962 resultados para Repeated Bout Effect


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Abuse of cocaine and androgenic-anabolic steroids has become a serious public health problem. Despite reports of an increase in the incidence of simultaneous illicit use of these substances, potential toxic interactions between cocaine and androgenic-anabolic steroids in the cardiovascular system are unknown. In the present study, we investigated the effect of single or combined administration of testosterone and cocaine for 1 or 10 consecutive days on basal cardiovascular parameters, baroreflex activity, and hemodynamic responses to vasoactive agents in unanesthetized rats. Ten-day combined administration of testosterone and cocaine increased baseline arterial pressure. Changes in arterial pressure were associated with altered baroreflex activity and impairment of both hypotensive response to intravenous sodium nitroprusside and pressor effect of intravenous phenylephrine. Chronic single administration of either testosterone or cocaine did not affect baseline arterial pressure. However, testosterone-treated animals presented rest bradycardia, cardiac hypertrophy, alterations in baroreflex activity, and enhanced response to sodium nitroprusside. Repeated administration of cocaine affected baroreflex activity and impaired vascular responsiveness to both sodium nitroprusside and phenylephrine. One-day single or combined administration of the drugs did not affect any parameter investigated. In conclusion, the present results suggest a potential interaction between toxic effects of cocaine and testosterone on the cardiovascular activity. Changes in baseline arterial pressure after combined administration of these 2 drugs may result from alterations in baroreflex activity and impairment of vascular responsiveness to vasoactive agents.

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Post-exercise hypotension (PEH), the reduction of blood pressure (BP) after a single bout of exercise, is of great clinical relevance. As the magnitude of this phenomenon seems to be dependent on pre-exercise BP values and chronic exercise training in hypertensive individuals leads to BP reduction; PEH could be attenuated in this context. Therefore, the aim of the present study was to investigate whether PEH remains constant after resistance exercise training. Fifteen hypertensive individuals (46 +/- 8 years; 88 +/- 16 kg; 30 +/- 6% body fat; 150 +/- 13/93 +/- 5mm Hg systolic/diastolic BP, SBP/DBP) were withdrawn from medication and performed 12 weeks of moderate-intensity resistance training. Parameters of cardiovascular function were evaluated before and after the training period. Before the training program, hypertensive volunteers showed significant PEH. After an acute moderate-intensity resistance exercise session with three sets of 12 repetitions (60% of one repetition maximum) and a total of seven exercises, BP was reduced post-exercise (45-60 min) by an average of aproximately -22mm Hg for SBP, -8mm Hg for DBP and -13 mm Hg for mean arterial pressure (P<0.05). However, this acute hypotensive effect did not occur after the 12 weeks of training (P>0.05). In conclusion, our data demonstrate that PEH, following an acute exercise session, can indeed be attenuated after 12 weeks of training in hypertensive stage 1 patients not using antihypertensive medication. Journal of Human Hypertension (2012) 26, 533-539; doi:10.1038/jhh.2011.67; published online 7 July 2011

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Study Design. Ex vivo study of the mechanical performance of cylindrical and dual-core pedicle screws after insertion, removal, and reinsertion in the same hole. Objective. To evaluate the effect of repeated use of same screw hole on the insertion torque and the retentive strength of the cylindrical and dual-core screws. Summary of Background Data. Insertion and removal of pedicle screws is sometimes necessary during surgical procedure to assess the integrity of the pilot-hole wall. However, this maneuver may compromise the implant-holding capacity. Methods. Sixty thoracolombar vertebrae (T13-L5), harvested from 10 healthy calves, were used to insert 2 different designs of pedicle screws: cylindrical (5.0-mm outer diameter) and dual-core screws (5.2-mm outer diameter). Three experimental groups were created on the basis of the number of insertions of the screws and 2 subgroups were established according to the core pedicle screw design (dual-core and cylindrical). The insertion torque was measured during initial insertion, second insertion, and third insertion. Pullout screw tests were performed using a universal testing machine to evaluate the pullout strength after initial insertion, second insertion, and third insertion. Results. Significant reductions of 38% in mean insertion torque and 30% in mean pullout strength of dual-core screw were observed between the initial insertion and the third insertion. The cylindrical screw observed significant reductions of 52.5% in mean insertion torque and 42.3% in mean pullout strength between the initial insertion and the third insertion. A reduction of mean insertion torque and pullout strength between the first insertion and the second insertion but without significance was also observed for both types of screws. Conclusion. Insertions and reinsertion of either cylindrical or dual-core pedicle screws have compromised insertion torque and pullout strength of the implants as measured by mechanical tests.

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This study sought to evaluate the efficacy of passive ultrasonic irrigation (PUI) on removing the smear layer and debris from root dentin using scanning electron microscopy (SEM). Twenty-five bovine incisors were manually prepared and divided into three groups according to the final irrigation protocol: EDTA, final irrigation with 12 mL of 17% EDTA for 3 minutes followed by 5 mL of 2.5% NaOCl; EDTA=PUI, final flush with 4 mL of 17% EDTA and PUI for 30 seconds. These procedures were repeated three times to standardize the volume of the irrigant. Control group, after preparation, the specimens were irrigated only with 17 mL of 2.5% NaOCl. The roots were fractured and analyzed using SEM. The intragroup analysis revealed that the EDTA=PUI protocol removed a higher amount of debris at the cervical third (P 5 0.03). The intergroup analysis revealed that EDTA=PUI presented the lowest amount of debris at the cervical third (P 5 0.007). Smear layer scores were higher in the control group compared with the EDTA and EDTA=PUI groups, but only at the cervical third (P 50.02). None of the final irrigant protocols completely removed the smear layer and debris. EDTA=PUI only improved the removal of debris at the cervical third.

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Objectives: Stimulation of salivary flow is considered a preventive strategy for dental erosion. Alternatively, products containing calcium phosphate, such as a complex of casein phosphopeptide–amorphous calcium phosphate (CPP–ACP), have also been tested against dental erosion. Therefore, this in situ study analyzed the effect of chewing gum containing CPP–ACP on the mineral precipitation of initial bovine enamel erosion lesions. Methods: Twelve healthy adult subjects wore palatal appliances with two eroded bovine enamel samples. The erosion lesions were produced by immersion in 0.1% citric acid (pH 2.5) for 7 min. During three experimental crossover in situ phases (1 day each), the subjects chewed a type of gum, 3 times for 30 min, in each phase: with CPP–ACP (trident total), without CPP–ACP (trident), and no chewing gum (control). The Knoop surface microhardness was measured at baseline, after erosion in vitro and the mineral precipitation in situ. The differences in the degree of mineral precipitation were analyzed using repeated measures (RM-) ANOVA and post hoc Tukey’s test ( p < 0.05). Results: Significant differences were found among the remineralizing treatments ( p < 0.0001). Chewing gum (19% of microhardness recovery) improved the mineral precipitation compared to control (10%) and the addition of CPP–ACP into the gum promoted the best mineral precipitation effect (30%). Conclusions: Under this protocol, CPP–ACP chewing gum improved the mineral precipitation of eroded enamel. Clinical significance: Since the prevalence of dental erosion is steadily increasing, CPP–ACP chewing gum might be an important strategy to reduce th eprogression of initial erosion lesions.

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Abstract Background The current treatments for anxiety disorders and depression have multiple adverse effects in addition to a delayed onset of action, which has prompted efforts to find new substances with potential activity in these disorders. Citrus aurantium was chosen based on ethnopharmacological data because traditional medicine refers to the Citrus genus as useful in diminishing the symptoms of anxiety or insomnia, and C. aurantium has more recently been proposed as an adjuvant for antidepressants. In the present work, we investigated the biological activity underlying the anxiolytic and antidepressant effects of C. aurantium essential oil (EO), the putative mechanism of the anxiolytic-like effect, and the neurochemical changes in specific brain structures of mice after acute treatment. We also monitored the mice for possible signs of toxicity after a 14-day treatment. Methods The anxiolytic-like activity of the EO was investigated in a light/dark box, and the antidepressant activity was investigated in a forced swim test. Flumazenil, a competitive antagonist of benzodiazepine binding, and the selective 5-HT1A receptor antagonist WAY100635 were used in the experimental procedures to determine the mechanism of action of the EO. To exclude false positive results due to motor impairment, the mice were submitted to the rotarod test. Results The data suggest that the anxiolytic-like activity observed in the light/dark box procedure after acute (5 mg/kg) or 14-day repeated (1 mg/kg/day) dosing was mediated by the serotonergic system (5-HT1A receptors). Acute treatment with the EO showed no activity in the forced swim test, which is sensitive to antidepressants. A neurochemical evaluation showed no alterations in neurotransmitter levels in the cortex, the striatum, the pons, and the hypothalamus. Furthermore, no locomotor impairment or signs of toxicity or biochemical changes, except a reduction in cholesterol levels, were observed after treatment with the EO. Conclusion This work contributes to a better understanding of the biological activity of C. aurantium EO by characterizing the mechanism of action underlying its anxiolytic-like activity.

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The aims of this study were to test (i) the effect of time of tissue and RNA extracts storage on ice and (ii) the effect of repeated freeze–thaw cycles on RNA integrity and gene expression of bovine reproductive tissues. Fragments of endometrium (ENDO), corpus luteum (CL) and ampulla (AMP) were subdivided and incubated for 0, 1, 3, 6, 12 or 24 h on ice. RNA extracts were incubated on ice for 0, 3, 12 or 24 h, or exposed to 1, 2, 4 or 6 freeze–thaw cycles. RNA integrity number (RIN) was estimated. Expression of progesterone receptor (PGR) and cyclophilin genes from RNA extracts stored on ice for 0 or 24 h, and 1 or 6 freeze–thaw cycles was measured by qPCR. Tissue and RNA extract incubation on ice, and repeated freeze–thaw cycles did not affect RIN values of RNA from ENDO, CL or AMP. Storage on ice or exposure to freeze–thaw cycles did not affect Cq values for PGR or cyclophilin genes. In conclusion, neither generalized RNA degradation nor specific RNA degradation was affected by storage of tissue or RNA extracts on ice for up to 24 h, or by up to 6 freeze–thaw cycles of RNA extracts obtained from bovine ENDO, CL and AMP.

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[EN] The principal aim of this investigation was to determine the influence of blood haemoglobin concentration ([Hb]) on maximal exercise capacity and maximal O(2) consumption (V(O(2),max)) in healthy subjects acclimatised to high altitude. Secondarily, we examined the effects of [Hb] on the regulation of cardiac output (CO), blood pressure and muscular blood flow (LBF) during exercise. Eight Danish lowlanders (three females and five males; 24 +/- 0.6 years, mean +/- S.E.M.) performed submaximal and maximal exercise on a cycle ergometer after 9 weeks at an altitude of 5260 m (Mt Chacaltaya, Bolivia). This was done first with the high [Hb] resulting from acclimatisation and again 2-4 days later, 1 h after isovolaemic haemodilution with Dextran 70 to near sea level [Hb]. After measurements at maximal exercise while breathing air at each [Hb], subjects were switched to hyperoxia (55 % O(2) in N(2)) and the measurements were repeated, increasing the work rate as tolerated. Hyperoxia increased maximal power output and leg V(O(2),max), showing that breathing ambient air at 5260 m, V(O(2),max) is limited by the availability of O(2) rather than by muscular oxidative capacity. Altitude increased [Hb] by 36 % from 136 +/- 5 to 185 +/- 5 g l(-1) (P < 0.001), while haemodilution (replacing 1 l of blood with 1 l of 6 % Dextran) lowered [Hb] by 24 % to 142 +/- 6 g l(-1) (P < 0.001). Haemodilution had no effect on maximal pulmonary or leg V(O(2),max), or power output. Despite higher LBF, leg O(2) delivery was reduced and maximal V(O(2)) was thus maintained by higher O(2) extraction. While CO increased linearly with work rate irrespective of [Hb] or inspired oxygen fraction (F(I,O(2))), both LBF and leg vascular conductance were systematically higher when [Hb] was low. Close and significant relationships were seen between LBF (and CO) and both plasma noradrenaline and K(+) concentrations, independently of [Hb] and F(I,O(2)). In summary, under conditions where O(2) supply limits maximal exercise, the increase in [Hb] with altitude acclimatisation does not improve maximal exercise capacity or V(O(2),max), and does not alter peak CO. However, LBF and vascular conductance are higher at altitude when [Hb] is lowered to sea level values, with both relating closely to catecholamine and potassium concentrations. This suggests that the lack of effect of [Hb] on V(O(2),max) may involve reciprocal changes in LBF via local metabolic control of the muscle vasculature.

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The aim of this study was to determine if extracorporeal shock wave therapy (ESWT) in vivo affects the structural integrity of articular cartilage. A single bout of ESWT (1500 shock waves of 0.5 mJ/mm(2)) was applied to femoral heads of 18 adult Sprague-Dawley rats. Two sham-treated animals served as controls. Cartilage of each femoral head was harvested at 1, 4, or 10 weeks after ESWT (n = 6 per treatment group) and scored on safranin-O-stained sections. Expression of tenascin-C and chitinase 3-like protein 1 (Chi3L1) was analyzed by immunohistochemistry. Quantitative real-time polymerase chain reaction (PCR) was used to examine collagen (II)alpha(1) (COL2A1) expression and chondrocyte morphology was investigated by transmission electron microscopy no changes in Mankin scores were observed after ESWT. Positive immunostaining for tenascin-C and Chi3L1 was found up to 10 weeks after ESWT in experimental but not in control cartilage. COL2A1 mRNA was increased in samples 1 and 4 weeks after ESWT. Alterations found on the ultrastructural level showed expansion of the rough-surfaced endoplasmatic reticulum, detachment of the cell membrane and necrotic chondrocytes. Extracorporeal shock waves caused alterations of hyaline cartilage on a molecular and ultrastructural level that were distinctly different from control. Similar changes were described before in the very early phase of osteoarthritis (OA). High-energy ESWT might therefore cause degenerative changes in hyaline cartilage as they are found in initial OA.

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The purpose of this study was to evaluate the anti-nociceptive activity of ketamine and isoflurane in horses using a limb withdrawal reflex (WR) model. Single and repeated stimulations were applied to the digital nerve of the left forelimb in ponies anaesthetised with isoflurane before, during and after intravenous administration of racemic ketamine. Surface electromyographic activity was recorded from the deltoid muscle. Higher stimulation intensity was required to evoke a reflex during ketamine administration. Furthermore, the amplitudes of response to stimulations were significantly and dose-dependently depressed and a flattening of the stimulus-response curves was observed. The reflex activity recovered partially once the ketamine infusion finished. The results demonstrated that the limb WR can be used to quantify the temporal effect of ketamine on the sensory-motor processing in ponies anaesthetised with isoflurane.

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The activation of 5-hydroxytryptamine-3 (5-HT-3) receptors in spinal cord can enhance intrinsic spinal mechanisms of central hypersensitivity, possibly leading to exaggerated pain responses. Clinical studies suggest that 5-HT-3 receptor antagonists may have an analgesic effect. This randomized, double-blind, placebo-controlled crossover study tested the hypothesis that the 5-HT-3 receptor antagonist tropisetron attenuates pain and central hypersensitivity in patients with chronic low back pain. Thirty patients with chronic low back pain, 15 of whom were women (aged 53 ± 14 years) and 15 men (aged 48 ± 14 years), were studied. A single intravenous injection of 0.9% saline solution, tropisetron 2mg, and tropisetron 5mg was administrated in 3 different sessions, in a double-blind crossover manner. The main outcome was the visual analogue scale (VAS) score of spontaneous low back pain before, and 15, 30, 60, and 90 minutes after drug administration. Secondary outcomes were nociceptive withdrawal reflexes to single and repeated electrical stimulation, area of reflex receptive fields, pressure pain detection and tolerance thresholds, conditioned pain modulation, and area of clinical pain. The data were analyzed by analysis of variance and panel multiple regressions. All 3 treatments reduced VAS scores. However, there was no statistically significant difference between tropisetron and placebo in VAS scores. Compared to placebo, tropisetron produced a statistically significant increase in pain threshold after single electrical stimulation, but no difference in all other secondary outcomes was found. A single-dose intravenous administration of tropisetron in patients with chronic low back pain had no significant specific effect on intensity of pain and most parameters of central hypersensitivity.

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Repetitive proteins (RP) of Trypanosoma cruzi are highly present in the parasite and are strongly recognized by sera from Chagas' disease patients. Flagelar Repetitive Antigen (FRA), which is expressed in all steps of the parasite life cycle, is the RP that displays the greatest number of aminoacids per repeat and has been indicated as one of the most suitable candidate for diagnostic test because of its high performance in immunoassays. Here we analyzed the influence of the number of repeats on the immunogenic and antigenic properties of the antigen. Recombinant proteins containing one, two, and four tandem repeats of FRA (FRA1, FRA2, and FRA4, respectively) were obtained and the immune response induced by an equal amount of repeats was evaluated in a mouse model. The reactivity of specific antibodies present in sera from patients naturally infected with T. cruzi was also assessed against FRA1, FRA2, and FRA4 proteins, and the relative avidity was analyzed. We determined that the number of repeats did not increase the humoral response against the antigen and this result was reproduced when the repeated motifs were alone or fused to a non-repetitive protein. By contrast, the binding affinity of specific human antibodies increases with the number of repeated motifs in FRA antigen. We then concluded that the high ability of FRA to be recognized by specific antibodies from infected individuals is mainly due to a favorable polyvalent interaction between the antigen and the antibodies. In accordance with experimental results, a 3D model was proposed and B epitope in FRA1, FRA2, and FRA4 were predicted.

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INTRODUCTION: The objective was to study the effects of a lung recruitment procedure by stepwise increases of mean airway pressure upon organ blood flow and hemodynamics during high-frequency oscillatory ventilation (HFOV) versus pressure-controlled ventilation (PCV) in experimental lung injury. METHODS: Lung damage was induced by repeated lung lavages in seven anesthetized pigs (23-26 kg). In randomized order, HFOV and PCV were performed with a fixed sequence of mean airway pressure increases (20, 25, and 30 mbar every 30 minutes). The transpulmonary pressure, systemic hemodynamics, intracranial pressure, cerebral perfusion pressure, organ blood flow (fluorescent microspheres), arterial and mixed venous blood gases, and calculated pulmonary shunt were determined at each mean airway pressure setting. RESULTS: The transpulmonary pressure increased during lung recruitment (HFOV, from 15 +/- 3 mbar to 22 +/- 2 mbar, P < 0.05; PCV, from 15 +/- 3 mbar to 23 +/- 2 mbar, P < 0.05), and high airway pressures resulted in elevated left ventricular end-diastolic pressure (HFOV, from 3 +/- 1 mmHg to 6 +/- 3 mmHg, P < 0.05; PCV, from 2 +/- 1 mmHg to 7 +/- 3 mmHg, P < 0.05), pulmonary artery occlusion pressure (HFOV, from 12 +/- 2 mmHg to 16 +/- 2 mmHg, P < 0.05; PCV, from 13 +/- 2 mmHg to 15 +/- 2 mmHg, P < 0.05), and intracranial pressure (HFOV, from 14 +/- 2 mmHg to 16 +/- 2 mmHg, P < 0.05; PCV, from 15 +/- 3 mmHg to 17 +/- 2 mmHg, P < 0.05). Simultaneously, the mean arterial pressure (HFOV, from 89 +/- 7 mmHg to 79 +/- 9 mmHg, P < 0.05; PCV, from 91 +/- 8 mmHg to 81 +/- 8 mmHg, P < 0.05), cardiac output (HFOV, from 3.9 +/- 0.4 l/minute to 3.5 +/- 0.3 l/minute, P < 0.05; PCV, from 3.8 +/- 0.6 l/minute to 3.4 +/- 0.3 l/minute, P < 0.05), and stroke volume (HFOV, from 32 +/- 7 ml to 28 +/- 5 ml, P < 0.05; PCV, from 31 +/- 2 ml to 26 +/- 4 ml, P < 0.05) decreased. Blood flows to the heart, brain, kidneys and jejunum were maintained. Oxygenation improved and the pulmonary shunt fraction decreased below 10% (HFOV, P < 0.05; PCV, P < 0.05). We detected no differences between HFOV and PCV at comparable transpulmonary pressures. CONCLUSION: A typical recruitment procedure at the initiation of HFOV improved oxygenation but also decreased systemic hemodynamics at high transpulmonary pressures when no changes of vasoactive drugs and fluid management were performed. Blood flow to the organs was not affected during lung recruitment. These effects were independent of the ventilator mode applied.

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We investigated the association between exhaustion and the habituation of free cortisol responses to repeated stress exposure. The study comprised 25 healthy male subjects (38-59 years) who were confronted three times with the Trier Social Stress Test. Mean cortisol responses showed the well-known general habituation effect. A two-way interaction day by exhaustion (p<0.05) indicated that mean cortisol responses vary across stress sessions depending on the extent of exhaustion. Linear regression revealed a negative dose-response relationship between exhaustion and the degree of habituation (p<0.02). We identified 19 individuals showing a response habituation (negative slope) and 6 individuals showing a response sensitization over the three sessions (positive slope) with the latter reporting higher exhaustion scores. It might be hypothesized that impaired habituation to repeated exposure to the same stressor could reflect a state of increased vulnerability for allostatic load. Absence of normal habituation might be one potential mechanism how exhaustion relates to increased disease vulnerability.

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OBJECTIVES: This experiment was performed to evaluate clinically and histologically the effect of mechanical therapy with or without antiseptic therapy on peri-implant mucositis lesions in nine cynomolgus monkeys. MATERIAL AND METHODS: Two ITI titanium implants were inserted into each side of the mandibles. After 90 days of plaque control and soft tissue healing, a baseline clinical examination was completed. Peri-implant lesions were induced by placing silk ligatures and allowing plaque to accumulate for 6 weeks. The clinical examination was then repeated, and the monkeys were randomly assigned to three treatment groups: group A, mechanical cleansing only; group B, mechanical cleansing and local irrigation with 0.12% chlorhexidine (CHX) and application of 0.2% CHX gel; and group C, control, no treatment. The implants in treatment groups A and B were treated and maintained according to the assigned treatment for two additional months. At the end of the maintenance period, a final clinical examination was performed and the animals were sacrificed for biopsies. RESULTS: The mean probing depths (PD) values at mucositis were: 3.5, 3.7, and 3.4 mm, and clinical attachment level (CAL) = 3.8, 4.1, and 3.9 mm for treatment groups A, B and C, respectively. The corresponding values after treatment were: PD = 1.7, 2.1, and 2.5 mm, and CAL=2.6, 2.6, and 3.1 mm. ANOVA of mean changes (Delta) in PD and CAL after treatment showed no statistical difference between the treatment groups. Comparison of the mean changes in PD and CAL after treatment yielded statistical differences between the control and treatment groups P < 0.01. According to the t-test, no statistical difference was found between treatment groups A and B for the PD reduction but there was a significant difference for the CAL change, P < 0.03. Group A had significantly more recession and less CAL gain than group B. Non-parametric tests yielded no significant differences in modified plaque index (mPlI) and gingival index (GI) after treatment between both treatment groups. Frequencies and percent distributions of the mPlI and GI scores changed considerably for both treatment groups when compared with the changes in the control group after treatment. With regard to the histological evaluation, no statistical differences existed between the treatments for any linear measurement. The proportion of inflammation found in the mucosal tissues of the control implants was greater than the one found for both treatment groups, P < 0.01. More importantly, both treatment groups showed a similar low proportion of inflammation after 2 months of treatment. CONCLUSIONS: Within the limitations of this experiment, and considering the supportive plaque control rendered, it can be concluded that for pockets of 3-4 mm: (1) mechanical therapy alone or combined with CHX results in the clinical resolution of peri-implant mucositis lesions, (2) histologically, both treatments result in minimal inflammation compatible with health, and (3) the mechanical effect alone is sufficient to achieve clinical and histologic resolution of mucositis lesions.