Effects of combined physical exercise on plasma lipid variables, paraoxonase 1 activity, and inflammation parameters in adults with obesity: a randomized clinical trial.

OBJECTIVE: We aimed to investigate whether combined physical exercise may affect plasma lipid variables, paraoxonase 1 (PON1) activity, and inflammation parameters in adults with obesity. METHODS: Thirty-six participants were recruited to complete the study protocol. The mean age was 37 ± 1 years, and the baseline body mass index was 33.0 ± 0.4 kg/m2. Participants were allocated to the control group (CG) and the exercise group (EG). The EG performed three weekly sessions of combined physical exercise for 16 weeks. Plasma lipid variables, PON1 activity, and inflammatory profile were determined before and after intervention. RESULTS: Total cholesterol levels decreased in both groups, without intergroup difference (time p = 0.001). Non-high-density lipoprotein cholesterol (HDL-C) levels decreased in both groups (time p = 0.001); however, they were lower in the EG than in the CG (p = 0.038). The EG had increased HDL-C levels, but the CG had decreased HDL-C levels (time*group p = 0.011). PON1 activity was reduced in both groups (time, p = 0.001). The Castelli risk Index I and II reduced in the EG and increased in the CG (time*group, p = 0.008 and p = 0.011, respectively). The inflammatory markers were not modified. CONCLUSION: Adults with obesity may benefit from regular practice of combined physical exercise training in many metabolic aspects that are related to protection against the development of cardiovascular disease.

Different outcomes of a cardiac rehabilitation programme in functional parameters among myocardial infarction survivors according to ejection fraction.

INTRODUCTION: Exercise-based cardiac rehabilitation (EBCR) is part of the management of patients who have suffered an acute myocardial infarction (AMI). Patients with a reduced ejection fraction (EF) comprise a higher-risk subgroup and are referred less often for these programmes. This study aimed at assessing the impact of the baseline EF on the functional benefits, as assessed by peak oxygen uptake (pVO2) and exercise duration, of an EBCR programme in AMI survivors. METHODS: Observational, retrospective cohort study including all patients admitted to a tertiary centre due to an AMI who completed a phase II EBCR programme after discharge, between November 2012 and April 2017. Functional parameters were assessed by a symptom-limited cardiopulmonary exercise test. RESULTS: A total of 379 patients were included [40.9% with reduced EF (<50%) at discharge]. After the programme, pVO2 and exercise duration increased significantly (p < 0.001). Patients with a reduced EF had a lower pVO2 and completed a shorter duration of exercise at the beginning and end of the programme. This group presented a higher increase in pVO2 (p = 0.001) and exercise duration (p = 0.007). This was maintained after adjusting for age, gender, history of coronary artery disease, number of sessions, Killip classification, arterial hypertension, dyslipidaemia, diabetes mellitus, smoking status and baseline pVO2. CONCLUSION: A phase II EBCR programme was associated with significant improvements in pVO2 and exercise duration among AMI survivors, irrespective of baseline EF classification. Those with a reduced baseline EF derived an even greater improvement, highlighting the importance of EBCR in this subgroup of patients.

Neonatal hyperthyroidism on rat heart: interrelation with nitric oxide and sex.

PURPOSE: To clarify the mechanism mediating the effect of hyperthyroidism on cardiac function during the second month of life in rats. METHODS: Male and female Sprague-Dawley rats were assigned to a control or to a triiodothyronine (T3)-treated group. Treatment of each group was started on the third day after birth. Control rats (Eut) received 0.9 NaCl [0.1 ml/100 g body weight (BW)] every second day during 60 days and T3-treated rats (Hyper) received subcutaneous (SC) T3 injections every second day during 60 days. RESULTS: Hyperthyroidism decreased left ventricle volume only in male rats. Female euthyroid rats presented higher atrial nitric oxide synthase (NOS) activity than male rats and hormonal treatment decreased this enzyme's activity in both sexes. Euthyroid male and female rats had similar atrial NOS protein levels, but females had higher caveolin (cav) 3 protein levels. T3 treatment increased this protein only in males. Female rats had lower ventricular NOS activity than male rats; hyperthyroidism increased NOS activity in both sexes but this effect was associated with lower cav 3 protein levels. Hyperthyroidism did not change cav 1 protein levels in both male and female rats. CONCLUSIONS: The results of this study demonstrating clinically relevant sex-related differences in the pathophysiology of the hyperthyroid heart have raised new questions regarding the mechanisms responsible for the observed differences. This study suggests that sex-related intrinsic factors such as nitric oxide may modulate the response to hyperthyroidism that leads to cardiovascular dysfunction.

Antioxidant activity of hyaluronic acid investigated by means of chemiluminescence of equine neutrophil bursts and electron paramagnetic resonance spectroscopy.

Activated neutrophils (PMNs), the ROS/RNS released by PMNs and the derived inflammatory processes are involved in the pathogenesis and progression of human inflammatory airway diseases. Similar diseases are also present in horses which suffer from recurrent airway obstruction (RAO), exercise-induced pulmonary haemorrhage (EIPH) and inflammatory airway diseases (IAD). Hyaluronic acid (HA) plays numerous roles in modulating inflammatory processes. The aim of this study was to examine whether a preparation of HA (MW 900 000 Da) interferes with ROS/RNS during the course of equine PMN respiratory bursts, and to establish the lowest concentration at which it still has antioxidant activity by means of luminol-amplified chemiluminescence (LACL). Electron paramagnetic resonance (EPR) spectroscopy was also used to investigate the direct antiradical activity of HA. The hydroxyl radical was significantly scavenged in a concentration-dependent manner at HA concentrations ranging from 2.5 to 0.16 mg/mL. Superoxide anion, Tempol radical and the ABTS(•+) were significantly inhibited at concentrations ranging from 2.5 to 0.62 mg/mL. The LACL of stimulated equine neutrophils showed that HA induced a statistically significant concentration-effect reduction from 5 mg/mL to 1.25 mg/mL. These findings were confirmed also when l-Arg was added to investigate the inhibition of the resulting peroxynitrite anion. Our findings indicate that, in addition to the human use, HA can also be used to antagonize the oxidative stress generated by free radicals in horses peripheral blood mononuclear cells (PBMCs). In order to achieve therapeutic concentrations, a direct aerosol administration to horses with horse respiratory diseases can be considered, as this route of application is also recommended in human medicine.

In-a-dish: induced pluripotent stem cells as a novel model for human diseases.

Human pluripotent stem cells bring promise in regenerative medicine due to their self-renewing ability and the potential to become any cell type in the body. Moreover, pluripotent stem cells can produce specialized cell types that are affected in certain diseases, generating a new way to study cellular and molecular mechanisms involved in the disease pathology under the controlled conditions of a scientific laboratory. Thus, induced pluripotent stem cells (iPSC) are already being used to gain insights into the biological mechanisms of several human disorders. Here we review the use of iPSC as a novel tool for disease modeling in the lab.

Combined effects of Limonene and Ivermectin on P-glycoprotein-9 gene expression of lambs Infected with Haemonchus contortus.

Although ivermectin (IVM) has a wide spectrum and long half-life, its frequent use as an anthelmintic for the last 42 years led to its worldwide tolerance by Haemonchus contortus. We evaluated the combination of limonene (LIM), a P-glycoprotein (Pgp) modulator, with IVM in lambs infected with a multidrug-resistant H. contortus. Twenty-four male Dorper lambs were artificially infected with two doses (seven days apart) of 8000 infective larvae of a multidrug-resistant isolate of H. contortus. The infection was patent 25 days later. Fifteen days before treatment with IVM (DAY -15), animals were divided into 4 groups: Infected-untreated control (CTL), IVM, LIM, and LIM+IVM. From DAY -15 to DAY + 14, groups LIM and LIM+IVM received 200 mg/kg of body weight/day of LIM via oral. On DAY 0, a single dose of IVM at 200 µg/kg of body weight was administered orally to groups IVM and LIM+IVM. On DAY + 7 and DAY + 14, fecal egg counts (FEC) were performed and on DAY + 14 animals were euthanized for total worm count (TWC), worm length, fecundity of females, and Pgp-9 gene expression. On DAY + 7, group LIM+IVM had 96.29% efficacy based on Fecal Egg Count Reduction TEST (FECRT) and a highly significant reduction in FEC (P = 0.0005) when compared to CTL. On DAY + 14, the efficacy of LIM+IVM was 82.87% on FECRT, although no differences were found among groups for FEC, TWC, worm length, or Pgp-9 gene expression. Female worms from the CTL group had higher egg counts in their uterus when compared to LIM. No differences were found for hematological or biochemical parameters, body weight, or weight gain among groups. Thus, LIM given daily at 200 mg/kg was safe for animals and, when combined with IVM, decreased egg shedding and could reduce pasture contamination, although it was unable to kill multidrug-resistant H. contortus.

Cognitive function in patients with chronic pain treated with opioids: characteristics and associated factors.

BACKGROUND: The paucity of studies regarding cognitive function in patients with chronic pain, and growing evidence regarding the cognitive effects of pain and opioids on cognitive function prompted us to assess cognition via neuropsychological measurement in patients with chronic non-cancer pain treated with opioids. METHODS: In this cross-sectional study, 49 patients were assessed by Continuous Reaction Time, Finger Tapping, Digit Span, Trail Making Test-B and Mini-mental State Examination tests. Linear regressions were applied. RESULTS: Patients scored poorly in the Trail Making Test-B (mean = 107.6 s, SD = 61.0, cut-off = 91 s); and adequately on all other tests. Several associations among independent variables and cognitive tests were observed. In the multiple regression analyses, the variables associated with statistically significant poor cognitive performance were female sex, higher age, lower annual income, lower schooling, anxiety, depression, tiredness, lower opioid dose, and more than 5 h of sleep the night before assessment (P < 0.05). CONCLUSIONS: Patients with chronic pain may have cognitive dysfunction related to some reversible factors, which can be optimized by therapeutic interventions.

Characterisation of the antioxidant effects of Aesculus hippocastanum L. bark extract on the basis of radical scavenging activity, the chemiluminescence of human neutrophil bursts and lipoperoxidation assay.

OBJECTIVES: Oxidative stress is increasingly recognised as a pivotal factor that plays a number of roles in the inflammatory response to environmental signals. It has been claimed that Aesculus hippocastanum extracts have antioxidant and anti-inflammatory activity, but these claims are mainly based on the results of chemical reactions and folk-medicine. MATERIALS AND METHODS: The aim of this study was to examine whether a bark extract of Aesculus hippocastanum interferes with reactive oxygen/nitrogen species (ROS/RNS) during the course of human neutrophil respiratory bursts, and to establish the lowest concentration at which it still has antioxidant activity by means of luminol amplified chemiluminescence (LACL). We also studied its ability to counteract lipid peroxidation (LPO) in human cells. Before investigating its antioxidant effects on human cells, we analysed its scavenging activity against ABTS*+, hydroxyl radical, superoxide anion, and Fremy's salt (those last three by means of electron paramagnetic resonance (EPR) spectrometry). RESULTS: The extract of Aesculus hippocastanum exerted its anti-ROS/RNS activity in a concentration-dependent manner with significant effects being observed for even very low concentrations: 10 microg/ml without L-Arg, and 5 microg/ml when L-Arg was added to the fMLP test. The LPO assay confirmed these results, which were paralleled by the EPR study. CONCLUSIONS: These findings are interesting for improving the antioxidant network and restoring redox balance in human cells, and extend the possibility of using plant-derived molecules to antagonise the oxidative stress generated in living organisms when the balance is in favour of free radicals as a result of the depletion of cell antioxidants.

Factors affecting executive function performance of Brazilian elderly in the Stroop test.

Aging is related to a decrease in physiological abilities, especially cognitive functions. To unravel further evidence of age-related cognitive decline, we analyzed which physical and functional variables are predictors of cognitive performance in a sample of 498 Brazilian elderly (67.26% women). To do so, we used the Stroop test as a tool to evaluate executive functions and the General functional fitness index (GFFI) to evaluate the functional fitness of the participants. A linear regression analysis revealed that female sex (ß=-0.097; t=-2.286; P=0.023), younger age (ß=0.205; t=4.606; P<0.0001), more years of education (ß=-0.280; t=-6.358; P<0.0001), and higher GFFI (ß=-0.101; t=-2.347; P<0.02) were predictors of better cognitive performance. Body mass index (kg/m2) and nutritional status (underweight, eutrophic, overweight, or obese) were not predictors of cognitive performance. Interestingly, among the GFFI tasks, muscle strength influenced the test execution time, both in upper and lower limbs (elbow flexion: ß=-0.201; t=-4.672; P<0.0001; sit-to-stand: ß=-0.125; t=-2.580; P<0.01). Our findings showed that: 1) women performed the Stroop test faster than men; 2) the older the person, the lower was the cognitive performance; 3) the higher the education, the better the test execution time; and 4) higher scores in the GFFI were associated with a better performance in the Stroop test. Therefore, gender, age, education, and functional fitness and capacity were predictors of cognitive performance in the elderly.

PERCUTANEOUS TRANSAXILLARY TRANSCATHETER AORTIC VALVE IMPLANTATION.

The transaxillary (TAX) approach for transcatheter aortic valve implantation (TAVI) results in comparable short and long-term clinical results compared to the transfemoral (TF) approach. However, adequate closure of the axillary artery is the most critical issue when performing the percutaneous approach. Compared to surgical transaxillary approach, the percutaneous approach was used only in selected cases due to this closure limitation. In the present paper, we aim to demonstrate the feasibility of implanting the CoreValve Evolut Pro transcatheter heart valve via percutaneous transaxillary approach and make a literature review of procedure particularities and outcome. We describe the case of a patient with severe aortic stenosis in the presence of small calibre and severely calcified femoral arteries. A CoreValve Evolut Pro 26 was successfully implanted percutaneously through the left axillary artery. Percutaneous transaxillary transcatheter aortic valve implantation is a feasible and safe alternative in patients who have suboptimal iliofemoral vessels.

Corpses against science death: new Italian law titled 'Rules relating to the directives of one's body and tissues post-mortem for study, training, and scientific research purposes'.

The new Italian Law no. 10 of 2020, titled 'Rules relating to the directives of one's body and tissues post-mortem for study, training, and scientific research purposes' (10 February, 2020), has opened the doors to a new and clearer regimentation on body donation to science, according to the procedure already introduced by Law no. 219/2017 on the 'Rules relating to informed consent and advance directives of treatment'. The authors exposed some concerning regarding the application of the law, such as donation mistrust, also linked to our cultural heritage; the incomplete protection of minor and incompetent people; the complexity of an adequate information, which could undermine the informed consent; and finally, the fees overload for research institutes, with already exiguous budgets. Next, the authors analysed some positive aspects of the law and in primis the central role of corpses in scientifical knowledge and medical training. Moreover, a simple mechanism based on a conscious and pre-stated consent, registered in a database that follows European data protection Regulation, is discussed. Further, the procedure of the restitution of the bodies to their families, which represents a way to guarantee the relatives' commemoration, is also elucidated. In conclusion, the authors proposed a format of informed consent, to try a direct application of the law, thereby fastening the process of standardisation and centralisation of all the living wills. The authors optimistically investigated the opportunities offered by the law and encouraged a conscientious participation by citizens.

Visual analysis of vaginal cell binding and retention of a gynecological douche.

AIM: Gynecological douches may contain various molecules that need to cover and be retained by cutaneous and mucosal cells if they are to act efficaciously in treating local conditions. The aim of this study was to investigate the possibility of directly visualising the ability of a commercial medical gynecological douche to bind to, and be retained by human vaginal cells. METHODS: The commercial gynecological douche under study was "Saugella Attiva douche", bought at local chemist. The vaginal epithelial cells were obtained from healthy, non-pregnant, regularly menstruating women aged 24-52 years. The cells were obtained from the mucosal surface of the mid-vaginal wall by means of gentle scraping with a sterile spatula. Ferric oxide particles and Escherichia coli were used as inorganic and organic markers in order to visualize the adherence of the transparent thin film of a gynecological douche to human vaginal cells by means of Nomarski interference contrast microscopy and scanning electron microscopy. RESULTS: Both markers made it possible to clearly visualize the binding and retention of the transparent thin layer of the douche also at the dilution 1:2 and 1:4. CONCLUSIONS: The fact that the douche can be locally retained is useful because its formulation contains thymol and eugenol, which are known to have antibacterial, antifungal and antioxidant effects but need a period of contact before they act fully.

Cardiac surgery in infective endocarditis and predictors of in-hospital mortality. / Cirurgia cardíaca na endocardite infeciosa e preditores da mortalidade intra­hospitalar.

INTRODUCTION: Infective endocarditis (IE) is a serious disease with significant in-hospital mortality (15-30%) despite advances in medical and surgical therapy. AIMS: To perform a clinical characterization of patients undergoing cardiac surgery for IE and to identify factors that predict in-hospital mortality. METHODS: We retrospectively analyzed 145 patients with IE admitted between January 2006 and October 2017. RESULTS: The median age was 72 years. IE was acquired mainly in the community (69%), and involved the native aortic valve in 54% of patients, biological prosthetic valves in 22.1% and mechanical valves in 10.3%. Staphylococcus spp. (31.0%) were the most frequent etiological agents. Cardiac surgery was emergent in 29 patients, urgent in 108, and elective in eight. The main indications were heart failure (57.9%), large vegetations (20%), systemic embolism (17.2%) and valve dysfunction (15.2%). Overall, biological valves were implanted in 62.1% of patients and mechanical valves in 37.2%. A total of 19 patients (13.1%) died. Predictors of mortality were preoperative atrial fibrillation and lower left ventricular ejection fraction, postoperative severe valve regurgitation associated with cardiogenic shock, sepsis, septic shock associated with cardiogenic shock, cardiac tamponade, need for renal replacement therapy and, although without statistical significance, emergent surgery. CONCLUSIONS: There is a need for better indicators to enable early identification of surgical candidates for IE, implementation of a heart team, and better surgical strategies, including more rapid intervention, more specific postoperative care, and optimal antibiotic therapy.

Identification of three distinguishable phenotypes in golden retriever muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a human disease characterized by progressive and irreversible skeletal muscle degeneration caused by mutations in genes coding for important muscle proteins. Unfortunately, there is no efficient treatment for this disease; it causes progressive loss of motor and muscular ability until death. The canine model (golden retriever muscular dystrophy) is similar to DMD, showing similar clinical signs. Fifteen dogs were followed from birth and closely observed for clinical signs. Dogs had their disease status confirmed by polymerase chain reaction analysis and genotyping. Clinical observations of musculoskeletal, morphological, gastrointestinal, respiratory, cardiovascular, and renal features allowed us to identify three distinguishable phenotypes in dystrophic dogs: mild (grade I), moderate (grade II) and severe (grade III). These three groups showed no difference in dystrophic alterations of muscle morphology and creatine kinase levels. This information will be useful for therapeutic trials, because DMD also shows significant, inter- and intra-familiar clinical variability. Additionally, being aware of phenotypic differences in this animal model is essential for correct interpretation and understanding of results obtained in pre-clinical trials.

[Clinico-electroencephalographic variants in pharmacoresistant mesial temporal lobe epilepsy]. / Variantes clinicoelectroencefalograficas en la epilepsia del lobulo temporal mesial farmacorresistente.

INTRODUCTION: Focal epilepsy secondary to mesial temporal sclerosis (MTS) is one of the main causes of refractory epilepsy. It is typically associated with frontotemporal discharges in the electroencephalogram (EEG), a characteristic image in the magnetic resonance scan and a probability of post-operative remission above 70%. AIMS: To identify different patterns of ictal propagation in surface EEG recordings in patients with refractory epilepsy and MTS, and to analyse their relation with the post-operative outcome. PATIENTS AND METHODS: We conducted a retrospective review of the medical records of patients with refractory epilepsy secondary to MTS evaluated in the Epilepsy Surgery Programme of the Hospital de Clinicas, Montevideo (n = 30). The propagation of ictal rhythms was analysed in time windows of three seconds, and propagation maps were produced for each seizure. RESULTS: Six patterns were identified: ipsilateral temporal (type 1; 37%), bilateral frontotemporal with (type 2A; 22%) or without (type 2B; 17%) extension to suprasylvian regions, alternating temporal (type 3; 13%), unilateral suprasylvian (type 4; 7%) and bilateral at onset (type 5; 3%). The type 1 pattern was associated with classic clinical features and a favourable post-operative outcome. The clinical variants were associated with extratemporal EEG propagation. Patients with reflex seizures continued with post-operative seizures. Overall, no unambiguous relation was found between the ictal EEG pattern and the post-operative outcome. CONCLUSIONS: The ictal EEG pattern does not allow for a surgical prognosis in patients with epilepsy secondary to MTS. The history of reflex seizures in these patients may be a red flag suggesting a less favourable surgical outcome.

TITLE: Variantes clinicoelectroencefalograficas en la epilepsia del lobulo temporal mesial farmacorresistente.Introduccion. La epilepsia focal secundaria a esclerosis temporal mesial (ETM) constituye una de las principales causas de epilepsia refractaria al tratamiento farmacologico. Tipicamente asocia descargas frontotemporales en el electroencefalograma (EEG), imagen caracteristica en la resonancia magnetica y probabilidad de remision posquirurgica mayor del 70%. Objetivos. Identificar diferentes patrones de propagacion ictal en los registros electroencefalograficos de superficie en pacientes con epilepsia farmacorresistente y ETM, y analizar su relacion con la evolucion postoperatoria. Pacientes y metodos. Se revisaron retrospectivamente los registros de pacientes con epilepsia refractaria secundaria a ETM evaluados en el Programa de Cirugia de Epilepsia del Hospital de Clinicas, Montevideo (n = 30). La propagacion de ritmos ictales se analizo en ventanas temporales de tres segundos, y se elaboraron mapas de propagacion para cada crisis. Resultados. Se identificaron seis patrones: temporal ipsilateral (tipo 1; 37%), frontotemporal bilateral con (tipo 2A; 22%) o sin (tipo 2B; 17%) extension a regiones suprasilvianas, temporal alternante (tipo 3; 13%), suprasilviano unilateral (tipo 4; 7%) y bilateral de inicio (tipo 5; 3%). El patron de tipo 1 asocio un cuadro clinico clasico y buena evolucion posquirurgica. Las variantes clinicas se asociaron a propagacion EEG extratemporal. Los pacientes con crisis reflejas persistieron con crisis postoperatorias. En su conjunto, no se hallo una relacion univoca entre el patron EEG ictal y la evolucion postoperatoria. Conclusiones. El patron EEG ictal no permite predecir el pronostico quirurgico en pacientes con epilepsia secundaria a ETM. La historia de crisis reflejas en estos pacientes puede constituir una 'bandera roja' y sugerir un peor pronostico quirurgico.

The Impact of the Right Coronary Artery Geometric Parameters on Hemodynamic Performance.

PURPOSE: Coronary artery geometry can have a significant impact in the hemodynamic behavior of coronary blood flow, influencing atherosclerotic plaque formation. The present work focuses on, through a statistical study, the connection between several geometric parameters of the right coronary artery-ostium cross-sectional area, angles between the common trunk and the side-branches, tortuosity, curvature and cross-sectional area in each side-branch-and their influence on hemodynamic descriptors. Parameters such as low wall shear stress and local disturbed flow, which are associated with atherosclerosis formation, were analysed. METHODS: Computed tomography images of ten healthy individuals were selected to reconstruct in vivo three-dimensional models of right coronary arteries. Blood flow was simulated through a compliant model with realistic boundary conditions. Calculated hemodynamic descriptors values were correlated with the geometric parameters using the Pearson correlation coefficient (r) and the p value. RESULTS: The strongest correlations were found in the middle and distal segments of the right coronary artery. A decrease in the ostium area promotes a decrease in the WSS magnitude from the proximal to the distal segment (r = 0.82). Very strong correlations (r > 0.90) were achieved between geometric parameters (cross-sectional area, angle, tortuosity) of the right-ventricular branch and the wall shear stress magnitude in the middle and distal segments. CONCLUSIONS: Low values of tortuosity, smaller cross-sectional area and higher angle of the right-ventricular branch leads to a hemodynamic behavior more propitious to atherosclerosis formation, within the study cases. The right-ventricular branch seems to have the highest influence in the hemodynamic behavior of the right coronary artery.

Identification of Staphylococcus epidermidis with transferrable mupirocin resistance from canine skin.

Resistance to mupirocin was analysed in Staphylococcus spp. isolated from healthy dogs (n=21) and dogs with pyoderma (n=47) or otitis externa (n=52). Isolates were identified to species level by MALDI-TOF and PCR-RFLP of the groEL gene. One isolate of Staphylococcus epidermidis from the skin of a healthy dog, which harboured a plasmid carrying the mupA gene, was resistant to mupirocin.

Adrenergic receptor ß3 is involved in the memory consolidation process in mice.

Attention and emotion have a positive impact on memory formation, which is related to the activation of the noradrenergic system in the brain. The hippocampus and amygdala are fundamental structures in memory acquisition, which is modulated by noradrenaline through the noradrenergic receptors. Pharmacological studies suggest that memory acquisition depends on the action of both the ß3 (ß3-AR) and ß2 (ß2-AR) receptor subtypes. However, the use of animal models with specific knockout for the ß3-AR receptor only (ß3-ARKO) allows researchers to more accurately assess its role in memory formation processes. In the present study, we evaluated short- and long-term memory acquisition capacity in ß3-ARKO mice and wild-type mice at approximately 60 days of age. The animals were submitted to the open field test, the elevated plus maze, object recognition, and social preference. The results showed that the absence of the ß3-AR receptor caused no impairment in locomotion and did not cause anxious behavior, but it caused significant impairment of short- and long-term memory compared to wild-type animals. We also evaluated the expression of genes involved in memory consolidation. The mRNA levels for GLUT3, a glucose transporter expressed in the central nervous system, were significantly reduced in the amygdala, but not in the hippocampus of the ß3-ARKO animals. Our results showed that ß3-AR was involved in the process of acquisition of declarative memory, and its action may be due to the facilitation of glucose absorption in the amygdala.

Eugenol and thymol, alone or in combination, induce morphological alterations in the envelope of Candida albicans.

The envelope of Candida albicans, with its outermost array of macromolecules protruding towards the environment, is pivotal to the expression of major virulence factors such as adhesiveness, and the morphological transition to hyphal form. We tested the anticandidal activity of eugenol, main component of clove oil, and thymol, main component of thyme oil, alone or in combination, by investigating their ability to interfere with the architecture of the envelope of C. albicans. Both molecules alterated the morphogenesis of the envelope, but the effects of thymol were more pronounced than those of eugenol. Certain combinations of the two molecules led to a synergistic effect, which is interesting in the view of potentiating their inhibition of C. albicans colonisation and infectiousness.

In vitro cytotoxicity activity on several cancer cell lines of acridone alkaloids and N-phenylethyl-benzamide derivatives from Swinglea glutinosa (Bl.) Merr.

The methanol extract from the stems and fruits of Swinglea glutinosa (Rutaceae) afforded 11 known acridone alkaloids and three N-phenylethyl-benzamide derivatives, glycocitrine-IV, 1,3,5-trihydroxy-4-methoxy-10-methyl-2,8-bis(3-methylbut-2-enyl)acridin-9(10H)-one, 1,3,5- trihydroxy-2,8-bis(3-methylbut-2-enyl)-10-methyl-9-acridone, citbrasine, citrusinine-II, citrusinine-I, 5-dihydroxyacronycine, pyranofoline, 3,4-dihydro-3,5,8-trihydroxy-6-methoxy-2,2,7-trimethyl-2H-pyrano[2,3-a]acridin-12(7H)-one, 2,3-dihydro-4,9-dihydroxy-2-(2-hydroxy-propan-2-yl)-11-methoxy-10-methylfuro[3,2-b]acridin-5(10H)-one, bis-5-hydroxyacronycine, N-(2-{4-[(3,7-dimethylocta-2,6-dien-1-yl)oxy]phenyl}ethyl)benzamide, N-(2-{4-[(3,7-dimethyl-4-acethyl-octa-2,6-dien-1-yl)oxy]phenyl}ethyl)benzamide, and severine acetate. All compounds isolated were examined for their activity against three cancer cell lines: human lung carcinoma (COR-L23), human breast adenocarcinoma (MCF7), human melanoma (C32), and normal human fetal lung cell line, MRC-5. The acridones tested exhibited weak cytotoxicity but the amides showed moderate nonselective cytotoxic activity.