Fisiologia

The effects of either chronic or acute estrogenic treatment on the "in vitro" vasomotor responses to phenylephrine (1 Oe9-10.' M) and to carbachol ( 1 OS"'-10.' M) of aortic rings excised from ovariectomized rats were analyzed Chronic estrogenic treatment consisted in a single subcutaneous dose of 1 umol estradiol 17-stearate. Effects of acute estrogenic treatment were evaluated by recording the responses of aortic rings excised from untreated ovariectomized rats both before and after the addition of 17l3estradiol to the superfUsing solutions. In order to identify the endothelium-dependent responses each experiment was performed simultaneously on pairs of rings from the same aorta, one with and the other without functional endothelium. The contractile responses to phenylephrine of endothelium-intact vessels were attenuated by chronic estrogenic treatment; this attenuation was mrther increased by preincubation of the vessels with indomethacin and was reverted by No-nitro-L-arginine methyl ester. Either chronic or acute estrogenic treatment enhanced the carbachol-induced endothelium dependent relaxation of phenylephrine-precontracted rings. The results may be explained by assuming that estrogens increase the basal release of both nitric oxide and a cyclooxygenase-dependent vasoconstricting prostanoid as well as the receptor-mediated release of nitric oxide from the endothelium of the rat aorta.

The effects of either chronic or acute estrogenic treatment on the "in vitro" vasomotor responses to phenylephrine (10(-9)-10(-5) M) and to carbachol (10(-9)-10(-5) M) of aortic rings excised from ovariectomized rats were analyzed. Chronic estrogenic treatment consisted in a single subcutaneous dose of 1 mumol estradiol 17-stearate. Effects of acute estrogenic treatment were evaluated by recording the responses of aortic rings excised from untreated ovariectomized rats both before and after the addition of 17 beta-estradiol to the superfusing solutions. In order to identify the endothelium-dependent responses each experiment was performed simultaneously on pairs of rings from the same aorta, one with and the other without functional endothelium. The contractile responses to phenylephrine of endothelium-intact vessels were attenuated by chronic estrogenic treatment; this attenuation was further increased by preincubation of the vessels with indomethacin and was reverted by ...

Acetaldehyde, the most toxic metabolite of ethanol, has been implicated in many toxic effects of ethanol. In the present study, we used rats to investigate the possible changes on the sleep-wake cycle and brain regional concentrations of noradrenaline and serotonin after intraperitoneal administration of several doses of acetaldehyde. Results showed that acetaldehyde significantly decreases the time spent in rapid eye movements sleep and wakefulness and increases the time spent in slow-wave sleep. The neurochemical analysis showed that acetaldehyde significantly increases the 5-hydroxyindolacetic acid content and 5-hydroxyindolacetic acid/serotonin ratio at the bulb and pons. These results suggest that acetaldehyde modifies the metabolism of serotonin which has been implicated in the onset and sustaining of the sleep episodes occurring along the sleep-wake cycle.

Acetaldehyde, the most toxic metabolite of ethanol, has been implicated in many toxic effects of ethanol. In the present study, we used rats to investigate the possible changes on the sleep-wake cycle and brain regional concentrations of noradrenaline and serotonin after intraperitoneal administration of several doses of acetaldehyde. Results showed that acetaldehyde significantly decreases the time spent in rapid eye movements sleep and wakefulness and increases the time spent in slow-wave sleep. The neurochemical analysis showed that acetaldehyde significantly increases the 5-hydroxyindolacetic acid content and 5-hydroxyindolacetic acid/serotonin ratio at the bulb and pons. These results suggest that acetaldehyde modifies the metabolism of serotonin which has been implicated in the onset and sustaining of the sleep episodes occurring along the sleep-wake cycle.

Ozone (O 3) is a component of photochemical smog, which is a major air pollutant and demonstrates properties that are harmful to health because of the toxic properties that are inherent to its powerful oxidizing capabilities. Environmental O 3 exposure is associated with many symptoms related to respiratory disorders, which include loss of lung function, exacerbation of asthma, airway damage, and lung inflammation. The effects of O 3 are not restricted to the respiratory system or function-adverse effects within the central nervous system (CNS) such as decreased cognitive response, decrease in motor activity, headaches, disturbances in the sleepwake cycle, neuronal dysfunctions, cell degeneration, and neurochemical alterations have also been described; furthermore, it has also been proposed that O 3 could have epigenetic effects. O 3 exposure induces the reactive chemical species in the lungs, but the short half-life of these chemical species has led some authors to attribute the injurious mechanisms observed within the lungs to inflammatory processes. However, the damage to the CNS induced by O 3 exposure is not well understood. In this review, the basic mechanisms of inflammation and activation of the immune system by O 3 exposure are described and the potential mechanisms of damage, which include neuroinflammation and oxidative stress, and the signs and symptoms of disturbances within the CNS caused by environmental O 3 exposure are discussed.

In the last 10-15 years, major advances in the percutaneous treatment of atrial septal defects with the use of several occluding devices has occurred with progressive improvement in the results 1-14. Because this approach currently provides excellent occlusive results with minimum morbidity and mortality in short and medium follow-up with obvious advantages regarding the surgical approach 8-17 , it is considered the method of choice for the treatment of selected patients in several medical centers around the world. However, some devices have not been widely accepted by interventionists because they possess characteristics far from those considered ideal 1-7. The most commonly used, including in our group, are the Amplatzer Septal Occluder (AGA Medical Corporation, Golden Valley, MN) 10-16 the CardioSEAL septal occluder and the STARFlex (Nitinol Medical Technologies, Boston, MA) 8,9. Recently, a new device, the Helex septal occluder (W.L. Gore and Associates, Flagstaff, AZ) was introduced for clinical use after encouraging results from experimental studies 18. We report herein the initial experience at 2 Brazilian centers with the new Helex device. Methods The Helex septal occluder is composed of a single flexible nitinol wire frame tridimensionally helically shaped, with a 0.012-inch diameter, covered with a thin polytetrafluoroethylene membrane (PTFE better known as Gore-Tex) (fig.1). For implantation, the frame is sealed in a central mandrel and pulled inside a delivery catheter (9F) (fig 1). As the device is extruded from the catheter, it assumes a helicoidal configuration (therefore the name Helex). It is composed of 2 flexible disks with round borders that are positioned through the hole within the septum. The Helex septal occluder is available on the market in 5 diameters, 15 to 35mm, in 5mm increments. Three small metal loops also called "eyelets" are found in the center of the disks, one more distal (outside the disk on the left side), one between the 2 disks, and another proximal, (outside the disk on the right side). Within the proximal waist is a retrieval cord made of polytetrafluoroethylene 18,19. Objective-To evaluate the initial clinical experience with the Helex septal occluder for percutaneous closure of atrial septal defects. Methods-Ten patients underwent the procedure, 7 patients with ostium secundum atrial septal defects (ASD) with hemodynamic repercussions and 3 patients with pervious foramen ovale (PFO) and a history of stroke. Mean age was 33.8 years and mean weight was 55.4 kg. Mean diameter by transesophageal echocardiography and mean stretched ASD diameter were 11.33 ± 3.3mm, and 15.2 ± 3.8mm, respectively. The Qp/Qs ratio was 1.9 ± 0.3 in patients with ASD. Results-Eleven occluders were placed because a patient with 2 holes needed 2 devices. It was necessary to retrieve and replace 4 devices in 3 patients. We observed immediate residual shunt (< 2mm) in 4 patients with ASD, and in those with patent foramen ovale total occlusion of the defect occurred. No complications were noted, and all patients were discharged on the following day. After 1 month, 2 patients with ASD experienced trivial residual shunts (1mm). In 1 patient, we observed mild prolapse in the proximal disk in the right atrium, without consequences. Conclusion-The Helex septal occluder was safe and effective for occluding small to moderate atrial septal defects. Because the implantation technique is demanding, it requires specific training of the operator. Even so, small technical failures may occur in the beginning of the learning curve, but they do not involve patient safety.

Patients with medically intractable epilepsy are candidates for surgical treatment. The main goals of treatment consist in the ablation of epileptogenic areas, surgical sectioning of the corpus callosum in order to avoid interhemispheric transmission of epileptic electrical activity and stimulation of brain areas capable of inducing inhibition of epileptic activity. Another alternative is the injury of structures such as the dentate nucleus of the cerebellum, which has shown beneficial effects in patients. However, most of these surgical treatments involve healthy brain areas and implicate excessive costs. In this review we discuss previous works that describe surgical techniques and their main post-surgical complications.

Acetaldehyde, the most toxic metabolite of ethanol, has been implicated in many toxic effects of ethanol. In the present study, we used rats to investigate the possible changes on the sleep-wake cycle and brain regional concentrations of noradrenaline and serotonin after intraperitoneal administration of several doses of acetaldehyde. Results showed that acetaldehyde significantly decreases the time spent in rapid eye movements sleep and wakefulness and increases the time spent in slow-wave sleep. The neurochemical analysis showed that acetaldehyde significantly increases the 5-hydroxyindolacetic acid content and 5-hydroxyindolacetic acid/serotonin ratio at the bulb and pons. These results suggest that acetaldehyde modifies the metabolism of serotonin which has been implicated in the onset and sustaining of the sleep episodes occurring along the sleep-wake cycle.

Lesions of the cerebellar dentate nucleus (DN) reduce the after-discharge duration induced by repetitive kindling stimulation and decrease seizures to a lower rank according to Racine's scale. The DN sends cholinergic and glutamatergic fibers to the red nucleus (RN), which is composed of glutamatergic and GABAergic cells. To test the participation of these neurotransmitters in seizures, we compared the levels of glutamate and gamma-aminobutyric acid (GABA) at the RN in a control condition, a kindled stage, and a kindled stage followed by DN lesions. We found that the kindled stage was associated with significant reductions in glutamate and GABA in the RN and that the lesions of the DN in kindled rats reversed the severity of seizures and restored the GABA levels. GAD 65 , a GABA-synthesizing enzyme, was increased in kindled rats and decreased after DN lesions. GAD 65 commonly appears localized at nerve terminals and synapses, and it is only activated when GABA neurotransmission occurs. Thus, it is possible that the increased expression of GAD 65 found in kindled rats could be due to an exacerbated demand for GABA due to kindled seizures. It is known that GABA maintains the inhibitory tone that counterbalances neuronal excitation. The decreased expression of GAD 65 found after the DN lesions indicated that the GABA-synthesizing enzyme was no longer required once it eliminated the excitatory glutamate input to the RN. We thus conclude that DN lesions and their consequent biochemical changes are capable of decreasing the generalized seizures induced by kindling stimulation. V

Neuronal activity in the central nervous system undergoes a variety of electrophysiological changes along the sleep-wake cycle. These changes are modulated by a complex interaction between different neurochemical systems located throughout the brain. Within brainstem and hypothalamus there are a number of neuronal populations that promote wakefulness through the action of different neurotransmitters like noradrenaline, serotonin, histamine and orexin. These systems act together in the generation and maintenance of wakefulness, however although each one contributes in a unique way no neurotransmitter seems to be absolutely necessary because wakefulness is not completely inhibited in the absence of any of them. On the other hand, neurons located in the hypothalamus and brainstem are involved in initiating and maintaining sleep. These neurons contain neurotransmitters such as acetylcholine and GABA and have projections to nuclei involved in wakefulness regulation. Recently, models have...

Cerebellar manipulations have been used successfully in some intractable epileptic patients, however, their intrinsic mechanisms are not fully understood. To further clarify the cerebellar participation in epilepsy, we stimulated 10 rats with 100 Hz, 20 AA at the superior cerebellar peduncle (SCP) during amygdaloid kindling. Results were compared to 10 rats with an electrode placed at the SCP without stimulation and 10 rats without electrodes at the SCP used as control. We found that SCP stimulation increased the theta and alpha rhythms at the contralateral motor cortex. Such a stimulation produced hypertonicity of the forelimbs and tremor of the head. In this condition, we found that each of the behavioral stages during amygdaloid kindling in the SCP stimulated rats was reached earlier, while the amygdaloid electrographic afterdischarges (ADs) were longer during the first and shorter in the final trials as compared to controls. Moreover, amygdaloid ADs recorded exclusively during the behavioral stage-5 were significantly shorter than those recorded in the control conditions. We suggest that SCP stimulation could change the customary electrographic and convulsive expression of amygdala kindling in such a manner as to initially facilitate the limbic seizures and impede the secondary generalized seizures.

Gap junctional communication is mainly mediated by connexin36 and connexin43 in neurons and astrocytes, respectively. It has been suggested that connexin36 allows electrical coupling between neurons whereas connexin43 participates in several process including release of ATP. It was recently reported that blockage of gap junctional communication mediated by connexin36 can disrupt the sleep architecture of the rat. However, there is no experimental approach about effects of sleep deprivation on connexins expression. Therefore, we examined in adult male Wistar rats whether protein levels of connexin36 and connexin43 change in pons, hypothalamus, and frontal cortex after 24 h of total sleep deprivation and 4 h of sleep recovery. Western blot revealed that total sleep deprivation significantly decreases the levels of connexin36 in the hypothalamus and this decrease maintains after sleep recovery. Meanwhile, connexin43 is not altered by total sleep deprivation but interestingly the sleep recovery period induces an increase of this connexin. These results suggest that electrical coupling between hypothalamic neurons could be altered by sleep deprivation and that sleep recovery drives changes in connexin43 expression probably as a mechanism related to ATP release and energy regulation during sleep. NeuroReport

Air pollution is fully acknowledged to represent a major public health issue. Toxic environmental substances, such as ozone, interfere with prenatal development. Animals exposed to ozone (O 3) in utero develop biochemical and morphological alterations. This gas has been proven to decrease cognitive capacity in different species. In the present study, we assessed the possible alterations in memory and spatial learning in the offspring of female rats who were exposed to 1.0 ppm of O 3 embryonic development. Two instruments were used to evaluate possible alterations: the T-maze and a Skinner box. MAPK, ERK, pERK , and NR2B proteins, which are widely regarded as responsible for the learning process in the hippocampus and cortex, were also assessed by immunohistochemistry. We found that male rats exposed to O 3 in utero displayed a significant delay to reach the correct response using the spatial learning test as compared to the control group. The female rats exposed to O 3 showed a significant delay to reach the correct response as compared to the female control group in the Skinner box. We also found that while the male rats showed decrease in significant differences in the expression of NR2B, ERK and increase in MAPK. Females only showed increase in MAPK, pERK and decrease in ERK, when compared to their respective control group. It is possible that the deficits are associated to hormonal expression, inflammation and oxidative stress alterations. In summary, these results suggest that exposure to O 3 can interfere with prenatal development, resulting in learning and memory deficiencies in rats.