraperitoneal (IP). Male Wistar rats were feeding (one month) a complete (7 ppm) or a deficient (traces) Cu diets subdivided into three categories oral-, intraperitoneal- (or both) supplemented with copper carbonate (7 to 35 ppm). Cu content in plasma, brain zones (cortex and hippocampus), antioxidant enzyme activities, and protease systems involved in programmed cell death were determined. RESULTS: The results show that Cu levels and the concentration of Cu in plasma and brain were dose-dependent and administration route-dependent and demonstrated a prooxidative effect in plasma and brain homogenates. Oxidative stress biomarkers and antioxidative enzyme activity both increased under Cu overload, these effects being more noticeable when Cu was administered IP. Concomitantly, brain lipids from cortex and hippocampus were strongly modified, reflecting Cu-induced prooxidative damage. A significant increase in the activities of calpain (milli- and micro-) and caspase-3 activity also was observed as a function of dose and administration route. CONCLUSION: The findings of this study could be important in evaluating the role of Cu in brain metabolism and neuronal survival.

A Phase I clinical trial of lodenafil carbonate, a new phosphodiesterase Type 5 (PDE5) inhibitor, in healthy male volunteers.

UNLABELLED: Lodenafil carbonate is a new phosphodiesterase Type 5 (PDE5) inhibitor used in treatment of erectile dysfunction. OBJECTIVE: The present study was conducted to evaluate the safety, tolerability, and pharmacokinetics of lodenafil carbonate after administering ascending (1 - 100 mg) single oral doses to healthy male volunteers (n = 33). METHODS: The study was an open label, dose-escalation, Phase I clinical trial involving the administration of single oral doses of lodenafil carbonate. Lodenafil carbonate was administered sequentially, escalating in single doses of 1 mg - 100 mg with a washout period of at least 1 week between each dose. The progression to the next dose was allowed after clinical and laboratory exams, Ambulatory Monitoring of Arterial Pressure (AMAP) without relevant clinical modifications and adverse events without clinical relevancy. Blood samples were collected at pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 14, 16, 20 and 24 h post-dosing. Plasma samples for measurement of lodenafil carbonate and lodenafil were analyzed by liquid chromatography coupled to tandem mass spectrometry. RESULTS: No serious adverse events were observed, and none of the subjects discontinued the study due to intolerance. The AMAP measurements, clinical and laboratory exams and ECG revealed no significant changes even at higher doses. Lodenafil carbonate was not detected in any samples, indicating that it acts as a prodrug. The mean lodenafil pharmacokinetic parameters for tmax and t1/2 were 1.6 ( ± 0.4) h and 3.3 ( ± 1.1) h, respectively. This study demonstrated that lodenafil carbonate was well tolerated and showed a good safety profile in healthy male volunteers.

Fracture strength of incisor crowns after intracoronal bleaching with sodium percarbonate.

OBJECTIVES: To compare the fracture resistance of bovine teeth after intracoronal bleaching with sodium percarbonate (SPC) or sodium perborate (SP) mixed with water or 20% hydrogen peroxide (HP). MATERIALS AND METHODS: Fifty extracted bovine teeth were divided into four experimental groups (G1-G4) and one control (n = 10) after endodontic treatment. Following root canal obturation, a glass ionomer barrier was placed at the cemento-enamel junction. After that, the pulp chambers were filled with: G1 - SP with water; G2 - SP with 20% HP; G3 - SPC with water; and G4 - SPC with 20% HP. No bleaching agent was used in the control group. Coronal access cavities were sealed with glass ionomer and specimens were immersed in artificial saliva. The bleaching agents were replaced after 7 days, and teeth were kept in artificial saliva for an additional 7 days, after which the pastes were removed and the coronal access cavities were restored with glass ionomer. Crowns were subjected to compressive load at a cross head speed of 0.5 mm min(-1) applied at 135° to the long axis of the root by an EMIC DL2000 testing machine, until coronal fracture. Data were statistically analysed by anova and Tukey test. RESULTS: No differences in fracture resistance were observed between the experimental groups (P > 0.05). However, all experimental groups presented lower fracture resistance than the control group (P < 0.05). CONCLUSION: SPC and SP led to equal reduction on fracture resistance of dental crowns, regardless of being mixed with water or 20% HP.

Efficacy and tolerability of lodenafil carbonate for oral therapy of erectile dysfunction: a phase III clinical trial.

INTRODUCTION: This is a phase III, prospective, randomized, double-blind, placebo-controlled clinical trial on lodenafil carbonate (LC), a novel phosphodiesterase 5 inhibitor developed in Brazil. AIM: Expanding information on LC efficacy and safety. MAIN OUTCOME MEASURES: International Index of Erectile Function (IIEF) erectile domain, positive answers to the sexual encounter profile (SEP)-2 and SEP-3 questions and incidence of adverse events (AEs). METHODS: A total of 350 men with erectile dysfunction (ED) of all degrees were randomized to placebo, LC 40 mg or LC 80 mg and followed for 4 weeks. They completed the IIEF and answered the SEP questions 2 and 3 after each intercourse without and with the use of LC. RESULTS: IIEF Erectile Domain scores without and with the use of medication were the following (mean [M] +/- standard deviation [SD]): placebo = 13.9 +/- 5.2 and 14.8 +/- 7.8; LC 40 mg = 13.6 +/- 5.3 and 18.6 +/- 8.0; LC 80 mg = 13.4 +/- 4.9 and 20.6 +/- 7.7 (analysis of variance [ANOVA] P < 0.01). Positive answers to SEP-2 without and with the use of medication were the following (M +/- SD): placebo = 55.3 +/- 43.2% and 52.1 +/- 41.4%; LC 40 mg = 46.4 +/- 44.3% and 63.5 +/- 42.0%; LC 80 mg = 50.2 +/- 40.9% and 80.8 +/- 32.3% (ANOVA P < 0.01). Positive answers to SEP-3 were the following: placebo = 20.2 +/- 32.3% and 29.7 +/- 38.1%; LC 40 mg = 19.6 +/- 34.3% and 50.8 +/- 44.4%; LC 80 mg = 20.8 +/- 33.2% and 66.0 +/- 39.3% (ANOVA P < 0.01). The patients with at least one AE were placebo = 28.7%, LC 40 mg = 40.9%, and LC 80 mg = 49.5%. AEs whose incidence was significantly higher with LC than with placebo included rhinitis, headache, flushing, visual disorder, and dizziness. CONCLUSIONS: LC showed a satisfactory efficacy-safety profile for oral therapy of ED.

Neurotoxicologia clinica: los plaguicidas / Clinical neurotoxicology: pesticides

Los plaguicidas son compuestos quimicos de gran utilidad principalmente en la agriculatura. Su uso incorrecto e indiscriminado ha llevado a cuadros clinicos de neurotoxicidad importantes, en especial de Encefalopatia y Neuropatia Periferica. Se actualizan las diversas manifestaciones clinicas neurologicas en las intoxicaciones por Organofosforados, Organoclorados, Carbonatos, herbicidas como el Paraquat y los Repelentes de insectos