Control of the rat angiotensin I converting enzyme gene by CRE-like sequences

We characterized the role of potential cAMP-responsive elements (CRE) in basal and in induced angiotensin converting enzyme (ACE) gene promoter activity in order to shed light on the regulation of somatic ACE expression. We identified stimulators and repressors of basal expression between 122 and 288 bp and between 415 and 1303 bp upstream from the transcription start site, respectively, using a rabbit endothelial cell (REC) line. These regions also contained elements associated with the response to 8BrcAMP. When screening for CRE motifs we found pCRE, a proximal sequence between 209 and 222 bp. dCRE, a distal tandem of two CRE-like sequences conserved between rats, mice and humans, was detected between 834 and 846 bp. Gel retardation analysis of nuclear extracts of REC indicated that pCRE and dCRE bind to the same protein complexes as bound by a canonical CRE. Mutation of pCRE and dCRE in REC established the former as a positive element and the latter as a negative element. In 293 cells, a renal cell line, pCRE and dCRE are negative regulators. Co-transfection of ATF-2 or ATF-2 plus c-Jun repressed ACE promoter activity, suggesting that the ACE gene is controlled by cellular stress. Although mapping of cAMP responsiveness was consistent with roles for pCRE and dCRE, mutation analysis indicated that they were not required for cAMP responsiveness. We conclude that the basal activity of the somatic ACE promoter is controlled by proximal and distal CREs that can act as enhancers or repressors depending on the cell context.

Effects of age and physical activity on the autonomic control of heart rate in healthy men

The effects of the aging process and an active life-style on the autonomic control of heart rate (HR) were investigated in nine young sedentary (YS, 23 ± 2.4 years), 16 young active (YA, 22 ± 2.1 years), 8 older sedentary (OS, 63 ± 2.4 years) and 8 older active (OA, 61 ± 1.1 years) healthy men. Electrocardiogram was continuously recorded for 15 min at rest and for 4 min in the deep breathing test, with a breath rate of 5 to 6 cycles/min in the supine position. Resting HR and RR intervals were analyzed by time (RMSSD index) and frequency domain methods. The power spectral components are reported in normalized units (nu) at low (LF) and high (HF) frequency, and as the LF/HF ratio. The deep breathing test was analyzed by the respiratory sinus arrhythmia indices: expiration/inspiration ratio (E/I) and inspiration-expiration difference (deltaIE). The active groups had lower HR and higher RMSSD index than the sedentary groups (life-style condition: sedentary vs active, P < 0.05). The older groups showed lower HFnu, higher LFnu and higher LF/HF ratio than the young groups (aging effect: young vs older, P < 0.05). The OS group had a lower E/I ratio (1.16) and deltaIE (9.7 bpm) than the other groups studied (YS: 1.38, 22.4 bpm; YA: 1.40, 21.3 bpm; OA: 1.38, 18.5 bpm). The interaction between aging and life-style effects had a P < 0.05. These results suggest that aging reduces HR variability. However, regular physical activity positively affects vagal activity on the heart and consequently attenuates the effects of aging in the autonomic control of HR.

Control of Robot by Means of Human Thought

Brain computer interface (BCI) is a kind of human machine interface, which provides a new interaction method between human and computer or other equipment. The most significant characteristic of BCI system is that its control input is brain electrical activities acquired from the brain instead of traditional input such as hands or eyes. BCI technique has rapidly developed during last two decades and it has mainly worked as an auxiliary technique to help the disable people improve their life qualities. With the appearance of low cost novel electrical devices such as EMOTIV, BCI technique has been applied to the general public through many useful applications including video gaming, virtual reality and virtual keyboard. The purpose of this research is to be familiar with EMOTIV EPOC system and make use of it to build an EEG based BCI system for controlling an industrial manipulator by means of human thought. To build a BCI system, an acquisition program based on EMOTIV EPOC system is designed and a MFC based dialog that works as an operation panel is presented. Furthermore, the inverse kinematics of RV-3SB industrial robot was solved. In the last part of this research, the designed BCI system with human thought input is examined and the results indicate that the system is running smoothly and displays clearly the motion type and the incremental displacement of the motion.

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.

The selective and non-selective cyclooxygenase inhibitors valdecoxib and piroxicam induce the same postoperative analgesia and control of trismus and swelling after lower third molar removal

We compared the clinical efficacy of orally administered valdecoxib and piroxicam for the prevention of pain, trismus and swelling after removal of horizontally and totally intrabony impacted lower third molars. Twenty-five patients were scheduled to undergo removal of symmetrically positioned lower third molars in two separate appointments. Valdecoxib (40 mg) or piroxicam (20 mg) was administered in a double-blind, randomized and crossed manner for 4 days after the surgical procedures. Objective and subjective parameters were recorded for comparison of postoperative courses. Both agents were effective for postoperative pain relief (N = 19). There was a similar mouth opening at suture removal compared with the preoperative values (86.14 ± 4.36 and 93.12 ± 3.70% of the initial measure for valdecoxib and piroxicam, respectively; ANOVA). There was no significant difference regarding the total amount of rescue medication taken by the patients treated with valdecoxib or piroxicam (173.08 ± 91.21 and 461.54 ± 199.85 mg, respectively; Wilcoxon test). There were no significant differences concerning the swelling observed on the second postoperative day compared to baseline measures (6.15 ± 1.84 and 8.46 ± 2.04 mm for valdecoxib and piroxicam, respectively; ANOVA) or on the seventh postoperative day (1.69 ± 1.61 and 2.23 ± 2.09 mm for valdecoxib and piroxicam, respectively; ANOVA). The cyclooxygenase-2 selective inhibitor valdecoxib is as effective as the non-selective cyclooxygenase inhibitor piroxicam for pain, trismus and swelling control after removal of horizontally and totally intrabony impacted lower third molars.

Central actions of glucocorticoids in the control of body fluid homeostasis: Review

The involvement of the hypothalamic-pituitary-adrenal axis in the control of body fluid homeostasis has been extensively investigated in the past few years. In the present study, we reviewed the recent results obtained using different approaches to investigate the effects of glucocorticoids on the mechanisms of oxytocin and vasopressin synthesis and secretion in response to acute and chronic plasma volume and osmolality changes. The data presented here suggest that glucocorticoids are not only involved in the mechanisms underlying the fast release but also in the transcriptional events that lead to decreased synthesis and secretion of these neuropeptides, particularly oxytocin, under diverse experimental conditions of altered fluid volume and tonicity. The endocannabinoid system, through its effects on glutamatergic neurotransmission within the hypothalamus and the nuclear factor κB-mediated transcriptional activity, seems to be also involved in the specific mechanisms by which glucocorticoids exert their central effects on neurohypophyseal hormone synthesis and secretion.

Evidence that blood pressure remains under the control of arterial baroreceptors in renal hypertensive rats

The purpose of the present study was to determine the range of the influence of the baroreflex on blood pressure in chronic renal hypertensive rats. Supramaximal electrical stimulation of the aortic depressor nerve and section of the baroreceptor nerves (sinoaortic denervation) were used to obtain a global analysis of the baroreceptor-sympathetic reflex in normotensive control and in chronic (2 months) 1-kidney, 1-clip hypertensive rats. The fall in blood pressure produced by electrical baroreceptor stimulation was greater in renal hypertensive rats than in normotensive controls (right nerve: -47 ± 8 vs -23 ± 4 mmHg; left nerve: -51 ± 7 vs -30 ± 4 mmHg; and both right and left nerves: -50 ± 8 vs -30 ± 4 mmHg; P < 0.05). Furthermore, the increase in blood pressure level produced by baroreceptor denervation in chronic renal hypertensive rats was similar to that observed in control animals 2-5 h (control: 163 ± 5 vs 121 ± 1 mmHg; 1K-1C: 203 ± 7 vs 170 ± 5 mmHg; P < 0.05) and 24 h (control: 149 ± 3 vs 121 ± 1 mmHg; 1K-1C: 198 ± 8 vs 170 ± 5 mmHg; P < 0.05) after sinoaortic denervation. Taken together, these data indicate that the central and peripheral components of the baroreflex are acting efficiently at higher arterial pressure in renal hypertensive rats when the aortic nerve is maximally stimulated or the activity is abolished.

Control of respiration in fish, amphibians and reptiles

Fish and amphibians utilise a suction/force pump to ventilate gills or lungs, with the respiratory muscles innervated by cranial nerves, while reptiles have a thoracic, aspiratory pump innervated by spinal nerves. However, fish can recruit a hypobranchial pump for active jaw occlusion during hypoxia, using feeding muscles innervated by anterior spinal nerves. This same pump is used to ventilate the air-breathing organ in air-breathing fishes. Some reptiles retain a buccal force pump for use during hypoxia or exercise. All vertebrates have respiratory rhythm generators (RRG) located in the brainstem. In cyclostomes and possibly jawed fishes, this may comprise elements of the trigeminal nucleus, though in the latter group RRG neurons have been located in the reticular formation. In air-breathing fishes and amphibians, there may be separate RRG for gill and lung ventilation. There is some evidence for multiple RRG in reptiles. Both amphibians and reptiles show episodic breathing patterns that may be centrally generated, though they do respond to changes in oxygen supply. Fish and larval amphibians have chemoreceptors sensitive to oxygen partial pressure located on the gills. Hypoxia induces increased ventilation and a reflex bradycardia and may trigger aquatic surface respiration or air-breathing, though these latter activities also respond to behavioural cues. Adult amphibians and reptiles have peripheral chemoreceptors located on the carotid arteries and central chemoreceptors sensitive to blood carbon dioxide levels. Lung perfusion may be regulated by cardiac shunting and lung ventilation stimulates lung stretch receptors.

Autonomic control of cardiorespiratory interactions in fish, amphibians and reptiles

Control of the heart rate and cardiorespiratory interactions (CRI) is predominantly parasympathetic in all jawed vertebrates, with the sympathetic nervous system having some influence in tetrapods. Respiratory sinus arrhythmia (RSA) has been described as a solely mammalian phenomenon but respiration-related beat-to-beat control of the heart has been described in fish and reptiles. Though they are both important, the relative roles of feed-forward central control and peripheral reflexes in generating CRI vary between groups of fishes and probably between other vertebrates. CRI may relate to two locations for the vagal preganglionic neurons (VPN) and in particular cardiac VPN in the brainstem. This has been described in representatives from all vertebrate groups, though the proportion in each location is variable. Air-breathing fishes, amphibians and reptiles breathe discontinuously and the onset of a bout of breathing is characteristically accompanied by an immediate increase in heart rate plus, in the latter two groups, a left-right shunting of blood through the pulmonary circuit. Both the increase in heart rate and opening of a sphincter on the pulmonary artery are due to withdrawal of vagal tone. An increase in heart rate following a meal in snakes is related to withdrawal of vagal tone plus a non-adrenergic-non-cholinergic effect that may be due to humoral factors released by the gut. Histamine is one candidate for this role.

Follow-up of patients treated with retinoic acid for the control of radioiodine non-responsive advanced thyroid carcinoma

During thyroid tumor progression, cellular de-differentiation may occur and it is commonly accompanied by metastatic spread and loss of iodine uptake. Retinoic acid (RA) administration might increase iodine uptake in about 40% of patients, suggesting that RA could be a promising therapeutic option for radioiodine non-responsive thyroid carcinoma, although a prospective study with a long-term follow-up has not been reported. This was a clinical prospective study assessing the value of 13-cis-RA in patients with advanced thyroid carcinoma and its impact on major outcomes such as tumor regression and cancer-related death with a long-term follow-up of patients submitted to radioiodine (131I) therapy after RA administration. Sixteen patients with inoperable disease and no significant radioiodine uptake on post-therapy scan were selected. Patients were treated orally with 13-cis-RA at a dose of 1.0 to 1.5 mg·kg-1·day-1 for 5 weeks and then submitted to radioiodine therapy (150 mCi) after thyroxine withdrawal. A whole body scan was obtained 5 to 7 days after the radioactive iodine therapy. RECIST criteria were used to evaluate the response. An objective partial response rate was observed in 18.8%, a stable disease rate in 25% and a progression disease rate in 56.2%. Five patients died (62.5%) in the group classified as progression of disease. Progression-free survival rate (PFS) ranged from 72 to 12 months, with a median PFS of 26.5 months. RA may be an option for advanced de-differentiated thyroid cancer, due to the low rate of side effects.

Involvement of β3-adrenergic receptors in the control of food intake in rats

This study examined the food intake changes evoked by intracerebroventricular (icv) injection of a selective agonist (BRL37344, 2 and 20 nmol) or antagonist (SR59230A, 10 and 50 nmol) of β3-adrenergic receptors in 24-h fasted rats (adult male Wistar rats, 200-350 g, N = 6/treatment). The animals were also pretreated with saline icv (SAL) or SR59230A (50 nmol) followed by BRL37344 (20 nmol) or SAL in order to determine the selectivity of the effects evoked by BRL37344 on food intake or the selectivity of the effects evoked by SR59230A on risk assessment (RA) behavior. The highest dose of BRL37344 (N = 7) decreased food intake 1 h after the treatment (6.4 ± 0.5 g in SAL-treated vs 4.2 ± 0.8 g in drug-treated rats). While both doses of SR59230A failed to affect food intake (5.1 ± 1.1 g for 10 nmol and 6.0 ± 1.8 g for 50 nmol), this treatment reduced the RA frequency (number/30 min) (4 ± 2 for SAL-treated vs 1 ± 1 for 10 nmol and 0.5 ± 1 for 50 nmol SR59230A-treated rats), an ethological parameter related to anxiety. While pretreatment with SR59230A (7.0 ± 0.5 g) abolished the hypophagia induced by BRL37344 (3.6 ± 0.9 g), BRL37344 suppressed the reduction in RA frequency caused by SR59230A. These results show that the hypophagia caused by BRL37344 is selectively mediated by β3-adrenergic receptors within the central nervous system. Moreover, they suggest the involvement of these receptors in the control of anxiety.

Role of α2-adrenoceptors in the lateral parabrachial nucleus in the control of body fluid homeostasis

Central α2-adrenoceptors and the pontine lateral parabrachial nucleus (LPBN) are involved in the control of sodium and water intake. Bilateral injections of moxonidine (α2-adrenergic/imidazoline receptor agonist) or noradrenaline into the LPBN strongly increases 0.3 M NaCl intake induced by a combined treatment of furosemide plus captopril. Injection of moxonidine into the LPBN also increases hypertonic NaCl and water intake and reduces oxytocin secretion, urinary sodium, and water excreted by cell-dehydrated rats, causing a positive sodium and water balance, which suggests that moxonidine injected into the LPBN deactivates mechanisms that restrain body fluid volume expansion. Pretreatment with specific α2-adrenoceptor antagonists injected into the LPBN abolishes the behavioral and renal effects of moxonidine or noradrenaline injected into the same area, suggesting that these effects depend on activation of LPBN α2-adrenoceptors. In fluid-depleted rats, the palatability of sodium is reduced by ingestion of hypertonic NaCl, limiting intake. However, in rats treated with moxonidine injected into the LPBN, the NaCl palatability remains high, even after ingestion of significant amounts of 0.3 M NaCl. The changes in behavioral and renal responses produced by activation of α2-adrenoceptors in the LPBN are probably a consequence of reduction of oxytocin secretion and blockade of inhibitory signals that affect sodium palatability. In this review, a model is proposed to show how activation of α2-adrenoceptors in the LPBN may affect palatability and, consequently, ingestion of sodium as well as renal sodium excretion.

Alternative chromatographic system for the quality control of lipophilic technetium-99m radiopharmaceuticals such as [99mTc(MIBI)6]+

Knowledge of the radiochemical purity of radiopharmaceuticals is mandatory and can be evaluated by several methods and techniques. Planar chromatography is the technique normally employed in nuclear medicine since it is simple, rapid and usually of low cost. There is no standard system for the chromatographic technique, but price, separation efficiency and short time for execution must be considered. We have studied an alternative system using common chromatographic stationary phase and alcohol or alcohol:chloroform mixtures as the mobile phase, using the lipophilic radiopharmaceutical [99mTc(MIBI)6]+ as a model. Whatman 1 modified phase paper and absolute ethanol, Whatman 1 paper and methanol:chloroform (25:75), Whatman 3MM paper and ethanol:chloroform (25:75), and the more expensive ITLC-SG and 1-propanol:chloroform (10:90) were suitable systems for the direct determination of radiochemical purity of [99mTc(MIBI)6]+ since impurities such as99mTc-reduced-hydrolyzed (RH),99mTcO4- and [99mTc(cysteine)2]-complex were completely separated from the radiopharmaceutical, which moved toward the front of chromatographic systems while impurities were retained at the origin. The time required for analysis was 4 to 15 min, which is appropriate for nuclear medicine routines.

Physicochemical analyses indicated to the quality control of royal jelly with honey

Royal jelly (RJ) is used as a revitalizing tonic. In order to avoid rejection to its acid taste, it is added to honey. There are regulations for honey and for royal jelly separately but not for the mixture. The objective of this work is, therefore, to verify if the same methods used for pure honey quality control can be used for honey mixed with royal jelly and also the presence of RJ through 10-HDA determination. The methods used were: moisture, reducing sugars, apparent sucrose, ash, hydroxymethylfurfural, insoluble solids, diastase activity, acidity and 10-HDA. Samples were prepared by adding 0-100% of RJ in honey. The results showed that the ash method was the only suitable one to all the samples. The acidity analysis (direct titration) was suitable to 0-30%RJ samples; the reducing sugar analysis was suitable to 0-20% RJ samples. Concerning moisture analysis the refractometric method is suitable to 0-10% RJ and the Infra Red method is suggested to be used for samples with more than 10% RJ. The methods for diastase activity, HMF, apparent sucrose and insoluble solids were inadequate for all samples with RJ. The presence of RJ in the samples was confirmed by the 10-HDA analyses.

Effect of Leuconostoc mesenteroides 11 bacteriocin in the multiplication control of Listeria monocytogenes 4b

The activity of a crude preparation of bacteriocin produced by the chicken meat isolate Leuconostoc mesenteroides 11, was evaluated at 8ºC and 15ºC against Listeria monocytogenes. The pathogen was inoculated in a crude preparation of the bacteriocin and its population was enumerated after 0.5 and 10 days. The title of the bacteriocin in the preparation was determined immediately before inoculation and after 10 days of incubation at both temperatures. As a negative control, a non-bacteriocin producing strain, Leuconostoc mesenteroides A13, was used. Bacteriocin of L. mesenteroides 11 partially inhibited L. monocytogenes at 8ºC, but at 15ºC it was unable to prevent growth of the pathogen. Our findings suggest that the use of the semi-purified bacteriocin of L. mesenteroides 11 probably will not be suitable as a single hurdle to prevent L. monocytogenes growth in foods.