Optimal design of 3R manipulators by using classical techniques and simulated annealin

In this paper, the optimum design of 3R manipulators is formulated and solved by using an algebraic formulation of workspace boundary. A manipulator design can be approached as a problem of optimization, in which the objective functions are the size of the manipulator and workspace volume; and the constrains can be given as a prescribed workspace volume. The numerical solution of the optimization problem is investigated by using two different numerical techniques, namely, sequential quadratic programming and simulated annealing. Numerical examples illustrate a design procedure and show the efficiency of the proposed algorithms.

Response threshold to aversive stimuli in stimulated early protein-malnourished rats

Two animal models of pain were used to study the effects of short-term protein malnutrition and environmental stimulation on the response threshold to aversive stimuli. Eighty male Wistar rats were used. Half of the pups were submitted to malnutrition by feeding their mothers a 6% protein diet from 0 to 21 days of age while the mothers of the other half (controls) were well nourished, receiving 16% protein. From 22 to 70 days all rats were fed commercial lab chow. Half of the animals in the malnourished and control groups were maintained under stimulating conditions, including a 3-min daily handling from 0 to 70 days and an enriched living cage after weaning. The other half was reared in a standard living cage. At 70 days, independent groups of rats were exposed to the shock threshold or to the tail-flick test. The results showed lower body and brain weights in malnourished rats when compared with controls at weaning and testing. In the shock threshold test the malnourished animals were more sensitive to electric shock and environmental stimulation increased the shock threshold. No differences due to diet or environmental stimulation were found in the tail-flick procedure. These results demonstrate that protein malnutrition imposed only during the lactation period is efficient in inducing hyperreactivity to electric shock and that environmental stimulation attenuates the differences in shock threshold produced by protein malnutrition

Paradoxical increase of exploratory behavior in the elevated plus-maze by rats exposed to two kinds of aversive stimuli

Albino rats were submitted to a 24-h period of social isolation (individual housing) combined with 0, 1, 2 or 3 twenty-four-hour periods of exposure to different vivaria (novelty) and tested in the elevated plus-maze. Results, reported as mean ± SEM for N = 12, show that the time (in seconds) spent in the open arms by rats exposed to novelty for 0, 1, 2 and 3 days was 28.3 ± 4.4, 31.6 ± 3.2, 29.1 ± 3.5 and 25.0 ± 3.3, respectively, when grouped in the same vivarium; 29.6 ± 2.7, 7.6 ± 2.1, 9.6 ± 4.4 and 28.5 ± 3.7 when grouped in different vivaria; 2.9 ± 1.1, 1.8 ± 1.0, 2.7 ± 1.1 and 0 ± 0 when isolated in the same vivarium, and 2.6 ± 1.1, 31.5 ± 8.2, 24.8 ± 4.2 and 0 ± 0 when isolated in different vivaria. The number of entries into the open and closed arms followed a similar trend. This indicates that, separately, both exposure to novelty and isolation are aversive manipulations. Paradoxically, when novelty was combined with a concomitant 24-h period of social isolation prior to testing, the decrease in exploratory behavior caused by either of the two aversive manipulations alone was reverted. These results are indicative that less intense anxiety triggers mechanisms mediating less energetic behavior such as freezing, while higher levels trigger mechanisms mediating more vigorous action, such as flight/fight behavior, since the combination of two aversive situations resulted in more exploratory behavior than with either alone. They are also suggestive of habituation to the effects of novelty, since exposure to it for 3 days produced exploratory behavior similar to that of controls

Aversive stimulation during the stress-hyporesponsive period does not affect the number of corticotroph cells in neonatal male rats

Immunohistochemistry was used to evaluate the effects of neonatal handling and aversive stimulation during the first 10 days of life on the number of corticotrophs in the anterior lobe of the pituitary of 11-day-old male Wistar rats. Since adult rats handled during infancy respond with reduced corticosterone secretion in response to stressors and with less behavior inhibition in novel environments, we assumed that neonatal stimulation could affect pituitary morphology during this critical period of cell differentiation. Three groups of animals were studied: intact (no manipulation, N = 5), handled (N = 5) and stimulated (submitted to 3 different aversive stimuli, N = 5). The percentage of ACTH-immunoreactive cells in the anterior lobe of the pituitary (number of ACTH-stained cells divided by total number of cells) was determined by examining three slices per pituitary in which a minimum of 200 cells were counted by two independent researchers. Although animals during the neonatal period are less reactive to stress-like stimulation in terms of ACTH and corticosterone secretion, results showed that the relative number of ACTH-stained cells of neonatal handled (0.25 ± 0.01) and aversive stimulated (0.29 ± 0.03) rats was not significantly different from intact (0.30 ± 0.03) animals. Neonatal stimulation may have a differential effect on the various subpopulations of corticotroph cells in the anterior pituitary

Involvement of dopamine receptors in diethylpropion-induced conditioning place preference

Diethylpropion (DEP) is an amphetamine-like agent used as an anorectic drug. Abuse of DEP has been reported and some restrictions of its use have been recently imposed. The conditioning place preference (CPP) paradigm was used to evaluate the reinforcing properties of DEP in adult male Wistar rats. After initial preferences were determined, animals weighing 250-300 g (N = 7 per group) were conditioned with DEP (10, 15 or 20 mg/kg). Only the dose of 15 mg/kg produced a significant place preference (358 ± 39 vs 565 ± 48 s). Pretreatment with the D1 antagonist SCH 23390 (0.05 mg/kg, sc) 10 min before DEP (15 mg/kg, ip) blocked DEP-induced CPP (418 ± 37 vs 389 ± 31 s) while haloperidol (0.5 mg/kg, ip), a D2 antagonist, 15 min before DEP was ineffective in modifying place conditioning produced by DEP (385 ± 36 vs 536 ± 41 s). These results suggest that dopamine D1 receptors mediate the reinforcing effect of DEP

Persistent attenuation and enhancement of the earthworm main muscle contraction generator response induced by repeated stimulation of a peripheral neuron

Responses evoked in the earthworm, Amynthas hawayanus, main muscle contraction generator M-2 (postsynaptic mechanical-stimulus-sensitive) neuron by threshold mechanical stimuli in 2-s intertrial intervals (ITI) were used as the control or unconditioned responses (UR). Their attenuation induced by decreasing these intervals in non-associative conditioning and their enhancement induced by associating the unconditioned stimuli (US) to a train of short (0.1 s) hyperpolarizing electrical substitutive conditioning stimuli (SCS) in the Peri-Kästchen (PK) neuron were measured in four parameters, i.e., peak numbers (N) and amplitude ()averaged from 120 responses, sum of these amplitudes (SAMP) and the highest peak amplitude (V) over a period of 4 min. Persistent attenuation similar to habituation was induced by decreasing the control ITI to 0.5 s and 2.0 s in non-associative conditioning within less than 4 min. Dishabituation was induced by randomly pairing one of these habituated US to an electrical stimulus in the PK neuron. All four parameters of the UR were enhanced by forward (SCS-US), but not backward (US-SCS), association of the US with 25, 100 and 250-Hz trains of SCS with 40-ms interstimulus intervals (ISI) for 4 min and persisted for another 4 min after turning off the SCS. The enhancement of these parameters was proportional to the SCS frequencies in the train. No UR was evoked by the SCS when the US was turned off after 4 min of classical conditioning.

Involvement of hippocampal NMDA receptors in retention of shuttle avoidance conditioning in rats

The purpose of this research was to evaluate the role of hippocampal N-methyl-D-aspartate (NMDA) receptors in acquisition and consolidation of memory during shuttle avoidance conditioning in rats. Adult male Wistar rats were surgically implanted with cannulae aimed at the CA1 area of the dorsal hippocampus. After recovery from surgery, animals were trained and tested in a shuttle avoidance apparatus (30 trials, 0.5-mA footshock, 24-h training-test interval). Immediately before or immediately after training, animals received a bilateral intrahippocampal 0.5-µl infusion containing 5.0 µg of the NMDA competitive receptor antagonist aminophosphonopentanoic acid (AP5) or vehicle (phosphate-buffered saline, pH 7.4). Infusion duration was 2 min per side. Pre-training infusion of AP5 impaired retention test performance (mean ± SEM number of conditioned responses (CRs) during retention test session was 16.47 ± 1.78 in the vehicle group and 9.93 ± 1.59 in the AP5 group; P<0.05). Post-training infusion of AP5 did not affect retention (mean ± SEM number of conditioned responses during retention test session was 18.46 ± 1.94 in the vehicle group and 20.42 ± 2.38 in the AP5 group; P>0.10). This impairment could not be attributed to an effect on acquisition, motor activity or footshock sensitivity since AP5 affected neither training session performance measured by the number of CRs nor the number of intertrial crossings during the training session. These data suggest that NMDA receptors in the hippocampus are critical for retention of shuttle avoidance conditioning, in agreement with previous evidence showing a role of NMDA receptors in fear memory.

The brain decade in debate: VI. Sensory and motor maps: dynamics and plasticity

This article is an edited transcription of a virtual symposium promoted by the Brazilian Society of Neuroscience and Behavior (SBNeC). Although the dynamics of sensory and motor representations have been one of the most studied features of the central nervous system, the actual mechanisms of brain plasticity that underlie the dynamic nature of sensory and motor maps are not entirely unraveled. Our discussion began with the notion that the processing of sensory information depends on many different cortical areas. Some of them are arranged topographically and others have non-topographic (analytical) properties. Besides a sensory component, every cortical area has an efferent output that can be mapped and can influence motor behavior. Although new behaviors might be related to modifications of the sensory or motor representations in a given cortical area, they can also be the result of the acquired ability to make new associations between specific sensory cues and certain movements, a type of learning known as conditioning motor learning. Many types of learning are directly related to the emotional or cognitive context in which a new behavior is acquired. This has been demonstrated by paradigms in which the receptive field properties of cortical neurons are modified when an animal is engaged in a given discrimination task or when a triggering feature is paired with an aversive stimulus. The role of the cholinergic input from the nucleus basalis to the neocortex was also highlighted as one important component of the circuits responsible for the context-dependent changes that can be induced in cortical maps.

Role of the cardiac nerve in the adaptive changes of heart rate in response to an aversive stimulus in Megalobulimus mogianensis

The effect of an aversive stimulus represented by contact with a hot plate on the heart rate of Megalobulimus mogianensis was evaluated with electrocardiogram recording in intact snails (N = 8). All stimulated animals showed an increase in heart rate, with mean values ranging from 35.6 ± 1.2 (basal heart rate) to 43.8 ± 0.9 bpm (post-stimulation heart rate). The cardioacceleration was followed by gradual recovery of the basal heart rate, with mean recovery times varying from 4.3 ± 0.3 to 5.8 ± 0.6 min. Repetition of the stimulus did not affect the magnitude of variation nor did it influence the basal heart rate recovery time. To investigate the role of the cardiac nerve in mediating the heart rate alterations induced by the aversive stimulus, denervated (N = 8) and sham-operated (N = 8) animals were also tested. Although the aversive stimulus caused the heart rate to increase significantly in both experimental groups, the mean increase in heart rate in denervated animals (4.4 ± 0.4 bpm) was 57% of the value obtained in sham-operated animals (7.7 ± 1.3 bpm), indicating that the cardiac nerve is responsible for 43% of the cardioacceleration induced by the aversive stimulus. The cardioacceleration observed in denervated snails may be due to an increase in venous return promoted by the intense muscular activity associated with the withdrawal response. Humoral factors may also be involved. A probable delaying inhibitory effect of the cardiac nerve on the recuperation of the basal heart rate is suggested.

A retrospective comparison of cyclophosphamide plus antithymocyte globulin with cyclophosphamide plus busulfan as the conditioning regimen for severe aplastic anemia

Allogeneic hematopoietic stem cell transplantation (AHSCT) is the treatment of choice for young patients with severe aplastic anemia (SAA). The association of antithymocyte globulin (ATG) and cyclophosphamide (CY) is the most frequently used conditioning regimen for this disease. We performed this retrospective study in order to compare the outcomes of HLA-matched sibling donor AHSCT in 41 patients with SAA receiving cyclophosphamide plus ATG (ATG-CY, N = 17) or cyclophosphamide plus busulfan (BU-CY, N = 24). The substitution of BU for ATG was motivated by the high cost of ATG. There were no differences in the clinical features between the two groups, including age, gender, cytomegalovirus status, ABO match, interval between diagnosis and transplant, and number of total nucleated cells infused. No differences were observed in the time to neutrophil and platelet engraftment, or in the risk of veno-occlusive disease and hemorrhage. However, there was a higher risk of mucositis in the BU-CY group (71 vs 24%, P = 0.004). There were no differences in the incidence of neutrophil and platelet engraftment, acute and chronic graft-versus-host disease, and transplant-related mortality. There was a higher incidence of late rejection in the ATG-CY group (41 vs 4%, P = 0.009). Although the ATG-CY group had a longer follow-up (101 months) than the BU-CY group (67 months, P = 0.04), overall survival was similar between the groups (69 vs 58%, respectively, P = 0.32). We conclude that the association BU-CY is a feasible option to the conventional ATG-CY regimen in this population.

Ischemic post-conditioning attenuates the intestinal injury induced by limb ischemia/reperfusion in rats

The purpose of this study was to investigate the protective effects of ischemic post-conditioning on damage to the barrier function of the small intestine caused by limb ischemia-reperfusion injury. Male Wistar rats were randomly divided into 3 groups (N = 36 each): sham operated (group S), lower limb ischemia-reperfusion (group LIR), and post-conditioning (group PC). Each group was divided into subgroups (N = 6) according to reperfusion time: immediate (0 h; T1), 1 h (T2), 3 h (T3), 6 h (T4), 12 h (T5), and 24 h (T6). In the PC group, 3 cycles of reperfusion followed by ischemia (each lasting 30 s) were applied immediately. At all reperfusion times (T1-T6), diamine oxidase (DAO), superoxide dismutase (SOD), and myeloperoxidase (MPO) activity, malondialdehyde (MDA) intestinal tissue concentrations, plasma endotoxin concentrations, and serum DAO, tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) concentrations were measured in sacrificed rats. Chiu’s pathology scores for small intestinal mucosa were determined under a light microscope and showed that damage to the small intestinal mucosa was lower in group PC than in group LIR. In group PC, tissue DAO and SOD concentrations at T2 to T6, and IL-10 concentrations at T2 to T5 were higher than in group LIR (P < 0.05); however, tissue MPO and MDA concentrations, and serum DAO and plasma endotoxin concentrations at T2 to T6, as well as TNF-α at T2 and T4 decreased significantly (P < 0.05). These results show that ischemic post-conditioning attenuated the permeability of the small intestines after limb ischemia-reperfusion injury. The protective mechanism of ischemic post-conditioning may be related to inhibition of oxygen free radicals and inflammatory cytokines that cause organ damage.

What ethologically based models have taught us about the neural systems underlying fear and anxiety

Classical Pavlovian fear conditioning to painful stimuli has provided the generally accepted view of a core system centered in the central amygdala to organize fear responses. Ethologically based models using other sources of threat likely to be expected in a natural environment, such as predators or aggressive dominant conspecifics, have challenged this concept of a unitary core circuit for fear processing. We discuss here what the ethologically based models have told us about the neural systems organizing fear responses. We explored the concept that parallel paths process different classes of threats, and that these different paths influence distinct regions in the periaqueductal gray - a critical element for the organization of all kinds of fear responses. Despite this parallel processing of different kinds of threats, we have discussed an interesting emerging view that common cortical-hippocampal-amygdalar paths seem to be engaged in fear conditioning to painful stimuli, to predators and, perhaps, to aggressive dominant conspecifics as well. Overall, the aim of this review is to bring into focus a more global and comprehensive view of the systems organizing fear responses.

Fine-tuning of defensive behaviors in the dorsal periaqueductal gray by atypical neurotransmitters

This paper presents an up-to-date review of the evidence indicating that atypical neurotransmitters such as nitric oxide (NO) and endocannabinoids (eCBs) play an important role in the regulation of aversive responses in the periaqueductal gray (PAG). Among the results supporting this role, several studies have shown that inhibitors of neuronal NO synthase or cannabinoid receptor type 1 (CB1) receptor agonists cause clear anxiolytic responses when injected into this region. The nitrergic and eCB systems can regulate the activity of classical neurotransmitters such as glutamate and γ-aminobutyric acid (GABA) that control PAG activity. We propose that they exert a ‘fine-tuning’ regulatory control of defensive responses in this area. This control, however, is probably complex, which may explain the usually bell-shaped dose-response curves observed with drugs that act on NO- or CB1-mediated neurotransmission. Even if the mechanisms responsible for this complex interaction are still poorly understood, they are beginning to be recognized. For example, activation of transient receptor potential vanilloid type-1 channel (TRPV1) receptors by anandamide seems to counteract the anxiolytic effects induced by CB1 receptor activation caused by this compound. Further studies, however, are needed to identify other mechanisms responsible for this fine-tuning effect.

Classical and recent advances in the treatment of inflammatory bowel diseases

Crohn's disease (CD) and ulcerative colitis (UC) are intestinal disorders that comprise the inflammatory bowel diseases (IBD). These disorders have a significant effect on the quality of life of affected patients and the increasing number of IBD cases worldwide is a growing concern. Because of the overall burden of IBD and its multifactorial etiology, efforts have been made to improve the medical management of these inflammatory conditions. The classical therapeutic strategies aim to control the exacerbated host immune response with aminosalicylates, antibiotics, corticosteroids, thiopurines, methotrexate and anti-tumor necrosis factor (TNF) biological agents. Although successful in the treatment of several CD or UC conditions, these drugs have limited effectiveness, and variable responses may culminate in unpredictable outcomes. The ideal therapy should reduce inflammation without inducing immunosuppression, and remains a challenge to health care personnel. Recently, a number of additional approaches to IBD therapy, such as new target molecules for biological agents and cellular therapy, have shown promising results. A deeper understanding of IBD pathogenesis and the availability of novel therapies are needed to improve therapeutic success. This review describes the overall key features of therapies currently employed in clinical practice as well as novel and future alternative IBD treatment methods.

Influence of disinfestation and osmotic conditioning on the germinating behavior of australian royal palm (Archontophoenix alexandrae)seeds

The technique of Osmotic Conditioning, which consists of partial and controlled hydration of the seeds, has obtained success with various species of seeds, increasing the germinating span and tolerance to the adverse conditions of the environment, and has also reduced the time elapsed between sowing and the emergence of the plants. Associated to ideal storage conditions, the treatment has increased the performance of the seeds of tropical wood species. Aiming at studying the germinating environment and the effect of osmotic conditioning on the germination of seeds of the Australian Royal Palm tree, two experiments were performed. The first one evaluated the effect of disinfestation of the seeds of the Australian Royal Palm tree with NaClO. The treatments applied were: 0.5% sodium hypochlorite, exposure periods of 5, 15, 30, 45, 60, 90, 120 and 240 minutes, and the fungicide Captan, as control. The treatments with NaClO did not differ in relation to the final percentage of germination and to the germination speed index, and did not differ from the treatment control. The second test evaluated solutions with the following osmotic potentials: 0.0MPa (pure water), -0.4MPa, -0.6MPa and -0.8MPa, exposed for the periods of 10 and 20 days. The final percentage of germination did not differ among the treatments. The seeds hydrated in pure water for a period of 20 days showed a germination speed index significantly superior to the other treatments, and they did not show significant differences among themselves.