The allelopathic effects of aqueous Talinum triangulare (jacq.) willd extracts on the development of Lactuca sativa L. seedlings.

Plants that produce allelopathic compounds against weeds have emerged as a potential solution for the development of ecologically correct bioherbicides. Talinum triangulare is noteworthy in this regard, as its phytochemical composition encompasses flavonoids, alkaloids and other metabolites that can be used to develop inhibitory weed growth solutions. Lactuca sativa (lettuce) has been widely applied as a bioindicator species for bioherbicides and several chemicals, animal waste, water and soil quality, and atmospheric contamination, among others. In this context, this study aimed to assess the potential allelopathic effect of aqueous T. triangulare extracts on the development of L. sativa seedlings. A completely randomized design employing a 2x4 factorial scheme (shoot and root extracts) x the concentration of each extract (0, 2.5, 5, 7.5%) was applied, comprising four replications. Lactuca sativa seeds were sown on germitest papers soaked with the extracts in a germination chamber at 20°C. Physiological seed evaluations comprising the germination test, where normal and abnormal seedlings are counted on the seventh day after sowing, first normal seedling counts on the fourth day after sowing, and seedling and root length measurements. At the end of the germination test, L. sativa seedlings were separated for morphoanatomical characterizations and chlorophyll a fluorescence analyses. The T. triangulare extracts significantly influenced L. sativa root growth, with shoot extract exposure leading to more abnormal plants and lower root lengths at increasing concentrations and compared to the root extract. Root extract exposure led to evident cellular changes and lower non-photochemical quenching and unregulated dissipation quantum yields at a 5% exposure dose compared to shoot extract exposure. These findings suggest that both aqueous T. triangulare root and shoot extracts from 5% exposure doses exhibit high potential as bioherbicides, acting directly on plant structure, anatomy, quality, size and physiology.

Directional electrodes in deep brain stimulation: Results of a survey by the European Association of Neurosurgical Societies (EANS).

Introduction: Directional Leads (dLeads) represent a new technical tool in Deep Brain Stimulation (DBS), and a rapidly growing population of patients receive dLeads. Research question: The European Association of Neurosurgical Societies(EANS) functional neurosurgery Task Force on dLeads conducted a survey of DBS specialists in Europe to evaluate their use, applications, advantages, and disadvantages. Material and methods: EANS functional neurosurgery and European Society for Stereotactic and Functional Neurosurgery (ESSFN) members were asked to complete an online survey with 50 multiple-choice and open questions on their use of dLeads in clinical practice. Results: Forty-nine respondents from 16 countries participated in the survey (n = 38 neurosurgeons, n = 8 neurologists, n = 3 DBS nurses). Five had not used dLeads. All users reported that dLeads provided an advantage (n = 23 minor, n = 21 major). Most surgeons (n = 35) stated that trajectory planning does not differ when implanting dLeads or conventional leads. Most respondents selected dLeads for the ability to optimize stimulation parameters (n = 41). However, the majority (n = 24), regarded time-consuming programming as the main disadvantage of this technology. Innovations that were highly valued by most participants included full 3T MRI compatibility, remote programming, and closed loop technology. Discussion and conclusion: Directional leads are widely used by European DBS specialists. Despite challenges with programming time, users report that dLeads have had a positive impact and maintain an optimistic view of future technological advances.

Biomarkers of pollution by glyphosate in the lichens, Parmotrema tinctorium and Usnea barbata.

Glyphosate is a herbicide commonly used in agriculture for weed control. Current agricultural production demands vast amounts of this product, which are applied by ground or aerial spraying. The concomitant aerial currents promote glyphosate drift to vegetated or urban areas. In this context, we hypothesized that the lichens, Parmotrema tinctorum and Usnea barbata, could be sensitive to the action of glyphosate and therefore be used to bio-indicate the presence of this herbicide in areas affected by drift. Since living organisms respond in different ways to the action of herbicides, our interest was also to indicate biological markers responsive to the action of glyphosate, through concentrations and exposure times of the thallus, besides identifying the most sensitive species. We evaluated the effect of different concentrations (0.0, 4.8, 9.6, and 19.2 mg L-1) and exposure times (24, 48, and 72 hours) to glyphosate on the morphoanatomy, photobiont vitality, photosynthetic efficiency, and oxidative metabolism of the thalli. We found that the lichens, P. tinctorum and U. barbata, respond to glyphosate stress, with prospects for use in the biomonitoring of pollutant dispersal from plantation areas. When using P. tinctorum as a bioindicator, lichen morphoanatomy, photobiont vitality, and photosynthetic pigment concentration were efficient biomarkers for the effect of concentration and exposure time. For U. barbata, the lichenic morphoanatomy and the activity of SOD and APX enzymes were essential tools to indicate the herbicide action. Parmotrema tinctotum, however, was characterized as more sensitive in bio-indicating the presence of this herbicide to diagnose the air quality in urban areas or vegetation sectors adjacent to agricultural environments.

Chronic Cadmium Exposure Accelerates the Development of Atherosclerosis and Induces Vascular Dysfunction in the Aorta of ApoE-/- Mice.

Cadmium exposure is related to cardiovascular diseases, including hypertension, atherosclerosis, increased oxidative stress, endothelial dysfunction, and specific biochemical changes induced by this metal. Thus, we aimed to investigate whether cadmium exposure induces endothelial dysfunction, accelerates atherosclerotic plaque formation in the aorta, and enhances oxidative stress in apolipoprotein E knockout (ApoE-/-) mice. Experiments were performed in 14-week-old male wild-type and ApoE-/- mice. ApoE-/- mice received cadmium (CdCl2 100 mg/L in drinking water for 28 days) or vehicle (distilled water). After treatment, vascular reactivity to phenylephrine, acetylcholine, and sodium nitroprusside was analyzed using isolated aorta. Bone marrow cells were isolated to assess the production of nitric oxide and reactive oxygen and nitrogen species. ApoE-/- cadmium-treated mice had higher cholesterol levels than non-exposed mice. Cadmium exposure decreased the vasodilatation response to acetylcholine in aortic ring of ApoE-/- mice, though no changes in phenylephrine or sodium nitroprusside responses were observed. L-NAME reduced vasodilator responses to acetylcholine; this effect was lower in ApoE-/- cadmium-treated mice, suggesting reduction in nitric oxide (NO) bioavailability. Moreover, in bone marrow cells, cadmium decreased cytoplasmic levels of NO and increased superoxide anions, hydrogen peroxide, and peroxynitrite in ApoE-/- mice. Morphological analysis showed that cadmium exposure increased plaque deposition in the aorta by approximately 3-fold. Our results suggest that cadmium exposure induces endothelial dysfunction in ApoE-/- mice. Moreover, cadmium increased total cholesterol levels, which may promote the early development of atherosclerosis in the aorta of ApoE-/- mice. Our findings support the hypothesis that cadmium exposure might increase the risk of atherosclerosis.

Pouteria torta: a native species of the Brazilian Cerrado as a bioindicator of glyphosate action / Pouteria torta: espécie native do Cerrado Brasileiro como bioindicadora da ação do glyphosate

Abstract In Brazil, the expansion of agricultural activity and the associated indiscriminate use of herbicides such as glyphosate is directly related to the loss of biodiversity in the Cerrado. The identification of plant species as bioindicators of herbicide action, especially species native to the area, can help in monitoring the impacts of xenobiotics in the remaining Cerrado. Thus, this study was designed to evaluate the possible use of the native Cerrado species Pouteria torta as a bioindicator of glyphosate action via changes in physiological performance. At 16 months after sowing, the effect of glyphosate was evaluated by applying the following doses: 0 (control), 25, 50, 100, 200, 400, 800, and 1200 g a.e. ha-1. In response to glyphosate, P. torta exhibited reductions in photosynthesis and chloroplastid pigment content, as well as accumulation of shikimic acid and the occurrence of chlorosis and necrosis. These changes demonstrate the high sensitivity of P. torta to glyphosate and its potential for use as a bioindicator of this herbicide.

Resumo No Brasil, a expansão da atividade agrícola, aliada a utilização indiscriminada de herbicidas como o glyphosate, possui relação direta com a perda da biodiversidade no Cerrado. A identificação de espécies vegetais bioindicadoras da ação de herbicidas, particularmente as nativas do Cerrado, pode auxiliar em processos de monitoramento dos impactos desse xenobiótico nas remanescentes do Cerrado. Assim, este estudo foi projetado para avaliar o possível uso de Pouteria torta, espécie nativa do cerrado, como bioindicadora da ação do glyphosate via mudanças na sua performance fisiológica. Após 16 meses de semeadura, o efeito do glyphosate foi avaliado quando aplicadas as seguintes doses: 0 (controle), 25, 50, 100, 200, 400, 800 e 1200 g e. a. ha-1. Em reposta ao glyphosate, as plantas de P. torta apresentaram redução na sua performance do processo fotossintético e no conteúdo de pigmentos cloroplastídicos, além do acúmulo de ácido chiquímico e da ocorrência de cloroses e necroses. Essas alterações demonstram a alta sensibilidade de P. torta ao glyphosate, o que potencializa a sua utilização como bioindicadora da ação desse herbicida.

Computational engineering of cellulase Cel9A-68 functional motions through mutations in its linker region.

Microbial cellulosic degradation by cellulases has become a complementary approach for biofuel production. However, its efficiency is hindered by the recalcitrance of cellulose fibres. In this context, computational protein design methods may offer an efficient way to obtain variants with improved enzymatic activity. Cel9A-68 is a cellulase from Thermobifida fusca that is still active at high temperatures. In a previous work, we described a collective bending motion, which governs the overall cellulase dynamics. This movement promotes the approximation of its CBM and CD structural domains (that are connected by a flexible linker). We have identified two residues (G460 and P461) located at the linker that act as a hinge point. Herein, we applied a new level of protein design, focusing on the modulation of this collective motion to obtain cellulase variants with enhanced functional dynamics. We probed whether specific linker mutations would affect Cel9A-68 dynamics through computational simulations. We assumed that P461G and G460+ (with an extra glycine) constructs would present enhanced interdomain motions, while the G460P mutant would be rigid. From our results, the P461G mutation resulted in a broader exploration of the conformational space, as confirmed by clustering and free energy analyses. The WT enzyme was the most rigid system. However, G460P and P460+ explored distinct conformational states described by opposite directions of low-frequency normal modes; they sampled preferentially closed and open conformations, respectively. Overall, we highlight two significant findings: (i) all mutants explored larger conformational spaces than the WT; (ii) the selection of distinct conformational populations was intimately associated with the mutation considered. Thus, the engineering of Cel9A-68 motions through linker mutations may constitute an efficient way to improve cellulase activity, facilitating the disruption of cellulose fibres.

Reference range of gestational uterine artery resistance index in small canine breeds.

The objectives of this study were to evaluate the uterine artery blood flow during the second half of normal pregnancy in small breed dogs and to determine the RI reference values of this artery in these bitches. Fifty-two, 1.5-6.5 kg, purebred healthy pregnant bitches were included in this study. Doppler ultrasonographic examinations of the uterus were performed every 10 days from Day 30 of the estrous cycle to parturition. Peak systolic velocity (PSV) and end diastolic velocity (EDV) of the uterine artery were measured while RI [(PSV-EDV)/PSV] was automatically calculated. Values of PSV, EDV and RI were analyzed by repeated measures ANOVA followed by Tukey test using age, body weight, litter size and parity as covariates. Resistance index reference ranges were constructed by regressing this index on gestational age. Equation of the polynomial regression curves was used to calculate the mean, 95th and 5th centiles for each gestational age (GA). A gradual increase of PSV (P < 0.01) and EDV (P < 0.01) and a decrease in RI (P < 0.01) were found throughout the study period. PSV and EDV were influenced by litter size (P < 0.05), while RI was not. None of the Doppler parameters were influenced by age, body weight or parity. A second-degree polynomial described the relationship between RI of uterine artery and GA in the different time points: [RI = 0.993 + 8.4x10-5 x GA2- 0.0117 x GA]. It is concluded that uterine artery blood flow progressively increased throughout normal pregnancy in small breed bitches. In addition, reference ranges of uterine artery RI were 0.64-0.79, 0.57 to 0.75, 0.53 to 0.71 and 0.52 to 0.66 on Days 30, 40, 50 and 60 of gestation, respectively.

Quality of Life Scale and symptomatology of schizophrenic patients - A systematic review

Background: The Quality of Life Scale (QLS) was developed to assess the quality of life of patients with schizophrenia, by Heinrichs, Hanlon and Carpenter, in 1984. Objectives: This systematic review analysed the scientific evidence produced from the QLS results and its relationship with the symptomatology of patients with schizophrenia. Methods: An electronic search was conducted on Pubmed/Medline and Scopus to identify relevant papers published within the last ten years (January 2007 to December 2016). The inclusion criteria were: studies whose samples included only outpatients with schizophrenia; studies whose aim was to compare the QLS results with the symptomatology of schizophrenia; studies written in English. The PRISMA criteria for reporting systematic reviews and meta-analyses were used. Results: Twelve studies were included in this systematic review. A total of 1645 patients with schizophrenia from four different countries were analysed. Ten articles used a cross-sectional study methodology and 2 articles involved a longitudinal study. Conclusions: Synthesis suggests that quality of life/functioning in patients with schizophrenia can be influenced by negative symptoms. Nevertheless, in relation to positive and depressive symptoms, the results are not congruent nor consistent. Therefore, this literature review indicated that more research is needed in order to obtain better evidence with regards to the influence of that symptomatology on the quality of life/functioning in patients with schizophrenia

No disponible

Morphological changes of the internal carotid artery: prevalence and characteristics. A clinical and ultrasonographic study in a series of 19 804 patients over 25 years old.

BACKGROUND AND PURPOSE: Morphological changes of the internal carotid arteries (McICA) are frequently found during cervical ultrasound studies. However, the etiology of McICA remains controversial. During this study, the prevalence and demographic characteristics of McICA, such as kinking, coiling or looping identified by Doppler ultrasound, were analysed and its relationship with vascular risk factors and stroke was assessed. METHODS: A retrospective study was performed by analysing 19 804 patients who were subjected to cervical ultrasonographic study between January 2000 and June 2012. The data were statistically analysed with SPSS® 20 and a multivariate logistic regression was performed. Statistical significance was accepted for P < 0.05 and 95% confidence intervals (CIs) were used. RESULTS: Morphological changes of the internal carotid arteries were present in 2678 patients (13.5%) and were unilateral in 61.6% of these cases. Carotid kinking was found in 80% of the patients, coiling in 16% and looping in 1%. In multivariate analysis, the presence of McICA was related to older groups (1.04; 95% CI, 1.04-1.05; P < 0.01), female gender (1.78; 95% CI, 1.64-1.94; P < 0.01), patients with hyperlipidemia (1.28; 95% CI, 1.17-1.40; P < 0.01), carotid thickness (1.22; 95% CI, 1.13-1.33; P < 0.01) and cardiac or cardioembolic disease (1.11; 95% CI, 1.01-1.21; P = 0.02). The results of this study indicate that kinking in the carotid artery was associated with ipsilateral cerebral ischemic events (1.43; 95% CI, 1.040-1.958; P < 0.05). CONCLUSION: Morphological changes of the internal carotid arteries were associated with aging, female gender and patients with hyperlipidemia, hypertension, diabetes and heart disease. Kinking was associated with ipsilateral cerebral ischemia.

Pouteria torta: a native species of the Brazilian Cerrado as a bioindicator of glyphosate action.

In Brazil, the expansion of agricultural activity and the associated indiscriminate use of herbicides such as glyphosate is directly related to the loss of biodiversity in the Cerrado. The identification of plant species as bioindicators of herbicide action, especially species native to the area, can help in monitoring the impacts of xenobiotics in the remaining Cerrado. Thus, this study was designed to evaluate the possible use of the native Cerrado species Pouteria torta as a bioindicator of glyphosate action via changes in physiological performance. At 16 months after sowing, the effect of glyphosate was evaluated by applying the following doses: 0 (control), 25, 50, 100, 200, 400, 800, and 1200 g a.e. ha-1. In response to glyphosate, P. torta exhibited reductions in photosynthesis and chloroplastid pigment content, as well as accumulation of shikimic acid and the occurrence of chlorosis and necrosis. These changes demonstrate the high sensitivity of P. torta to glyphosate and its potential for use as a bioindicator of this herbicide.

Echocardiographic and electrocardiographic parameters during the normal postpartum period in toy breeds of dogs.

The aim of this study was to evaluate echocardiographic and electrocardiographic parameters during the normal canine postpartum period. Twenty clinically healthy pregnant bitches of toy breeds (11 Miniature poodles, five Yorkshire terriers, two Maltese terriers and two Bichons Frises) were evaluated on days -3, 3, 10, 17, 24, 38, 52 and 80 relative to parturition (day 0). During the first postpartum week, the width of the interventricular septum in systole, the shortening fraction and the left atrium size decreased, while the left ventricle internal diameter in systole and end systolic stress increased. There were progressive decreases in the velocity of circumferential fibre shortening, stroke volume, cardiac output, and mitral E and A wave values. Systolic blood pressure increased markedly during the first postpartum week to gradually increase thereafter. Heart rate and corrected QT interval progressively decreased, while P wave amplitude increased. QRS complex amplitude decreased in the second week after parturition and then increased during the following weeks. In conclusion, there were changes in systolic function and some structural adaptive changes in the bitch during the first 80days postpartum. In addition, maternal heart rate and corrected QT interval decreased, while P wave and QRS amplitudes increased.

Performance of grain sorghum hybrids under drought stress using GGE biplot analyses.

The objective of this study was to estimate the adaptability and stability of grain sorghum hybrids grown under post-flowering water stress and non-stress conditions. The trials were carried out in Nova Porteirinha-MG during the season of 2014 and 2015, and in Teresina-PI in the 2014 season. Twenty-nine-grain sorghum hybrids were evaluated, in a randomized complete block design, with three replications. Plots consisted of four lines with 3 m long. The grain yield data were submitted to the individual variance analysis, having considered the effects of the hybrids as fixed and the other effects as random. The joint analysis was carried out, and when the interaction genotypes x environments was significant, the grain yield data were submitted to the adaptability and stability analysis by the GGE biplot method. A substantial reduction in the grain yield in environments with water stress was found. The highest yielding hybrids under water stress conditions in Nova Porteirinha-MG were 50A50, AG1080, AG1090, DKB550, DKB590, Jade, and BM737, and the highest yielding hybrids under the water stress in Teresina-PI were 1G282, 1G244, and A9721R. Considering all environments, the highest yielding hybrids were 1G282, DKB540, A9721R, 1G100, and AG1090.

Pouteria torta: a native species of the Brazilian Cerrado as a bioindicator of glyphosate action

Abstract In Brazil, the expansion of agricultural activity and the associated indiscriminate use of herbicides such as glyphosate is directly related to the loss of biodiversity in the Cerrado. The identification of plant species as bioindicators of herbicide action, especially species native to the area, can help in monitoring the impacts of xenobiotics in the remaining Cerrado. Thus, this study was designed to evaluate the possible use of the native Cerrado species Pouteria torta as a bioindicator of glyphosate action via changes in physiological performance. At 16 months after sowing, the effect of glyphosate was evaluated by applying the following doses: 0 (control), 25, 50, 100, 200, 400, 800, and 1200 g a.e. ha-1. In response to glyphosate, P. torta exhibited reductions in photosynthesis and chloroplastid pigment content, as well as accumulation of shikimic acid and the occurrence of chlorosis and necrosis. These changes demonstrate the high sensitivity of P. torta to glyphosate and its potential for use as a bioindicator of this herbicide.

Resumo No Brasil, a expansão da atividade agrícola, aliada a utilização indiscriminada de herbicidas como o glyphosate, possui relação direta com a perda da biodiversidade no Cerrado. A identificação de espécies vegetais bioindicadoras da ação de herbicidas, particularmente as nativas do Cerrado, pode auxiliar em processos de monitoramento dos impactos desse xenobiótico nas remanescentes do Cerrado. Assim, este estudo foi projetado para avaliar o possível uso de Pouteria torta, espécie nativa do cerrado, como bioindicadora da ação do glyphosate via mudanças na sua performance fisiológica. Após 16 meses de semeadura, o efeito do glyphosate foi avaliado quando aplicadas as seguintes doses: 0 (controle), 25, 50, 100, 200, 400, 800 e 1200 g e. a. ha-1. Em reposta ao glyphosate, as plantas de P. torta apresentaram redução na sua performance do processo fotossintético e no conteúdo de pigmentos cloroplastídicos, além do acúmulo de ácido chiquímico e da ocorrência de cloroses e necroses. Essas alterações demonstram a alta sensibilidade de P. torta ao glyphosate, o que potencializa a sua utilização como bioindicadora da ação desse herbicida.

The use of the color Doppler ultrasonography in the diagnosis and monitoring of an atypical case of giant-cell arteritis.

Giant Cell Arteritis (GCA) is a large vessels vasculitis that is typically characterised by headache, scalp tenderness, jaw claudication and visual disturbances. Temporal arteries color Doppler ultrasonography (CDUS) is a sensitive and non-invasive image technique used in the diagnosis of this disease. This work highlights the importance of CDUS in the diagnostic workup of GCA and also demonstrates it´s usefullness in the evaluation and documentation of the response to corticosteroids therapy in an atypical case of ACG.

Uterine blood flow evaluation in bitches suffering from cystic endometrial hyperplasia (CEH) and CEH-pyometra complex.

Doppler ultrasound is a useful diagnosis tool to evaluate uterine blood flow in different canine reproductive states. The aim of this study was to describe and compare uterine blood flow in bitches suffering from cystic endometrial hyperplasia (CEH) and CEH-pyometra complex (CEH-P). Ninety diestrous bitches were clinically, hematologically, and ultrasonographically classified into four groups: (1) clinical signs, leukocytosis, CEH, and uterine luminal contents (CEH-P, n = 31); (2) asymptomatic bitches with CEH and uterine contents (CEH-C, n = 15); (3) asymptomatic bitches with CEH without uterine contents (CEH, n = 16); and (4) normal diestrous bitches (ND, n = 28). The widest cross-sectional diameter and uterine wall thickness (W) of uterine horns were measured using two-dimensional ultrasound. Peak systolic velocity and end diastolic velocity of uterine arteries were measured by Doppler ultrasound in all the bitches. Peak systolic velocity and end diastolic velocity were higher in CEH-P than in CEH-C, CEH, and ND (P < 0.01); although both parameters did not show differences among the latter three groups (P > 0.1). Conversely, resistance index (RI) reported lower values in CEH-P than that in the other three groups (P < 0.01), being ND higher (P < 0.01) than both CEH-C and CEH which did not differ between themselves (P > 0.1). When all the bitches were considered, correlation between RI and cross-sectional diameter was r = -0.69 (P < 0.01) and between RI and uterine wall thickness was r = -0.02 (P > 0.1). It is concluded that the uterine artery blood flow velocity of bitches suffering from pyometra was higher, not only from normal bitches, but also from females with endometrial hyperplasia. Furthermore, endometrial hyperplasia, accompanied or not by luminal contents, had a higher blood flow velocity than normal uterus. Hemodynamic parameters appear as useful markers to differentiate uterine pathologic conditions.

Bidimensional and Doppler ultrasonographic evaluation of postpartum uterine involution in the queen.

The aim of this study was to describe bidimensional and Doppler ultrasonographic changes of uterine involution during normal feline puerperium. Secondary, the postpartum vaginal discharge was described. Twelve pregnant female cats were included in this study. After queening, vulvar discharge was grossly and microscopically examined daily. Bidimensional and Doppler ultrasonographic examinations of the uterus were performed on Days -4 to -2, 4, 11, 18, and 25 from parturition. Total uterine diameter, uterine wall thickness, uterine lumen contents, peak systolic velocity, end diastolic velocity, and resistance index of uterine arteries were measured. The cats presented serosanguineous vulvar discharge for a mean of 3 ± 1 days after parturition, and the cytology revealed 70% to 80% of erythrocytes, which progressively decreased up to Day 13. Immediately after parturition, there were less than 20% neutrophils, and this percentage gradually diminished to 0% to 1% at the end of the study. Uterine total diameter diminished up to Day 25 (P < 0.01), when ultrasonographic uterine dimensions were similar to that of anestrus. A progressive decrease of uterine wall thickness (P < 0.05), uterine lumen contents (P < 0.01), peak systolic velocity (P < 0.01), and end diastolic velocity (P < 0.01) was found throughout the study period. Conversely, resistance index increased during the first week after parturition (P < 0.01). It is concluded that the uterine artery blood flow progressively decreased during the first 25 days after parturition, which was associated with the bidimensional ultrasonographic regression of the organ. Although lochial discharge disappeared far before ultrasonographic involution, cytologic findings further corroborated the duration of this regression process.

Toll-like receptor 4 contributes to vascular remodelling and endothelial dysfunction in angiotensin II-induced hypertension.

BACKGROUND AND PURPOSE: Toll-like receptor 4 (TLR4) signalling contributes to inflammatory cardiovascular diseases, but its role in hypertension and the associated vascular damage is not known. We investigated whether TLR4 activation contributed to angiotensin II (AngII)-induced hypertension and the associated vascular structural, mechanical and functional alterations. EXPERIMENTAL APPROACH: AngII was infused (1.44 mg · kg(-1) · day(-1), s.c.) for 2 weeks in C57BL6 mice, treated with a neutralizing anti-TLR4 antibody or IgG (1 µg · day(-1); systolic BP (SBP) and aortic cytokine levels were measured. Structural, mechanical and contractile properties of aortic and mesenteric arterial segments were measured with myography and histology. RT-PCR and Western blotting were used to analyse these tissues and cultured vascular smooth muscle cells (VSMC) from hypertensive rats (SHR). KEY RESULTS: Aortic TLR4 mRNA levels were raised by AngII infusion. Anti-TLR4 antibody treatment of AngII-treated mice normalised: (i) increased SBP and TNF-α, IL-6 and CCL2 levels; (ii) vascular structural and mechanical changes; (iii) altered aortic phenylephrine- and ACh-induced responses; (iv) increased NOX-1 mRNA levels, superoxide anion production and NAD(P)H oxidase activity and effects of catalase, apocynin, ML-171 and Mito-TEMPO on vascular responses; and (v) reduced NO release and effects of L-NAME on phenylephrine-induced contraction. In VSMC, the MyD88 inhibitor ST-2825 reduced AngII-induced NAD(P)H oxidase activity. The TLR4 inhibitor CLI-095 reduced AngII-induced increased phospho-JNK1/2 and p65 NF-κB subunit nuclear protein expression. CONCLUSIONS AND IMPLICATIONS: TLR4 up-regulation by AngII contributed to the inflammation, endothelial dysfunction, vascular remodelling and stiffness associated with hypertension by mechanisms involving oxidative stress. MyD88-dependent activation and JNK/NF-κB signalling pathways participated in these alterations.

Effect of GnRH analogs in postnatal domestic cats.

The aim of this study was to reproductively assess the clinical and hormonal effects of a GnRH agonist (AG) and an antagonist (AN) administered during the postnatal period in domestic cats. Forty-eight male and female postnatal kittens were randomly assigned to deslorelin acetate 1.6 mg subcutaneous (AG; n = 16), acyline 33 µg/100 g subcutaneous weekly for 3 months (AN; n = 16), or control (CO; n = 16) which remained untreated. The cats were followed up (behavioral observation, physical examination, fecal sexual steroid determinations, mating test, and pregnancy diagnosis) up to puberty. Puberty was delayed (weeks) in the AG animals (62.9 ± 3.5; P < 0.01) but not in the AN (15.5 ± 1.7; P > 0.05) when they were compared with CO kittens (13.4 ± 0.4). Fifteen (15/16) of the AN and CO animals, and only 11 of 16 cats of the AG group were fertile (P > 0.1). No differences were found in body weight (P > 0.1) and measurements (P > 0.1), libido (P > 0.1) and in the appearance of side effects (P > 0.1; except a pyometra in an AG female) among groups. In both AG- and AN-treated males (testosterone; P < 0.01) and females (estradiol-17ß; P < 0.01) fecal hormone concentrations were lower than in CO group during the first five postnatal weeks but not later. It is concluded that the neonatal administration of these AG and AN decreased fecal sexual steroids during the first postnatal weeks causing, the agonists but not the antagonist, a significant, reversible delay in puberty appearance.

Doppler ultrasonographic assessment of uterine arteries during normal canine puerperium.

The aim of this study was to describe Doppler ultrasonographic changes of uterine arteries during normal canine puerperium. Eight healthy, pure-bred bitches, were ultrasonographically assessed during the postpartum period on Days -3, 3, 10, 17, 24, 38, 52 and 80 (Day 0 defined as the day of parturition). Total horn diameters (TD) and endometrium thickness (E) were evaluated. Color Doppler was used to localize uterine arteries at both sides of the body and pulsed-wave Doppler was performed to obtain the waveforms. Peak systolic velocity (PSV) and end diastolic velocity (EDV) were measured. Resistance index [(PSV-EDV)/PSV] was automatically calculated. Values of TD, E, PSV, EDV and RI were analyzed by repeated measures ANOVA followed by LSD test (SPSS 18.0; SPSS, Chicago, IL, USA). A correlation analysis was also carried out between RI and TD. A progressive decrease of TD (P<0.01) and E (P<0.01) was found in the course of the study. A gradual diminution of PSV (P<0.01) and EDV (P<0.01) and an increase of RI (P<0.01) were also found throughout the study period. The resistance index negatively correlated with TD (r=-0.46; P<0.01) and E (r=-0.44; P<0.01) while the ultrasonographic and vascular changes in this period are concurrent with regenerative changes in the glandular and epithelial structures of the uterus. It is concluded that uterine artery RI progressively increased during normal canine puerperium, associated to the two-dimensional ultrasonographic regression of the organ.

Efeitos cardiorrespiratórios da metadona, pelas vias intramuscular e intravenosa, em cadelas submetidas à ovariossalpingo-histerectomia / Cardiorespiratory effects of methadone, by intramuscular or intravenous injection, in female dogs submitted to ovariohysterectomy

A metadona é um opioide pouco utilizado na medicina veterinária, e há, ainda, questionamentos quanto ao seu uso. Desse modo, comparou-se o emprego da metadona, administrada pelas vias IM e IV, e avaliaram-se seus efeitos sobre as características cardiorrespiratórias e os tempos de extubação e recuperação em cadelas submetidas à ovariossalpingo-histerectomia. Utilizaram-se 16 cadelas, pré-medicadas com levomepromazina, 0.6mg/kg, IM. Após 20 minutos, a indução anestésica foi feita com propofol, 5mg/kg, IV, e a manutenção com isoflurano. Transcorridos 10 minutos, os animais receberam metadona, 0.3mg/kg, pelas vias IM - grupo GIM - e IV - grupo GIV. As mensurações das frequências cardíaca (FC) e respiratória (FR), pressão arterial média (PAM), temperatura esofágica (TE), pressão parcial de dióxido de carbono (EtCO2) e saturação de oxi-hemoglobina (SpO2) foram registradas antes da administração do opioide (T0), após 20 minutos (T1) e a cada 10 minutos da administração até 60 minutos (T2 a T5). Usou-se a análise de perfil (5%). Com relação à FC, PAM, FR, EtCO2, TE e SpO2, não foram observadas diferenças significativas entre grupos e momentos. Observaram-se tempos de extubação e recuperação maiores no GIV. É possível concluir que a administração IV e a IM da metadona não produzem alterações nas características cardiorrespiratórias em cadelas.

Methadone is a little used opioid in veterinary practice, and there are still questions about its use. The objective of this study was to evaluate the effects of intramuscular (IM) or intravenous (IV) administration of methadone on cardiopulmonary parameters and times of extubation and recovery in female dogs submitted to ovariohysterectomy. Sixteen adult female dogs were used and premedicated with levomepromazine (0.6mg/kg, IM). After 20 minutes, propofol (5mg/kg, IV) was used for induction and anesthesia was maintained with isoflurane. After 10 minutes, methadone at 0.3mg/kg was administered intravenously in IVG and intramuscularly in IMG. The measurement of heart (HR) and respiratory rates (RR), median arterial pressure (MAP), esophagic temperature (ET) and concentration of end-tidal carbon dioxide (PE'CO2) was performed immediately before the administration of the opioid (T0), after 20 minutes (T1) and then at 10-minute intervals (T2, T3, T4 and T5). The statistical analysis used was profile (5%). HR, APM, RR, PE'CO2, BT and SpO2 did not differ significantly among times or between groups at any time. Times of extubation and recovery were higher in IVG. It is possible to conclude that IV and IM administration of methadone did not produce changes in the cardiorespiratory parameters of that specie.