Chronic hyperhomocysteinemia impairs vascular function in ovariectomized rat carotid arteries

Homocysteine is an independent risk factor for coronary heart disease, as well as for cerebrovascular and peripheral vascular diseases. The purpose of this study was to investigate the effects of hyperhomocysteinemia (HHcy) on vascular reactivity within carotid artery segments isolated from ovariectomized female rats. Treatment with dl-Hcy thiolactone (1 g/kg body weight per day) reduced the phenylephrine-induced contraction of denuded rings. However, the treatment did not alter KCl-induced contractions, or relaxations induced by sodium nitroprusside or acetylcholine. We report elevated expressions of iNOS, eNOS, and nitrotyrosine in homocysteine-treated rat artery sections. Moreover, the inhibition of NOS by l-NAME, 1,400 W, or l-NNA restored phenylephrine-induced vasoconstriction in carotid artery segments from Hcy-treated rats. In conclusion, our findings show that severe HHCy can promote an acute decrease in the endothelium-independent contractile responses of carotid arteries to adrenergic agonists. This effect was restored by nitric oxide synthase inhibitors, which further supports the involvement of nitric oxide in HHcy-derived vascular dysfunction.

In the eye of the storm: exploring the introduction of environmental issues in the production function in Brazilian companies

This article aims to analyse the introduction of environmental issues in the context of the production function, which has been referred to as the organisational area to lead corporate environmental management. With that purpose, the theoretical references for corporate environmental management and the necessary alterations in production function have been organised to include environmental aspects, especially in terms of product and process development, quality management, and logistics. Considering that this research field still lacks empirical evidence for Brazilian companies, four case studies were conducted using companies located in the country. The environmental management maturity level of those companies tends to follow the rate with which the environmental issue is introduced in production sub-areas, especially in the product development process. However, in most cases we found that the companies had difficulties in structuring the insertion of the environmental dimension in logistics. The final notes point out the distance observed between what is recommended by international literature and the reality of Brazilian companies in the challenge of making the production function environmentally friendly.

Developmental characterization, function and regulation of a Laccase2 encoding gene in the honey bee, Apis mellifera (Hymenoptera, Apinae)

In insects, exoskeleton (cuticle) formation at each molt cycle includes complex biochemical pathways wherein the laccase enzymes (EC 1.10.3.2) may have a key role. We identified an Amlac2 gene that encodes a laccase2 in the honey bee, Apis mellifera, and investigated its function in exoskeleton differentiation. The Amlac2 gene consists of nine exons resulting in an ORE of 2193 nucleotides. The deduced translation product is a 731 amino acid protein of 81.5 kDa and a pl of 6.05. Amlac2 is highly expressed in the integument of pharate adults, and the expression precedes the onset of cuticle pigmentation and the intensification of sclerotization. In accordance with the temporal sequence of exoskeleton differentiation from anterior to posterior direction, the levels of Amlac2 transcript increase earlier in the thoracic than in the abdominal integument. The gene expression lasts even after the bees emerge from brood cells and begin activities in the nest, but declines after the transition to foraging stage, suggesting that maturation of the exoskeleton is completed at this stage. Post-transcriptional knockdown of Amlac2 gene expression resulted in structural abnormalities in the exoskeleton and drastically affected adult eclosion. By setting a ligature between the thorax and abdomen of early pupae we could delay the increase in hemolymph ecdysteroid levels in the abdomen. This severely impaired the increase in Amlac2 transcript levels and also the differentiation of the abdominal exoskeleton. Taken together, these results indicate that Amlac2 expression is controlled by ecdysteroids and has a critical role in the differentiation of the adult exoskeleton of honey bees. (C) 2010 Elsevier Ltd. All rights reserved.

Microdialysis study of striatal dopamine in MPTP-hemilesioned rats challenged with apomorphine and amphetamine

Motor impairments of Parkinson`s disease (PD) appear only after the loss of more than 70% of the DAergic neurons of the substantia nigra pars compacta (SNc). An earlier phase of this disease can be modeled in rats that received a unilateral infusion of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) into the SNc. Though these animals do not present gross motor impairments, they rotate towards the lesioned side when challenged with DAergic drugs, like amphetamine and apomorphine. The present study aimed to test whether these effects occur because the drugs disrupt compensatory mechanisms that keep extracellular levels of dopamine in the striatum (DA(E)) unchanged. This hypothesis was tested by an in vivo microdialysis study in awake rats with two probes implanted in the right and left striatum. Undrugged rats did not present turning behaviour and their basal DA(E) did not differ between the lesioned and sham-lesioned sides. However, after apomorphine treatment, DA(E) decreased in both sides, but to a larger extent in the lesioned side at the time the animals started ipsiversive turning behaviour. After amphetamine challenge, DA(E) increased in both sides, becoming significantly higher in the non-lesioned side at the time the animals started ipsiversive turning behaviour. These results are in agreement with the hypothesis that absence of gross motor impairments in this rat model of early phase PD depends on maintenance of extracellular DA by mechanisms that may be disrupted by events demanding its alteration to higher or lower levels. (C) 2010 Elsevier B.V. All rights reserved.

GABAergic REGULATION OF AUDITORY SENSORY GATING IN LOW- AND HIGH-ANXIETY RATS SUBMITTED TO A FEAR CONDITIONING PROCEDURE

The inferior colliculus (IC) is primarily involved in the processing of acoustic stimuli, being in a position to send auditory information to motor centers that participate in behaviors such as prey catching and predators` avoidance The role of the central nucleus of the IC (CIC) on fear and anxiety has been suggested on the basis that rats are able to engage in tasks to decrease the aversiveness of CIC stimulation, increased Fos immunolabeling during diverse aversive states and increased CIC auditory evoked potentials (AEP) induced by conditioned fear stimuli Additionally it was shown that brainstem AEP, represented by wave V, for which the main generator is the IC, is increased during experimentally induced anxiety Rats segregated according to their low or high emotional reactivity have been used as an important tool in the study of fear and anxiety The IC contains a high density of GABA receptors Since the efficacy of an anxiolytic compound is a function of the animal`s anxiety level, it is possible that GABA-benzodiazepine (Bzp) agents affect LA and HA animals differently In this study we investigated the GABA-Bzp influence on the modulation of AEP in rats with low (LA) or high-anxiety (HA) levels, as assessed by the elevated plus maze test (EPM) GABA-Bzp modulation on the unconditioned AEP response was analyzed by using intra CIC injections (0 2 mu l) of the GABA-Bzp agonists muscimol (121 ng) and diazepam (30 mu g) or the GABA inhibitors bicuculline (10 ng) and semicarbazide (7 mu g) In a second experiment, we evaluate the effects of contextual aversive conditioning on AEP using foot shocks as unconditioned stimuli On the unconditioned fear paradigm GABA inhibition in creased AEP in LA rats and decreases this measure in HA counterparts Muscimol was effective in reducing AEP in both LA and HA rats Contextual fear stimuli increased the magnitude of AEP In spite of no effect obtained with diazepam in LA rats the drug inhibited AEP in HA animals The specificity of the regulatory mechanisms mediated by GABA Bzp for the ascending neurocircuits responsible for the acquisition of aversive information in LA and HA animals shed light on the processing of sensory information underlying the generation of defensive reactions (C) 2010 IBRO Published by Elsevier Ltd All rights reserved

RNAi-mediated silencing of vitellogenin gene function turns honeybee (Apis mellifera) workers into extremely precocious foragers

The switch from within-hive activities to foraging behavior is a major transition in the life cycle of a honeybee (Apis mellifera) worker. A prominent regulatory role in this switch has long been attributed to juvenile hormone (JH), but recent evidence also points to the yolk precursor protein vitellogenin as a major player in behavioral development. In the present study, we injected vitellogenin double-stranded RNA (dsVg) into newly emerged worker bees of Africanized genetic origin and introduced them together with controls into observation hives to record flight behavior. RNA interference-mediated silencing of vitellogenin gene function shifted the onset of long-duration flights (> 10 min) to earlier in life (by 3-4 days) when compared with sham and untreated control bees. In fact, dsVg bees were observed conducting such flights extremely precociously, when only 3 days old. Short-duration flights (< 10 min), which bees usually perform for orientation and cleaning, were not affected. Additionally, we found that the JH titer in dsVg bees collected after 7 days was not significantly different from the controls. The finding that depletion of the vitellogenin titer can drive young bees to become extremely precocious foragers could imply that vitellogenin is the primary switch signal. At this young age, downregulation of vitellogenin gene activity apparently had little effect on the JH titer. As this unexpected finding stands in contrast with previous results on the vitellogenin/JH interaction at a later age, when bees normally become foragers, we propose a three-step sequence in the constellation of physiological parameters underlying behavioral development.

Charcot`s arthropathy secondary to herpetic encephalitis sequelae: an unusual presentation

Neuropathic arthropathy (Charcot`s arthropathy) is a progressive articular disease associated with a reduced sensorial and protector proprioceptive reflex. Its etiology includes many different conditions such as syringomyelia, traumatic lesion causing medullary deformity, spina bifida, diabetic neuropathy, leprosy neuropathy, neurofibromatosis, amyloid neuropathy, alcohol, and repetitive injection of hydrocortisone into joints, among others. However, the relationship between Charcot`s arthropathy and herpetic encephalitis has not yet been described. Herpes encephalitis causes acute and chronic diseases of the peripheral or central nervous system. It can manifest as subacute encephalitis, recurrent meningitis, or myelitis. It can also resemble psychiatric syndromes, diplopia, sensory changes in the face and limbs, personality changes, frontal dysexecutive syndrome, stiff neck, subclinical alterations of the vestibular function, intracranial hypertension, convulsion, hemiparesis, and generally includes motor components, among others. On the other hand, pure peripheral sensory disturbance has not been described. In this article, we report the clinical case of a patient with Charcot`s arthropathy secondary to pure peripheral sensory polyneuropathy as a consequence of progressive herpetic encephalitis sequelae. In this article, the authors report the first case of Charcot`s arthropathy secondary to herpetic encephalitis.

Improvement in Insulin Sensitivity and B-Cell Function Following Ileal Interposition with Sleeve Gastrectomy in Type 2 Diabetic Patients: Potential Mechanisms

Bariatric surgery in morbidly obese type 2 diabetic (T2DM) patients is associated with high rates of diabetes remission. We investigated the mechanisms of the anti-diabetic effect of the laparoscopic ileal interposition with sleeve gastrectomy (LII-SG) in normal weight (NW), overweight (OW) and obese (OB) T2DM patients. Ninety-four patients (aged 54 +/- 8 years) with long-standing (median 10 years), treated diabetes (median HbA(1c) = 8.6%), who were NW (15), OW (64) or OB (15) based on BMI, underwent LII-SG. Insulin sensitivity and parameters of -cell function were measured from an Oral Glycaemic Tolerance Test pre- and post-operatively. At a median of 13.4 months post-operatively, weight loss averaged 9.4 +/- 1.3, 16.8 +/- 0.8 and 23.2 +/- 1.7 kg in NW, OW and OB subjects, respectively (p < 0.0001). Insulin sensitivity was fully restored (395 [108] vs 208 [99] ml min(-1) m(-2)), fasting insulin secretion rate decreased (68 [52] vs 146 [120] pmol min(-1) m(-2)) and total insulin output increased (52 [26] vs 39 [28] nmol m(-2), all p a parts per thousand currency signaEuro parts per thousand 0.001). -cell glucose sensitivity doubled (37 [33] vs 18 [24] mol min(-1) m(-2) mM(-1), p < 0.0001). The only parameter predicting remission of diabetes was a lower baseline insulin sensitivity (p = 0.005). LII-SG induced changes on T2DM by mechanisms in part distinct from weight loss, principally involving restoration of insulin sensitivity and improvement of -cell function.

Wavefront analysis and modulation transfer function of three multifocal intraocular lenses

Purpose: To evaluate wavefront performance and modulation transfer function (MTF) in the human eye aft er the implantation of diffractive or refractive multifocal intraocular lenses (IOLs). Materials and Methods: This was a prospective, interventional, comparative, nonrandomized clinical study. Uncorrected distance and near visual acuity, and wavefront analysis including MTF curves (iTrace aberrometer, Tracey Technologies, Houston, TX, USA) were measured in 60 patients aft er bilateral IOL implantation with 6 months of follow-up. Forty eyes received the diffractive ReSTOR (Alcon), 40 eyes received the refractive ReZoom (Advanced Medical Optics) and 40 eyes, the Tecnis ZM900 (Advanced Medical Optics). The comparison of MTF and aberration between the intraocular lenses was performed using analysis of variance (ANOVA), followed by the Dunn test when necessary. Results: The mean uncorrected distance visual acuity was similar in all three groups of multifocal IOLs. The ReSTOR group provided better uncorrected near visual acuity than the ReZoom group (P < 0.001), but similar to the Tecnis group. Spherical aberration was significantly higher in the ReZoom group (P = 0.007). Similar MTF curves were found for the aspheric multifocal IOL Tecnis and the spheric multifocal IOL ReSTOR, and both performed better than the multifocal IOL ReZoom in a 5 mm pupil (P < 0.001 at all spatial frequencies). Conclusions: Diffractive IOLs studied presented similar MTF curves for a 5 mm pupil diameter. Both diffractive IOLs showed similar spherical aberration, which was significantly better with the full-diffractive IOL Tecnis than with the refractive IOL ReZoom.

Prolonged recruitment manoeuvre improves lung function with less ultrastructural damage in experimental mild acute lung injury

The effects of prolonged recruitment manoeuvre (PRM) were compared with sustained inflation (SI) in paraquat-induced mild acute lung injury (ALI) in rats. Twenty-four hours after ALI induction, rats were anesthetized and mechanically ventilated with VT = 6 ml/kg and positive end-expiratory pressure (PEEP) = 5 cmH(2)O for 1 h. SI was performed with an instantaneous pressure increase of 40 cmH(2)O that was sustained for 40 s, while PRM was done by a step-wise increase in positive inspiratory pressure (PIP) of 15-20-25 cmH(2)O above a PEEP of 15 cm H(2)O (maximal PIP = 40 cmH(2)O), with interposed periods of PIP = 10 cmH(2)O above a PEEP = 15 cmH(2)O. Lung static elastance and the amount of alveolar collapse were more reduced with PRM than SI, yielding improved oxygenation. Additionally, tumour necrosis factor-alpha, interleukin-6, interferon-gamma, and type III procollagen mRNA expressions in lung tissue and lung epithelial cell apoptosis decreased more in PRM. In conclusion, PRM improved lung function, with less damage to alveolar epithelium, resulting in reduced pulmonary injury. (C) 2009 Elsevier BLV. All rights reserved.

Functional mapping of the motor cortex of the rat using transdural electrical stimulation

Motor cortex stimulation oriented by functional cortical mapping is used mainly for treating otherwise intractable neurological disorders, however. its mechanism of action remains elusive. Herein, we present a new method for functional mapping of the rat motor cortex using non-invasive transdural electrical stimulation. This method allows a non-invasive mapping of the surface of the neocortex providing a differentiation of representative motor areas. This Study may facilitate further investigation about the mechanisms mediating the effects of electrical stimulation, possibly benefiting patients who do not respond to this neuromodulation therapy. (c) 2009 Elsevier B.V. All rights reserved.

Cardiac resynchronization therapy evaluated by myocardial scintigraphy with (99m)Tc-MIBI: changes in left ventricular uptake, dyssynchrony, and function

(99m)Tc-MIBI gated myocardial scintigraphy (GMS) evaluates myocyte integrity and perfusion, left ventricular (LV) dyssynchrony and function. Cardiac resynchronization therapy (CRT) may improve the clinical symptoms of heart failure (HF), but its benefits for LV function are less pronounced. We assessed whether changes in myocardial (99m)Tc-MIBI uptake after CRT are related to improvement in clinical symptoms, LV synchrony and performance, and whether GMS adds information for patient selection for CRT. A group of 30 patients with severe HF were prospectively studied before and 3 months after CRT. Variables analysed were HF functional class, QRS duration, LV ejection fraction (LVEF) by echocardiography, myocardial (99m)Tc-MIBI uptake, LV end-diastolic volume (EDV) and end-systolic volume (ESV), phase analysis LV dyssynchrony indices, and regional motion by GMS. After CRT, patients were divided into two groups according to improvement in LVEF: group 1 (12 patients) with increase in LVEF of 5 or more points, and group 2 (18 patients) without a significant increase. After CRT, both groups showed a significant improvement in HF functional class, reduced QRS width and increased septal wall (99m)Tc-MIBI uptake. Only group 1 showed favourable changes in EDV, ESV, LV dyssynchrony indices, and regional motion. Before CRT, EDV, and ESV were lower in group 1 than in group 2. Anterior and inferior wall (99m)Tc-MIBI uptakes were higher in group 1 than in group 2 (p < 0.05). EDV was the only independent predictor of an increase in LVEF (p=0.01). The optimal EDV cut-off point was 315 ml (sensitivity 89%, specificity 94%). The evaluation of EDV by GMS added information on patient selection for CRT. After CRT, LVEF increase occurred in hearts less dilated and with more normal (99m)Tc-MIBI uptake.

Left Atrial Function After Ablation for Paroxysmal Atrial Fibrillation

Radiofirequency ablation of the pulmonary veins has been used to treat patients with paroxysmal atrial fibrillation (AF), and atrial damage after ablation is an issue of concern. To evaluate left atrial function shortly and midterm after ablation, 33 consecutive patients with paroxysmal AF were studied at baseline, 24 hours, and >= 6 months after ablation. Patients in sinus rhythm with normal ventricular function were included in the study. Echocardiographic measurements of left atrial volumes (Simpson`s rule) and transmitral and tissue Doppler myocardial (A`) velocities at the septal and lateral mitral annulus were undertaken at each time. Left atrial emptying fraction (EF; maximal - minimal left atrial volume/maximal left atrial volume) was used to express left atrial function. After 8 +/- 2 months, 30 of 33 patients returned (23 men, age 53 +/- 13 years), and all except 2 were in sinus rhythm. Shortly after ablation, left atrial minimal volumes increased (from 30 +/- 15 to 35 +/- 15 ml; p = 0.02), with maximal volumes unchanged, resulting in decreased left atrial EF (from 47 +/- 8 to 40 +/- 7 ml; p <0.05). Tissue Doppler septal A` velocities also decreased (from 8.2 +/- 1.8 to 6.9 +/- 2.0 cm/s; p <0.05). However, after midterm follow-up, both left atrial EF and septal A` velocities had slightly increased compared with shortly after ablation, although left atrial volumes remained similar to baseline. Septal A` velocity changes paralleled left atrial EF both shortly (r = 0.46, p = 0.02) and at midterm after ablation (r = 0.47, p = 0.01). In conclusion, after radiofrequency ablation, patients with paroxysmal AF experienced an initial impairment in atrial function, with improvement at longer term follow-up. (C) 2009 Elsevier Inc. All rights reserved. (Am J Cardiol 2009;103: 395-398)

Antinociception induced by epidural motor cortex stimulation in naive conscious rats is mediated by the opioid system

Epidural motor cortex stimulation (MCS) has been used for treating patients with neuropathic pain resistant to other therapeutic approaches. Experimental evidence suggests that the motor cortex is also involved in the modulation of normal nociceptive response, but the underlying mechanisms of pain control have not been clarified yet. The aim of this study was to investigate the effects of epidural electrical MCS on the nociceptive threshold of naive rats. Electrodes were placed on epidural motor cortex, over the hind paw area, according to the functional mapping accomplished in this study. Nociceptive threshold and general activity were evaluated under 15-min electrical stimulating sessions. When rats were evaluated by the paw pressure test, MCS induced selective antinociception in the paw contralateral to the stimulated cortex, but no changes were noticed in the ipsilateral paw. When the nociceptive test was repeated 15 min after cessation of electrical stimulation, the nociceptive threshold returned to basal levels. On the other hand, no changes in the nociceptive threshold were observed in rats evaluated by the tail-flick test. Additionally, no behavioral or motor impairment were noticed in the course of stimulation session at the open-field test. Stimulation of posterior parietal or somatosensory cortices did not elicit any changes in the general activity or nociceptive response. Opioid receptors blockade by naloxone abolished the increase in nociceptive threshold induced by MCS. Data shown herein demonstrate that epidural electrical MCS elicits a substantial and selective antinociceptive effect, which is mediated by opioids. (C) 2008 Elsevier B.V. All rights reserved.

Idiopathic spinal epidural hematoma in patients with sudden paraplegia: A case report

Introduction. Spontaneous spinal epidural hematoma (SEH) represents 0.3-0.9% of spinal epidural space-occupying lesions, and most surgeons advocate aggressive and early surgical intervention. In. this paper we describe a patient with SEH with sudden paraplegia. Case report. This 30-year-old man had experienced one prior episode of sudden dorsal pain two days before the current admission and while he waited medical attendance, his legs suddenly became weak, and immediately afterwards, he became completely paraplegic in minutes. The patient had complete paraplegia, analgesia below the T4 level and urinary retention. He had no anticoagulant agent and no coagulopathic disease. He was submitted to computerized tomography that demonstrated a dorsally located epidural hematoma extending from the T3 to the T6 level with spinal cord compression. A laminectomy from T3 to T7 was performed four hours after the onset of the symptom. In postoperative time the patient presented the partial sensorial recovery and motor force grade II. The patient was directed to a neurorehabilitation program and in the last medical evaluation he presented recovery for motor grade III-IV without pain. Conclusion. The SHE is rare, with severe neurological consequences for patients and early surgical treatment persist as essential for motor recovery.