Proprioceptive neuromuscular facilitation in HTLV-I-associated myelopathy/tropical spastic paraparesis

Introduction: Human T cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) can impact the independence and motricity of patients. The aims of this study were to estimate the effects of physiotherapy on the functionality of patients with HAM/TSP during the stable phase of the disease using proprioceptive neuromuscular facilitation (PNF) and to compare two methods of treatment delivery. Methods: Fourteen patients with human T cell lymphotropic virus type I (HTLV-I) were randomly allocated into two groups. In group I (seven patients), PNF was applied by the therapist, facilitating the functional activities of rolling, sitting and standing, walking and climbing and descending stairs. In group II (seven patients), PNF was self-administered using an elastic tube, and the same activities were facilitated. Experiments were conducted for 1h twice per week for 12 weeks. Low-back pain, a modified Ashworth scale, the functional independence measure (FIM) and the timed up and go test (TUG) were assessed before and after the interventions. Results: In the within-group evaluation, low-back pain was significantly reduced in both groups, the FIM improved in group II, and the results of the TUG improved in group I. In the inter-group analysis, only the tone was lower in group II than in group I. Conclusions: Both PNF protocols were effective in treating patients with HAM/TSP.

Apparent competition through facilitation between Melanoides tuberculata and Biomphalaria glabrata and the control of schistosomiasis

Interactions between two species that result in reduced growth rates for both and extinction of one of the species are generally considered cases of asymmetric interspecific competition. Exploitative or interference competition is the usual mechanism invoked. Here we describe another mechanism producing the same result, named apparent competition through facilitation (ACF), observed between Melanoides tuberculata and Biomphalaria glabrata populations. The superior competitor actually gives some benefit to the other species, whose population becomes unstable with progressively increasing oscillations, leading to extinction. A model of ACF using difference equations suggests initial dynamics distinct from traditional interspecific competition. The dynamics of two freshwater snails in the field and in laboratory experiments suggest ACF, and these relations should be considered in studies of schistosomiasis control. ACF could occur in natural populations, but might have gone undetected because the final result is similar to traditional interspecific competition.

Facilitation of the main generator source of earthworm muscle contraction by a peripheral neuron

A constant facilitation of responses evoked in the earthworm muscle contraction generator neurons by responses evoked in the neurons of its peripheral nervous system was demonstrated. It is based on the proposal that these two responses are bifurcations of an afferent response evoked by the same peripheral mechanical stimulus but converging again on this central neuron. A single-peaked generator response without facilitation was demonstrated by sectioning the afferent route of the peripheral facilitatory modulatory response, or conditioning response (CR). The multipeaked response could be restored by restimulating the sectioned modulatory neuron with an intracellular substitutive conditioning stimulus (SCS). These multi-peaked responses were proposed to be the result of reverberating the original single peaked unconditioned response (UR) through a parallel (P) neuronal circuit which receives the facilitation of the peripheral modulatory neuron. This peripheral modulatory neuron was named "Peri-Kästchen" (PK) neuron because it has about 20 peripheral processes distributed on the surface of a Kästchen of longitudinal muscle cells on the body wall of this preparation as revealed by the Lucifer Yellow-CH-filling method.

Interactions between carpenter bees and orchid bees (Hymenoptera: Apidae) in flowers of Bertholletia excelsa Bonpl. (Lecythidaceae)

Competition between two species of bees for the same type of floral resource may generate antagonistic behavior between them, especially in cultivated areas where food resources are limited, seasonally and locally. In this study, was tested the hypothesis of antagonism between two solitary bee species of the family Apidae, Eulaema mocsaryi (Euglossini) and Xylocopa frontalis (Xylocopini), visiting the Brazil nut flowers (Bertholletia excelsa: Lecythidaceae) in a central Amazonia agricultural area. The visitation time was analyzed to detect the possible temporal overlap in the foraging of these bees. Furthermore, was analyzed their interspecific interactions for manipulating flower species visited by an opponent species, as well as attempts to attack this opponent. The individuals of Xylocopa frontalis visited the Brazil nut flowers before Eulaema mocsaryi, although the peak visitation of both did not presented significant differences. Neither of the species manipulated flowers recently visited by opponent species, and there were practically no antagonistic interactions between them. Thus, X. frontalis and E. mocsaryi shared the same food source in the flowers of B. excelsa due to differences in their time of visits and non-aggressive way of interacting with the opponent. This result has important implications for pollinating the Brazil nut, and a possible management of X. frontalis and E. mocsaryi, since these two were the most abundant pollinators in the studied locality.

Learning of courtship components in Drosophila mercatorum (Paterson & Wheller) (Diptera, Drosophilidae)

In Drosophila, courtship is an elaborate sequence of behavioural patterns that enables the flies to identify conspecific mates from those of closely related species. This is important because drosophilids usually gather in feeding sites, where males of various species court females vigorously. We investigated the effects of previous experience on D. mercatorum courtship, by testing if virgin males learn to improve their courtship by observing other flies (social learning), or by adjusting their pre-existent behaviour based on previous experiences (facilitation). Behaviours recorded in a controlled environment were courtship latency, courtship (orientation, tapping and wing vibration), mating and other behaviours not related to sexual activities. This study demonstrated that males of D. mercatorum were capable of improving their mating ability based on prior experiences, but they had no social learning on the development of courtship.

Effect of angiotensin-(1-7) on reperfusion arrhythmias in isolated rat hearts

There is increasing evidence that angiotensin-(1-7) (Ang-(1-7)) is an endogenous biologically active component of the renin-angiotensin system (RAS). In the present study, we investigated the effects of Ang-(1-7) on reperfusion arrhythmias in isolated rat hearts. Isolated rat hearts were perfused with two different media, i.e., Krebs-Ringer (2.52 mM CaCl2) and low-Ca2+ Krebs-Ringer (1.12 mM CaCl2). In hearts perfused with Krebs-Ringer, Ang-(1-7) produced a concentration-dependent (27-210 nM) reduction in coronary flow (25% reduction at highest concentration), while only slight and variable changes in contraction force and heart rate were observed. Under the same conditions, angiotensin II (Ang II; 27 and 70 nM) produced a significant reduction in coronary flow (39% and 48%, respectively) associated with a significant increase in force. A decrease in heart rate was also observed. In low-Ca2+ Krebs-Ringer solution, perfusion with Ang-(1-7) or Ang II at 27 nM concentration produced similar changes in coronary flow, contraction force and heart rate. In isolated hearts perfused with normal Krebs-Ringer, Ang-(1-7) produced a significant enhancement of reperfusion arrhythmias revealed by an increase in the incidence and duration of ventricular tachycardia and ventricular fibrillation (more than 30-min duration). The facilitation of reperfusion arrhythmias by Ang-(1-7) was associated with an increase in the magnitude of the decreased force usually observed during the post-ischemic period. The effects of Ang-(1-7) were abolished in isolated rat hearts perfused with low-Ca2+ Krebs-Ringer. The effect of Ang II (27 nM) was similar but less pronounced than that of Ang-(1-7) at the same concentration. These results indicate that the heart is a site of action for Ang-(1-7) and suggest that this heptapeptide may be involved in the mediation of the cardiac effects of the RAS

Agents that affect cAMP levels or protein kinase A activity modulate memory consolidation when injected into rat hippocampus but not amygdala

Male Wistar rats were trained in one-trial step-down inhibitory avoidance using a 0.4-mA footshock. At various times after training (0, 1.5, 3, 6 and 9 h for the animals implanted into the CA1 region of the hippocampus; 0 and 3 h for those implanted into the amygdala), these animals received microinfusions of SKF38393 (7.5 µg/side), SCH23390 (0.5 µg/side), norepinephrine (0.3 µg/side), timolol (0.3 µg/side), 8-OH-DPAT (2.5 µg/side), NAN-190 (2.5 µg/side), forskolin (0.5 µg/side), KT5720 (0.5 µg/side) or 8-Br-cAMP (1.25 µg/side). Rats were tested for retention 24 h after training. When given into the hippocampus 0 h post-training, norepinephrine enhanced memory whereas KT5720 was amnestic. When given 1.5 h after training, all treatments were ineffective. When given 3 or 6 h post-training, 8-Br-cAMP, forskolin, SKF38393, norepinephrine and NAN-190 caused memory facilitation, while KT5720, SCH23390, timolol and 8-OH-DPAT caused retrograde amnesia. Again, at 9 h after training, all treatments were ineffective. When given into the amygdala, norepinephrine caused retrograde facilitation at 0 h after training. The other drugs infused into the amygdala did not cause any significant effect. These data suggest that in the hippocampus, but not in the amygdala, a cAMP/protein kinase A pathway is involved in memory consolidation at 3 and 6 h after training, which is regulated by D1, ß, and 5HT1A receptors. This correlates with data on increased post-training cAMP levels and a dual peak of protein kinase A activity and CREB-P levels (at 0 and 3-6 h) in rat hippocampus after training in this task. These results suggest that the hippocampus, but not the amygdala, is involved in long-term storage of step-down inhibitory avoidance in the rat.

Effects of L-arginine on the diaphragm muscle twitches elicited at different frequencies of nerve stimulation

In rats, the nitric oxide (NO)-synthase pathway is present in skeletal muscle, vascular smooth muscle, and motor nerve terminals. Effects of NO were previously studied in rat neuromuscular preparations receiving low (0.2 Hz) or high (200 Hz) frequencies of stimulation. The latter frequency has always induced tetanic fade. However, in these previous studies we did not determine whether NO facilitates or impairs the neuromuscular transmission in preparations indirectly stimulated at frequencies which facilitate neuromuscular transmission. Thus, the present study was carried out to examine the effects of NO in rat neuromuscular preparations indirectly stimulated at 5 and 50 Hz. The amplitude of muscular contraction observed at the end (B) of a 10-s stimulation was taken as the ratio (R) of that obtained at the start (A) (R = B/A). S-nitroso-N-acetylpenicillamine (200 µM), superoxide dismutase (78 U/ml) and L-arginine (4.7 mM), but not D-arginine (4.7-9.4 mM), produced an increase in R (facilitation of neurotransmission) at 5 Hz. However, reduction in the R value (fade of transmission) was observed at 50 Hz. N G-nitro-L-arginine (8.0 mM) antagonized both the facilitatory and inhibitory effects of L-arginine (4.7 mM). The results suggest that NO may modulate the release of acetylcholine by motor nerve terminals.

The modulation of simple reaction time by the spatial probability of a visual stimulus

Simple reaction time (SRT) in response to visual stimuli can be influenced by many stimulus features. The speed and accuracy with which observers respond to a visual stimulus may be improved by prior knowledge about the stimulus location, which can be obtained by manipulating the spatial probability of the stimulus. However, when higher spatial probability is achieved by holding constant the stimulus location throughout successive trials, the resulting improvement in performance can also be due to local sensory facilitation caused by the recurrent spatial location of a visual target (position priming). The main objective of the present investigation was to quantitatively evaluate the modulation of SRT by the spatial probability structure of a visual stimulus. In two experiments the volunteers had to respond as quickly as possible to the visual target presented on a computer screen by pressing an optic key with the index finger of the dominant hand. Experiment 1 (N = 14) investigated how SRT changed as a function of both the different levels of spatial probability and the subject's explicit knowledge about the precise probability structure of visual stimulation. We found a gradual decrease in SRT with increasing spatial probability of a visual target regardless of the observer's previous knowledge concerning the spatial probability of the stimulus. Error rates, below 2%, were independent of the spatial probability structure of the visual stimulus, suggesting the absence of a speed-accuracy trade-off. Experiment 2 (N = 12) examined whether changes in SRT in response to a spatially recurrent visual target might be accounted for simply by sensory and temporally local facilitation. The findings indicated that the decrease in SRT brought about by a spatially recurrent target was associated with its spatial predictability, and could not be accounted for solely in terms of sensory priming.

Inhibition of return, gap effect and saccadic reaction time to a visual target

Simple manual reaction time (MRT) to a visual target (S2) is shortened when a non-informative cue (S1) is flashed at the S2 location shortly before the onset of S2 (early facilitation). Afterwards, MRT to S2 appearing at the S1 location is lengthened (inhibition of return - IOR). Similar results have been obtained for saccadic reaction time (SRT). Moreover, when there is a temporal gap between offset of the fixation point (FP) and onset of a target (gap paradigm), SRT is shorter than SRT in an overlap paradigm (FP remains on). In the present study, we determined SRT to S2 (10º) after presenting S1 at the same eccentricity (10º) or at a parafoveal position (2º) in the same or in the opposite hemifield. In addition, we employed both gap and overlap paradigms. Twelve subjects were asked not to respond to S1 (2º or 10º) to the right or to the left of FP, but to respond by making a saccadic movement in response to S2. We obtained the following results: 1) a 40-ms gap effect, 2) an interaction between gap effect and IOR, 3) a 39-ms delay (IOR) when S2 appeared at the cued (S1) position, and 4) a smaller (17 ms) but significant inhibition when S1 occurred at 2º in the ipsilateral hemifield. Thus, a parafoveal (2º) S1 elicits an inhibition of SRT towards ipsilateral peripheral targets. Since an inhibition of the ipsilateral hemifield by a 1º eccentric cue has been reported to occur when manual responses are employed, we suggest that the postulated functional link between covert and overt orienting of attention is also valid for parafoveal cues.

Differentiation of autonomic reflex control begins with cellular mechanisms at the first synapse within the nucleus tractus solitarius

Visceral afferents send information via cranial nerves to the nucleus tractus solitarius (NTS). The NTS is the initial step of information processing that culminates in homeostatic reflex responses. Recent evidence suggests that strong afferent synaptic responses in the NTS are most often modulated by depression and this forms a basic principle of central integration of these autonomic pathways. The visceral afferent synapse is uncommonly powerful at the NTS with large unitary response amplitudes and depression rather than facilitation at moderate to high frequencies of activation. Substantial signal depression occurs through multiple mechanisms at this very first brainstem synapse onto second order NTS neurons. This review highlights new approaches to the study of these basic processes featuring patch clamp recordings in NTS brain slices and optical techniques with fluorescent tracers. The vanilloid receptor agonist, capsaicin, distinguishes two classes of second order neurons (capsaicin sensitive or capsaicin resistant) that appear to reflect unmyelinated and myelinated afferent pathways. The differences in cellular properties of these two classes of NTS neurons indicate clear functional differentiation at both the pre- and postsynaptic portions of these first synapses. By virtue of their position at the earliest stage of these pathways, such mechanistic differences probably impart important differentiation in the performance over the entire reflex pathways.

Recombinant viruses as vaccines against viral diseases

Vaccine approaches to infectious diseases are widely applied and appreciated. Amongst them, vectors based on recombinant viruses have shown great promise and play an important role in the development of new vaccines. Many viruses have been investigated for their ability to express proteins from foreign pathogens and induce specific immunological responses against these antigens in vivo. Generally, gene-based vaccines can stimulate potent humoral and cellular immune responses and viral vectors might be an effective strategy for both the delivery of antigen-encoding genes and the facilitation and enhancement of antigen presentation. In order to be utilized as a vaccine carrier, the ideal viral vector should be safe and enable efficient presentation of required pathogen-specific antigens to the immune system. It should also exhibit low intrinsic immunogenicity to allow for its re-administration in order to boost relevant specific immune responses. Furthermore, the vector system must meet criteria that enable its production on a large-scale basis. Several viral vaccine vectors have thus emerged to date, all of them having relative advantages and limits depending on the proposed application, and thus far none of them have proven to be ideal vaccine carriers. In this review we describe the potential, as well as some of the foreseeable obstacles associated with viral vaccine vectors and their use in preventive medicine.

Control of attention by a peripheral visual cue depends on whether the target is difficult to discriminate

The influence of a peripheral cue represented by a gray ring on responsivity to a subsequent target varies. When a vertical line inside a ring was a go target and a white small ring inside a ring was a no-go target, reaction time was shorter at the same location relative to a different location. However, no reaction time difference between the two locations occurred when a white cross inside the ring, instead of the white vertical line inside the ring, was the go target. We investigated whether this last finding was due to a forward masking influence of the cue, a requirement of low attention for the discrimination or a lack of attention mobilization by the cue. In Experiment 1, the intensity of the cue was reduced in an attempt to reduce forward masking. In Experiment 2, the vertical line and the cross were presented in the same block of trials so as to be dealt with a common attentional strategy. In Experiments 3 and 4, the no-go target was a 45º rotated cross inside a ring to increase the difficulty of the discrimination. No evidence was obtained that the cross was forward masked by the cue nor that it demanded less attention to be discriminated from the small ring. There was a facilitation of responsivity by the cue when the small ring was replaced by the rotated cross. The results suggest that when the discrimination to be performed is too easy the cue does not mobilize attention.

5-HT1A autoreceptor modulation of locomotor activity induced by nitric oxide in the rat dorsal raphe nucleus

The dorsal raphe nucleus (DRN) is the origin of ascending serotonergic projections and is considered to be an important component of the brain circuit that mediates anxiety- and depression-related behaviors. A large fraction of DRN serotonin-positive neurons contain nitric oxide (NO). Disruption of NO-mediated neurotransmission in the DRN by NO synthase inhibitors produces anxiolytic- and antidepressant-like effects in rats and also induces nonspecific interference with locomotor activity. We investigated the involvement of the 5-HT1A autoreceptor in the locomotor effects induced by NO in the DRN of male Wistar rats (280-310 g, N = 9-10 per group). The NO donor 3-morpholinosylnomine hydrochloride (SIN-1, 150, and 300 nmol) and the NO scavenger S-3-carboxy-4-hydroxyphenylglycine (carboxy-PTIO, 0.1-3.0 nmol) were injected into the DRN of rats immediately before they were exposed to the open field for 10 min. To evaluate the involvement of the 5-HT1A receptor and the N-methyl-D-aspartate (NMDA) glutamate receptor in the locomotor effects of NO, animals were pretreated with the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 8 nmol), the 5-HT1A receptor antagonist N-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-2-pyridinyl-cyclohexanecarboxamide maleate (WAY-100635, 0.37 nmol), and the NMDA receptor antagonist DL-2-amino-7-phosphonoheptanoic acid (AP7, 1 nmol), followed by microinjection of SIN-1 into the DRN. SIN-1 increased the distance traveled (mean ± SEM) in the open-field test (4431 ± 306.1 cm; F7,63 = 2.44, P = 0.028) and this effect was blocked by previous 8-OH-DPAT (2885 ± 490.4 cm) or AP7 (3335 ± 283.5 cm) administration (P < 0.05, Duncan test). These results indicate that 5-HT1A receptor activation and/or facilitation of glutamate neurotransmission can modulate the locomotor effects induced by NO in the DRN.

Dorsal periaqueductal gray stimulation facilitates anxiety-, but not panic-related, defensive responses in rats tested in the elevated T-maze

The escape response to electrical or chemical stimulation of the dorsal periaqueductal gray matter (DPAG) has been associated with panic attacks. In order to explore the validity of the DPAG stimulation model for the study of panic disorder, we determined if the aversive consequences of the electrical or chemical stimulation of this midbrain area can be detected subsequently in the elevated T-maze. This animal model, derived from the elevated plus-maze, permits the measurement in the same rat of a generalized anxiety- and a panic-related defensive response, i.e., inhibitory avoidance and escape, respectively. Facilitation of inhibitory avoidance, suggesting an anxiogenic effect, was detected in male Wistar rats (200-220 g) tested in the elevated T-maze 30 min after DPAG electrical stimulation (current generated by a sine-wave stimulator, frequency at 60 Hz) or after local microinjection of the GABA A receptor antagonist bicuculline (5 pmol). Previous electrical (5, 15, 30 min, or 24 h before testing) or chemical stimulation of this midbrain area did not affect escape performance in the elevated T-maze or locomotion in an open-field. No change in the two behavioral tasks measured by the elevated T-maze was observed after repetitive (3 trials) electrical stimulation of the DPAG. The results indicate that activation of the DPAG caused a short-lived, but selective, increase in defensive behaviors associated with generalized anxiety.