Ultrasound-assisted periconal ocular blockade in rabbits

ObjectiveThis study aimed to evaluate the benefit and specifically the feasibility of using ultrasound in ophthalmologic periconal block, and the occurrence of complications.Study designProspective experimental study.AnimalsTen healthy New Zealand White rabbits (6-8months of age), weighing 2.0-3.5kg.MethodsRabbits were anesthetized by intramuscular injection of acepromazine (1mgkg(-1)), ketamine (30mgkg(-1)) and xylazine (3mgkg(-1)). Ultrasound-assisted periconal block with lidocaine was performed on 18 eyes. Intraocular pressure was measured by applanation tonometry whereas corneal sensitivity was assessed using an esthesiometer, before and after each periconal anesthesia.ResultsIn all 18 eyes, it was possible to adequately visualize the needle shaft within the periconal space, as well as muscular cone, optic nerve and local anesthetic solution spread. Lidocaine 2% without epinephrine (0.790.19mL) was injected into the periconal space. There was no statistical difference between the intraocular pressure (meanSD) measured before (10.9 +/- 2.9mmHg) and after (11.9 +/- 3.8mmHg) the periconal anesthesia (p=0.38). The effectiveness of the ultrasound-assisted technique was shown according to the values for corneal sensitivity, assessed before and after periconal anesthesia (p<0.0001). Complications were not observed in this study.ConclusionsEye ultrasonography allowed visualization of all anatomic structures necessary to perform a periconal block, as well as the needle insertion and anesthetic spread in real time. Further studies are required to prove the real potential of ultrasound for reducing the incidence of complications associated with ophthalmic blocks, especially when anatomic disorders of the eye could potentially increase the risk.Clinical relevanceUltrasonography is a painless, noninvasive tool that may improve safety of ophthalmic regional blocks, potentially by reducing the prevalence of globe perforation or penetration of the optic nerve associated with the needle-based techniques.

Neonatal anoxia in rats: hippocampal cellular and subcellular changes related to cell death and spatial memory

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

Molecular detection of the blood meal source of sand flies (Diptera: Psychodidae) in a transmission area of American cutaneous leishmaniasis, Parana State, Brazil

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Effects of castration and of testosterone replacement on alpha(1)-adrenoceptor subtypes in the rat vas deferens

The contractions of the rat vas deferens in response to noradrenaline are mediated through alpha(1A)-adrenoceptors. We observed participation of alpha(1B)-adrenoceptors in these contractions after castration. We now investigated the time course of this plasticity and the effects of testosterone by determining the actions of competitive antagonists on noradrenaline-induced contractions after 7, 14, 21 and 30 days of castration. BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) antagonised noradrenaline-induced contractions in control and castrated rats with low pA(2) values (approximately = 6.8). In control vas deferens, WB 4101 (2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane hydrochloride) had a slope in the Schild plot no different from 1.0, while slopes lower than 1.0 (approximately 0.6) were observed for vas deferens from castrated rats. Chloroethylclonidine was ineffective in the control vas while it inhibited noradrenaline-induced contractions in vasa from castrated rats and converted the complex antagonism by WB 4101 into simple competitive antagonism. Treatment of castrated rats with testosterone prevented the effects of castration. The results suggest that alpha(1B)-adrenoceptors are detectable in vas deferens from at least the 7th through the 30th day after castration and that testosterone prevents this plasticity.

Nanoencapsulation enhances the post-emergence herbicidal activity of atrazine against mustard plants

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

Avaliação dos mecanismos moleculares envolvidos na instalação da resistência periférica à insulina em camundongos portadores de caquexia tumoral

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Host-Specificity of Myxoma Virus: Pathogenesis of South American and North American Strains of Myxoma Virus in Two North American Lagomorph Species

The pathogenesis of South American and North American myxoma viruses was examined in two species of North American lagomorphs, Sylvilagus nuttallii (mountain cottontail) and Sylvilagus audubonii (desert cottontail) both of which have been shown to have the potential to transmit the South American type of myxoma virus. Following infection with the South American strain (Lausanne, Lu), S. nuttallii developed both a local lesion and secondary lesions on the skin. They did not develop the classical myxomatosis seen in European rabbits (Oryctolagus cuniculus). The infection at the inoculation site did not resolve during the 20-day time course of the trial and contained transmissible virus titres at all times. In contrast, S. audubonii infected with Lu had very few signs of disseminated infection and partially controlled virus replication at the inoculation site. The prototype Californian strain of myxoma virus (MSW) was able to replicate at the inoculation site of both species but did not induce clinical signs of a disseminated infection. In S. audubonii, there was a rapid response to MSW characterized by a massive T lymphocyte infiltration of the inoculation site by day 5. MSW did not reach transmissible titres at the inoculation site in either species. This might explain why the Californian myxoma virus has not expanded its host-range in North America.

Learned helplessness in the rat: Effect of response topography in a within-subject design

Three experiments investigated learned helplessness in rats manipulating response topography within-subject and different intervals between treatment and tests among groups. In Experiment 1, rats previously exposed to inescapable shocks were tested under an escape contingency where either jumping or nose poking was required to terminate shocks: tests were run either 1, 14 or 28 days after treatment. Most rats failed to jump, as expected, but learned to nose poke, regardless of the interval between treatment and tests and order of testing. The same results were observed in male and female rats from a different laboratory (Experiment 2) and despite increased exposure to the escape contingencies using a within-subject design (Experiment 3). Furthermore, no evidence of helplessness reversal was observed, since animals failed to jump even after having learned to nose-poke in a previous test session. These results are not consistent with a learned helplessness hypothesis, which claims that shock (un)controllability is the key variable responsible for the effect. They are nonetheless consistent with the view that inescapable shocks enhance control by irrelevant features of the relationship between the environment and behavior. (C) 2010 Elsevier B.V. All rights reserved.

Lymphatic fluctuation in the parenchymal remodeling stage of acute interstitial pneumonia, organizing pneumonia, nonspecific interstitial pneumonia and idiopathic pulmonary fibrosis

Because the superficial lymphatics in the lungs are distributed in the subpleural, interlobular and peribroncovascular interstitium, lymphatic impairment may occur in the lungs of patients with idiopathic interstitial pneumonias (IIPs) and increase their severity. We investigated the distribution of lymphatics in different remodeling stages of IIPs by immunohistochemistry using the D2-40 antibody. Pulmonary tissue was obtained from 69 patients with acute interstitial pneumonia/diffuse alveolar damage (AIP/DAD, N = 24), cryptogenic organizing pneumonia/organizing pneumonia (COP/OP, N = 6), nonspecific interstitial pneumonia (NSIP/NSIP, N = 20), and idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP, N = 19). D2-40+ lymphatic in the lesions was quantitatively determined and associated with remodeling stage score. We observed an increase in the D2-40+ percent from DAD (6.66 +/- 1.11) to UIP (23.45 +/- 5.24, P = 0.008) with the advanced process of remodeling stage of the lesions. Kaplan-Meier survival curves showed a better survival for patients with higher lymphatic D2-40+ expression than 9.3%. Lymphatic impairment occurs in the lungs of IIPs and its severity increases according to remodeling stage. The results suggest that disruption of the superficial lymphatics may impair alveolar clearance, delay organ repair and cause severe disease progress mainly in patients with AIP/DAD. Therefore, lymphatic distribution may serve as a surrogate marker for the identification of patients at greatest risk for death due to IIPs.

Glucocorticoids are required for meal-induced changes in the expression of hypothalamic neuropeptides

Glucocorticoid deficiency is associated with a decrease of food intake. Orexigenic peptides, neuropeptide Y (NPY) and agouti related protein (AgRP), and the anorexigenic peptide proopiomelanocortin (POMC), expressed in the arcuate nucleus of the hypothalamus (ARC), are regulated by meal-induced signals. Orexigenic neuropeptides, melanin-concentrating hormone (MCH) and orexin, expressed in the lateral hypothalamic area (LHA), also control food intake. Thus, the present study was designed to test the hypothesis that glucocorticoids are required for changes in the expression of hypothalamic neuropeptides induced by feeding. Male Wistar rats (230-280 g) were subjected to ADX or sham surgery. ADX animals received 0.9% NaCl in the drinking water, and half of them received corticosterone in the drinking water (B: 25 mg/L, ADX + B). Six days after surgery, animals were fasted for 16 h and they were decapitated before or 2 h after refeeding for brain tissue and blood collections. Adrenalectomy decreased NPY/AgRP and POMC expression in the ARC in fasted and refed animals, respectively. Refeeding decreased NPY/AgRP and increased POMC mRNA expression in the ARC of sham and ADX + B groups, with no effects in ADX animals. The expression of MCH and orexin mRNA expression in the LHA was increased in ADX and ADX + B groups in fasted condition, however there was no effect of refeeding on the expression of MCH and orexin in the LHA in the three experimental groups. Refeeding increased plasma leptin and insulin levels in sham and ADX + B animals, with no changes in leptin concentrations in ADX group, and insulin response to feeding was lower in this group. Taken together, these data demonstrated that circulating glucocorticoids are required for meal-induced changes in NPY, AgRP and POMC mRNA expression in the ARC. The lower leptin and insulin responses to feeding may contribute to the altered hypothalamic neuropeptide expression after adrenalectomy. (C) 2012 Elsevier Ltd. All rights reserved.

Suicide rates and income in Sao Paulo and Brazil: a temporal and spatial epidemiologic analysis from 1996 to 2008

Background: In a classical study, Durkheim noted a direct relation between suicide rates and wealth in the XIX century France. Since that time, several studies have verified this relationship. It is known that suicide rates are associated with income, although the direction of this association varies worldwide. Brazil presents a heterogeneous distribution of income and suicide across its territory; however, evaluation for an association between these variables has shown mixed results. We aimed to evaluate the relationship between suicide rates and income in Brazil, State of Sao Paulo (SP), and City of SP, considering geographical area and temporal trends. Methods: Data were extracted from the National and State official statistics departments. Three socioeconomic areas were considered according to income, from the wealthiest (area 1) to the poorest (area 3). We also considered three regions: country-wide (27 Brazilian States and 558 Brazilian micro-regions), state-wide (645 counties of SP State), and city-wide (96 districts of SP city). Relative risks (RR) were calculated among areas 1, 2, and 3 for all regions, in a cross-sectional approach. Then, we used Joinpoint analysis to explore the temporal trends of suicide rates and SaTScan to investigate geographical clusters of high/low suicide rates across the territory. Results: Suicide rates in Brazil, the State of SP, and the city of SP were 6.2, 6.6, and 5.4 per 100,000, respectively. Taking suicide rates of the poorest area (3) as reference, the RR for the wealthiest area was 1.64, 0.88, and 1.65 for Brazil, State of SP, and city of SP, respectively (p for trend <0.05 for all analyses). Spatial cluster of high suicide rates were identified at Brazilian southern (RR = 2.37), state of SP western (RR = 1.32), and city of SP central (RR = 1.65) regions. A direct association between income and suicide were found for Brazil (OR = 2.59) and the city of SP (OR = 1.07), and an inverse association for the state of SP (OR = 0.49). Conclusions: Temporospatial analyses revealed higher suicide rates in wealthier areas in Brazil and the city of SP and in poorer areas in the State of SP. We further discuss the role of socioeconomic characteristics for explaining these discrepancies and the importance of our findings in public health policies. Similar studies in other Brazilian States and developing countries are warranted.

Exercise training prevents oxidative stress and ubiquitin-proteasome system overactivity and reverse skeletal muscle atrophy in heart failure

Background: Heart failure (HF) is known to lead to skeletal muscle atrophy and dysfunction. However, intracellular mechanisms underlying HF-induced myopathy are not fully understood. We hypothesized that HF would increase oxidative stress and ubiquitin-proteasome system (UPS) activation in skeletal muscle of sympathetic hyperactivity mouse model. We also tested the hypothesis that aerobic exercise training (AET) would reestablish UPS activation in mice and human HF. Methods/Principal Findings: Time-course evaluation of plantaris muscle cross-sectional area, lipid hydroperoxidation, protein carbonylation and chymotrypsin-like proteasome activity was performed in a mouse model of sympathetic hyperactivity-induced HF. At the 7th month of age, HF mice displayed skeletal muscle atrophy, increased oxidative stress and UPS overactivation. Moderate-intensity AET restored lipid hydroperoxides and carbonylated protein levels paralleled by reduced E3 ligases mRNA levels, and reestablished chymotrypsin-like proteasome activity and plantaris trophicity. In human HF (patients randomized to sedentary or moderate-intensity AET protocol), skeletal muscle chymotrypsin-like proteasome activity was also increased and AET restored it to healthy control subjects' levels. Conclusions: Collectively, our data provide evidence that AET effectively counteracts redox imbalance and UPS overactivation, preventing skeletal myopathy and exercise intolerance in sympathetic hyperactivity-induced HF in mice. Of particular interest, AET attenuates skeletal muscle proteasome activity paralleled by improved aerobic capacity in HF patients, which is not achieved by drug treatment itself. Altogether these findings strengthen the clinical relevance of AET in the treatment of HF.

Plasma corticosterone levels in mouse models of pain

Background: Pain markedly activates the hypothalamic-pituitary-adrenal (HPA) axis and increases plasma corticosterone release interfering significantly with nociceptive behaviour as well as the mechanism of action of analgesic drugs. Aims/Methods: In the present study, we monitored the time course of circulating corticosterone in two mouse strains (C57Bl/6 and Balb/C) under different pain models. In addition, the stress response was investigated following animal handling, intrathecal (i.t.) manipulation and habituation to environmental conditions commonly used in nociceptive experimental assays. We also examined the influence of within-cage order of testing on plasma corticosterone. Results: Subcutaneous injection of capsaicin precipitated a prompt stress response whereas carrageenan and complete Freund's adjuvant induced an increased corticosterone release around the third hour post-injection. However, carrageenan induced a longer increased corticosterone in C57Bl/6 mice. In partial sciatic nerve ligation, neuropathic pain model corticosterone increased only in the first days whereas mechanical hypersensitivity remained much longer. Animal handling also represents an important stressor whereas the i.t. injection per se does not exacerbate the handling-induced stress response. Moreover, the order of testing animals from the same cage does not interfere with plasma corticosterone levels in the intrathecal procedure. Animal habituation to the testing apparatus also does not reduce the immediate corticosterone increase as compared with non-habituated mice. Conclusion: Our data indicate that HPA axis activation in acute and chronic pain models is time dependent and may be dissociated from evoked hyperalgesia. Therefore, HPA-axis activation represents an important variable to be considered when designing experimental assays of persistent pain as well as for interpretation of data.

An evaluation of dosimetric characteristics of MAGIC gel modified by adding formaldehyde (MAGIC-f)

Purpose: To evaluate the dosimetric characteristics of a new formulation of MAGIC gel, called MAGIC-f, which contains the addition of 3.3% formaldehyde, resulting in a gel with increased thermal stability. Methods: MAGIC-f gel was prepared and stored in hermetically sealed plastic containers. After irradiation, magnetic resonance images (MRI) were acquired to evaluate dose and dose distribution. Dosimetric characterization was performed by means of depth dose measurements, dose response sensitivity and linearity, temporal stability, energy and dose rate dependence, dose integration using sequential beams, temperature influence during MRI acquisition and dose distribution integrity. Results: MAGIC-f depth dose measurements are compatible with the dosimetric table data within +/- 4% uncertainty. The dosimeter's R-2 response varies linearly with dose at least from 0 to 6 Gy. The time-course of the sensitivity of the dosimeter following irradiation, indicated stabilization after 2 weeks. The dosimeter's response to irradiation was altered by 6% when increasing the energy from cobalt beams to 10 MV beams. The dose rate dependence of this new formulation of gel dosimeter is small: less than 2.5% for a variation from 200 to 500 cGy/min, and the dependence with the fractionation scheme is about 50% smaller than for standard MAGIC gel, The dependence on scanning temperature was also verified, and the integrity of the dose distribution was confirmed for a period of 90 days. Conclusions: The results demonstrate the applicability of this new dosimeter in tridimensional dose distribution measurements. (C) 2012 Elsevier Ltd. All rights reserved.

Sympathetic overactivity precedes metabolic dysfunction in a fructose model of glucose intolerance in mice

De Angelis K, Senador DD, Mostarda C, Irigoyen MC, Morris M. Sympathetic overactivity precedes metabolic dysfunction in a fructose model of glucose intolerance in mice. Am J Physiol Regul Integr Comp Physiol 302: R950-R957, 2012. First published February 8, 2012; doi: 10.1152/ajpregu.00450.2011.-Consumption of high levels of fructose in humans and animals leads to metabolic and cardiovascular dysfunction. There are questions as to the role of the autonomic changes in the time course of fructose-induced dysfunction. C57/BL male mice were given tap water or fructose water (100 g/l) to drink for up to 2 mo. Groups were control (C), 15-day fructose (F15), and 60-day fructose (F60). Light-dark patterns of arterial pressure (AP) and heart rate (HR), and their respective variabilities were measured. Plasma glucose, lipids, insulin, leptin, resistin, adiponectin, and glucose tolerance were quantified. Fructose increased systolic AP (SAP) at 15 and 60 days during both light (F15: 123 +/- 2 and F60: 118 +/- 2 mmHg) and dark periods (F15: 136 +/- 4 and F60: 136 +/- 5 mmHg) compared with controls (light: 111 +/- 2 and dark: 117 +/- 2 mmHg). SAP variance (VAR) and the low-frequency component (LF) were increased in F15 (>60% and >80%) and F60 (>170% and >140%) compared with C. Cardiac sympatho-vagal balance was enhanced, while baroreflex function was attenuated in fructose groups. Metabolic parameters were unchanged in F15. However, F60 showed significant increases in plasma glucose (26%), cholesterol (44%), triglycerides (22%), insulin (95%), and leptin (63%), as well as glucose intolerance. LF of SAP was positively correlated with SAP. Plasma leptin was correlated with triglycerides, insulin, and glucose tolerance. Results show that increased sympathetic modulation of vessels and heart preceded metabolic dysfunction in fructose-consuming mice. Data suggest that changes in autonomic modulation may be an initiating mechanism underlying the cluster of symptoms associated with cardiometabolic disease.