Immunomodulatory Role of CB2 Receptors in Emotional and Cognitive Disorders.

Emotional behavior, memory, and learning have been associated with alterations in the immune system in neuropsychiatric and neurodegenerative diseases. In recent years, several studies pointed out the involvement of the cannabinoid receptor 2 (CB2r) in the immune system and the regulation of inflammation. This receptor is widely distributed in different tissues and organs with higher expression in spleen and immune system cells.

Inflammatory Biomarkers in Addictive Disorders.

Substance use disorders are a group of diseases that are associated with social, professional, and family impairment and that represent a high socio-economic impact on the health systems of countries around the world. These disorders present a very complex diagnosis and treatment regimen due to the lack of suitable biomarkers supporting the correct diagnosis and classification and the difficulty of selecting effective therapies. Over the last few years, several studies have pointed out that these addictive disorders are associated with systemic and central nervous system inflammation, which could play a relevant role in the onset and progression of these diseases.

[Effects of pharmaceutical counseling on the effectiveness of anticoagulation in patients with atrial fibrillation].

Background: Vitamin K antagonists such as acenocoumarol and warfarin are usually indicated for the treatment of Atrial Fibrillation (AF). The Therapeutic Range Time (TRT) is a quality of treatment indicator. Values greater than 65% are associated with significantly lower stroke and bleeding rates.

[Anticoagulant efficacy of different pharmacological presentations of vitamin K antagonists].

Background: Vitamin K antagonist medications (VKA) are essential for the prevention of thromboembolic events, but their effectiveness is influenced by multiple factors, such as the type of medication chosen.

Aim: To evaluate the efficacy in anticoagulant control of the bioequivalent and non-bioequivalent drugs of acenocoumarol compared to the reference drug. To evaluate the efficacy of warfarin bioequivalents available in Chile.

A Pharmacogenetically Guided Acenocoumarol Dosing Algorithm for Chilean Patients: A Discovery Cohort Study.

Background: Vitamin K antagonists (VKA) are used as prophylaxis for thromboembolic events in patients with cardiovascular diseases. The most common VKA are warfarin and acenocoumarol. These drugs have a narrow therapeutic margin and high inter-individual response variability due to clinical and pharmacogenetic variables.

Functionally Significant Coumarin-Related Variant Alleles and Time to Therapeutic Range in Chilean Cardiovascular Patients.

Despite the development of new oral agents over the last decade, vitamin K antagonists (VKAs) remain the most widely used anticoagulants for treating and preventing thromboembolism worldwide. In Chile, the Ministry of Health indicates that acenocoumarol should be used in preference to any other coumarin. Complications of inappropriate dosing are among the most frequently reported adverse events associated with this medication.

[Comparison of point of care capillary international normalized ratio (INR) with INR measured in venous samples].

Background: INR is used to monitor the treatment with vitamin K antagonists. A strategy to reduce waiting times for sampling is to measure INR in a capillary sample using a portable point of care (POC) type coagulometer.

Aim: To evaluate the correlation of CoaguChek Pro II™, Xprecia™ and microINR™ with venous INR measured at the clinical laboratory and their ease of use.

Anticoagulation Management With Coumarinic Drugs in Chilean Patients.

Warfarin and acenocoumarol are used in various cardiovascular disorders to improve the prognosis of patients with thromboembolic disease. However, there is a lack of substantial efficacy and safety data on antithrombotic prophylaxis in several countries, particularly in Latin America. The aim of this study was to provide information about the efficacy of anticoagulants in Chilean patients.

Effects of exposure to pharmaceuticals (diclofenac and carbamazepine) spiked sediments in the midge, Chironomus riparius (Diptera, Chironomidae).

Human and veterinary pharmaceuticals and degradation products are continuously introduced into the environment. To date, there is a lack of information about the effects of pharmaceuticals in spiked toxicity tests with non-target organisms. In this study, we have evaluated the effects of exposure to two common pharmaceuticals in the midge Chironomus riparius in spiked sediment experiments.

[Intravenous thrombolysis for ischemic stroke: Experience in 54 patients].

Background: Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) reduces disability in patients with ischemic stroke. However, its implementation in Chilean public general hospitals has been slow and faces some difficulties.

Aim: To analyze the results of an intravenous thrombolysis protocol implementation in a public general hospital.

Acute ischemic stroke after cardiac catheterization: the protamine low-dose recombinant tissue plasminogen activator pathway.

: Intravenous thrombolysis is the preferred treatment for acute ischemic stroke; however, it remains unestablished in the area of cardiac catheterization. We report three patients with acute ischemic stroke after cardiac catheterization. After reversing the anticoagulant effect of unfractionated heparin with protamine, all of the patients were successfully off-label thrombolyzed with reduced doses of intravenous recombinant tissue plasminogen activator (0.

Influence of temperature on toxicity of single pharmaceuticals and mixtures, in the crustacean A. desmarestii.

Lethal and sublethal responses of the shrimp Atyaephyra desmarestii exposed to three pharmaceutical compounds, Diclofenac (DF), Ibuprofen (IB) and Carbamazepine (CBZ), individually and in mixtures, were evaluated under two temperature scenarios. LC50 (96h) values were obtained individually at 20° and 25°C. At 25°C, mortality in binary and ternary mixtures is higher than at 20°C.

[Effect of VKORC1 and CYP2C9 variants on dosage of oral anticoagulants in Chilean individuals].

Background: The dose of oral anticoagulants (OAC) shows great variability among patients. Pharmacogenetic studies have shown that common variants in genes CYP2C9 (*2 and *3) and VKORC1 (-1639G>A) are associated with lower requirements of OAC.

Aim: To study the association between average maintenance doses of oral anticoagulant therapy required to maintain a stable INR and CYP2C9 and VKORC1 gene variants in Chilean adults.

Preliminary research on 1-(4-bromo-2-nitroimidazol-1-yl)-3-[(18)F]fluoropropan-2-ol as a novel brain hypoxia PET tracer in a rodent model of stroke.

The synthesis of the new radiotracer precursor 4-Br-NITTP and the radiolabeling of the new tracer 1-(4-bromo-2-nitroimidazol-1-yl)-3-[(18)F]fluoropropan-2-ol (4-Br-[(18)F]FMISO) is reported. The cyclic voltammetry behaviour, neuronal cell toxicity, transport through the brain endothelial cell monolayer, in vivo PET imaging and preliminary calculations of the tracer uptake for a rodent model of stroke were studied for the new compound and the results were compared to those obtained with [(18)F]FMISO, the current gold standard PET hypoxia tracer. The new PET brain hypoxia tracer is more easily reduced, has higher CLogP than [(18)F]FMISO and it diffuses more rapidly through brain endothelial cells.

Individual and mixture effects of selected pharmaceuticals on larval development of the estuarine shrimp Palaemon longirostris.

Few ecotoxicological studies incorporate within the experimental design environmental variability and mixture effects when assessing the impact of pollutants on organisms. We have studied the combined effects of selected pharmaceutical compounds and environmental variability in terms of salinity and temperature on survival, development and body mass of larvae of the estuarine shrimp Palaemon longirostris. Drug residues found in coastal waters occur as mixture, and the evaluation of combined effects of simultaneously occurring compounds is indispensable for their environmental risk assessment.

Metal bioavailability in freshwater sediment samples and their influence on ecological status of river basins.

The general aim of this work has been to check the ecological impact of metals on the Ebro river basin. In order to evaluate this, metal behavior considering water, sediment as well as metal bioaccumulation in fish has been studied. Total concentrations of metals, as well as the potentially bioavailable fraction of metals in sediment has also been analyzed by the application of the sequential extraction method (BCR method).

[Management of ischemic strokes derived from intraventricular thrombi: report of two cases].

The origin of 20% of ischemic strokes is a left ventricular thrombus. We report two patients with strokes originating from cardiac thrombi, treated in two different ways. A 42-year-old diabetic man admitted with a left parietal and occipital stroke.

Assessment of sediment ecotoxicological status as a complementary tool for the evaluation of surface water quality: the Ebro river basin case study.

According to the European Water Framework Directive (WFD), assessment of surface water status is based on ecological and chemical status that is not always in coherence. In these situations, ecotoxicity tests could help to obtain a better characterization of the ecosystems. The general aim of this work is to design a methodology to study the ecotoxicological status of freshwater systems.

Dequalinium induces cytotoxicity in human leukemia NB4 cells by downregulation of Raf/MEK/ERK and PI3K/Akt signaling pathways and potentiation of specific inhibitors of these pathways.

Delocalized lipophilic cation dequalinium (DQA) selectively accumulates in mitochondria and displays anticancer activity in different malignancies. Our previous studies indicate a DQA-induced cytotoxicity in human acute promyelocytic leukemia NB4 cells by early disturbance in mitochondrial function and oxidative stress. This study shows the ability of DQA to downregulate Raf/MEK/ERK1/2 and PI3K/Akt signaling pathways in NB4 cells which leads to cell death by apoptosis and/or necrosis.

Is Atyaephyra desmarestii a useful candidate for lethal and sub-lethal toxicity tests on pharmaceutical compounds?

Single and mixture toxicity tests on three pharmaceutical compounds, Diclofenac (DF), Ibuprofen (IB) and Carbamazepine (CBZ), were carried out with the freshwater shrimp Atyaephyra desmarestii. Lethal and sublethal responses were analyzed for single compounds. Lethal concentrations (LC50) obtained for each individual compound, after 96 h of exposure, were 6.

Dequalinium induces human leukemia cell death by affecting the redox balance.

Dequalinium, an amphiphilic quinolinium derivative, selectively accumulates in mitochondria and displays anticancer activity in cells from different malignancies. Previous studies indicate a differential DQA-induced cytotoxicity in NB4 and K562 human leukemia cells as a consequence of an early disturbance in mitochondrial function. Results in this paper show that DQA induces a concentration-dependent oxidative stress by decreasing GSH level and increasing ROS in a cell type specific way.

Dequalinium induces cell death in human leukemia cells by early mitochondrial alterations which enhance ROS production.

Dequalinium (DQA) has been proposed as a selective antitumoral agent due to its preferential accumulation in mitochondria of cancer cells. Our aim was a better understanding of DQA cytotoxicity. DQA-induced NB4 and K562 cell alterations are initiated within the first 30 min of treatment at a high DQA concentration with a mitochondrial membrane depolarization.

Effects of the antitumoural dequalinium on NB4 and K562 human leukemia cell lines. Mitochondrial implication in cell death.

Dequalinium (DQA) is a delocalized lipophylic cation that selectively targets the mitochondria of carcinoma cells. However, the underlying mechanisms of DQA action are not yet well understood. We have studied the effects of DQA on two different leukemia cell lines: NB4, derived from acute promyelocytic leukemia, and K562, derived from chronic myeloid leukemia.

Angiotensin inhibition reduces glomerular damage and renal chemokine expression in MRL/lpr mice.

Beneficial effects of angiotensin II inhibition during inflammatory renal disease may involve both hemodynamic and nonhemodynamic mechanisms. To analyze whether angiotensin II inhibition has protective effects on lupus-like, autoimmune-mediated renal damage in MRL/lpr mice, four groups of mice were treated orally for 6 weeks with: 1) vehicle, 2) enalapril (3.0 mg/kg per day), 3) candesartan cilexetil (5.