Effects of a dexmedetomidine constant rate infusion and atropine on changes in global perfusion variables induced by hemorrhage followed by volume replacement in isoflurane-anesthetized dogs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of different periods of estrogen replacement onset in the tibia of ovariectomized rats

Background and aims Estrogen deficiency results in increased bone turnover and can lead to osteoporosis. Hormone replacement therapy (HRT) seems to be the most effective means of reducing bone loss and fractures. However, the effects of the period of HRT onset on bone tissue require further elucidation. This study aimed to evaluate the effects of different periods of HRT onset on the trabecular bone of ovariectomized rats.Methods Seventy-five ovariectomized Wistar rats were divided into five groups according to the onset of treatment. Each group was subdivided into experimental (E; n = 10) and control (C; n = 5), according to treatment with 17-beta-estradiol or vehicle alone (soybean oil), respectively, administered subcutaneously. The first group received treatment immediately post-surgery, while treatment in the remaining groups was initiated 1, 2, 3 and 4 weeks post-surgery. Euthanasia occurred at 9 weeks post-surgery. The left tibias were removed and prepared for histomorphometric analyses. The histomorphometric results were statistically analyzed by the Student's t test (p < 0.05).Results The percentage of trabecular bone was significantly greater in the first (p = 0.002) and second (p = 0.039) experimental subgroups compared with the control for the same period. In the experimental subgroups, the percentage of trabecular bone decreased according to the delay in HRT onset and was statistically significant (t = 3.367; p = 0.0023).Conclusion These findings indicate an increase in trabecular bone loss in tibia at 9 weeks post-ovariectomy. The period of HRT/E onset is important for preventing bone loss; however, despite its preventive effects, HRT/E does not restore lost bone.

Effects of castration and of testosterone replacement on alpha(1)-adrenoceptor subtypes in the rat vas deferens

The contractions of the rat vas deferens in response to noradrenaline are mediated through alpha(1A)-adrenoceptors. We observed participation of alpha(1B)-adrenoceptors in these contractions after castration. We now investigated the time course of this plasticity and the effects of testosterone by determining the actions of competitive antagonists on noradrenaline-induced contractions after 7, 14, 21 and 30 days of castration. BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) antagonised noradrenaline-induced contractions in control and castrated rats with low pA(2) values (approximately = 6.8). In control vas deferens, WB 4101 (2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane hydrochloride) had a slope in the Schild plot no different from 1.0, while slopes lower than 1.0 (approximately 0.6) were observed for vas deferens from castrated rats. Chloroethylclonidine was ineffective in the control vas while it inhibited noradrenaline-induced contractions in vasa from castrated rats and converted the complex antagonism by WB 4101 into simple competitive antagonism. Treatment of castrated rats with testosterone prevented the effects of castration. The results suggest that alpha(1B)-adrenoceptors are detectable in vas deferens from at least the 7th through the 30th day after castration and that testosterone prevents this plasticity.

Seal, replacement or monitoring amalgam restorations with occlusal marginal defects? Results of a 10-year clinical trial

The aim of this prospective and blind clinical trial was to assess the effectiveness of sealing localized marginal defects of amalgam restoration that were initially scheduled to be replaced. A cohort of twenty six patients with 60 amalgam restorations (n=44Class I and n=16Class II), that presented marginal defects deviating from ideal (Bravo) according to USPHS criteria, were assigned to either sealing or replacement groups: A: sealing n=20, Replacement n=20, and no treatment (n=20). Two blind examiners evaluated the restorations at baseline (K=0.74) and after ten years (K=0.84) according with USPHS criteria, in four parameters: marginal adaptation (MA), secondary caries (SC), marginal staining (MS) and teeth sensitivity (TS). Multiple comparison of restorations degradation/upgrade was analyzed by Friedman test and the comparisons within groups were performed by Wilcoxon test. After 10 years, 44 restorations were assessed (73.3%), Group A: n=14 and Group B: n=16; and Group C: n=14 sealing and replacement amalgam restorations presented similar level of quality in MA (p=0.76), SC (p=0.25) and TS (p=0.52), while in MS (p=0.007) presented better performance in replacement group after 10-years. Most of the occlusal amalgam restorations with marginal gaps showed similar long term outcomes than the restorations were sealed, replaced, or not treated over a 10-year period. Most of the restorations of the three groups were clinically acceptable, under the studied parameters. All restorations had the tendency to present downgrade/deterioration over time.

Evidence for temporal population replacement and the signature of ecological adaptation in a major Neotropical malaria vector in Amazonian Peru

The major Neotropical malaria vector, Anopheles darlingi, was reintroduced into the Iquitos, Loreto, Peru area during the early 1990s, where it displaced other anophelines and caused a major malaria epidemic. Since then, case numbers in Loreto have fluctuated, but annual increases have been reported since 2012. The population genetic structure of An. darlingi sampled before and after the introduction of long-lasting insecticidal nets (LLINs) was investigated to test the hypothesis of temporal population change (2006 vs. 2012). Current samples of An. darlingi were used to test the hypothesis of ecological adaptation to human modified (highway) compared with wild (riverine) habitat, linked to forest cover. In total, 693 An. darlingi from nine localities in Loreto, Peru area were genotyped using 13 microsatellite loci. To test the hypothesis of habitat differentiation in An. darlingi biting time patterns, HBR and EIR, four collections of An. darlingi from five localities (two riverine and three highway) were analysed. Analyses of microsatellite loci from seven (2006) and nine settlements (2012-2014) in the Iquitos area detected two distinctive populations with little overlap, although it is unclear whether this population replacement event is associated with LLIN distribution or climate. Within the 2012-2014 population two admixed subpopulations, A and B, were differentiated by habitat, with B significantly overrepresented in highway, and both in near-equal proportions in riverine. Both subpopulations had a signature of expansion and there was moderate genetic differentiation between them. Habitat and forest cover level had significant effects on HBR, such that Plasmodium transmission risk, as measured by EIR, in peridomestic riverine settlements was threefold higher than in peridomestic highway settlements. HBR was directly associated with available host biomass rather than forest cover. A population replacement event occurred between 2006 and 2012-2014, concurrently with LLIN distribution and a moderate El Niño event, and prior to an increase in malaria incidence. The likely drivers of this replacement cannot be determined with current data. The present-day An. darlingi population is composed of two highly admixed subpopulations, which appear to be in an early stage of differentiation, triggered by anthropogenic alterations to local habitat.

Tailoring the structure, composition, optical properties and catalytic activity of Ag-Au nanoparticles by the galvanic replacement reaction

This Letter reports on the synthesis of Ag-Au nanoparticles (NPs) with controlled structures and compositions via a galvanic replacement reaction between Ag NPs and AuCl4(aq)- followed by the investigation of their optical and catalytic properties. Our results showed the formation of porous walls, hollow interiors and increased Au content in the Ag-Au NPs as the volume of AuCl4(aq)- employed in the reaction was increased. These variations led to a red shift and broadening of the SPR peaks and an increase of up to 10.9-folds in the catalytic activity towards the reduction of 4-nitrophenol relative to Ag NPs. (C) 2012 Elsevier B.V. All rights reserved.

Replacement of fentanyl infusion by enteral methadone decreases the weaning time from mechanical ventilation: a randomized controlled trial

Introduction: Patients undergoing mechanical ventilation (MV) are frequently administered prolonged and/or high doses of opioids which when removed can cause a withdrawal syndrome and difficulty in weaning from MV. We tested the hypothesis that the introduction of enteral methadone during weaning from sedation and analgesia in critically ill adult patients on MV would decrease the weaning time from MV. Methods: A double-blind randomized controlled trial was conducted in the adult intensive care units (ICUs) of four general hospitals in Brazil. The 75 patients, who met the criteria for weaning from MV and had been using fentanyl for more than five consecutive days, were randomized to the methadone (MG) or control group (CG). Within the first 24 hours after study enrollment, both groups received 80% of the original dose of fentanyl, the MG received enteral methadone and the CG received an enteral placebo. After the first 24 hours, the MG received an intravenous (IV) saline solution (placebo), while the CG received IV fentanyl. For both groups, the IV solution was reduced by 20% every 24 hours. The groups were compared by evaluating the MV weaning time and the duration of MV, as well as the ICU stay and the hospital stay. Results: Of the 75 patients randomized, seven were excluded and 68 were analyzed: 37 from the MG and 31 from the CG. There was a higher probability of early extubation in the MG, but the difference was not significant (hazard ratio: 1.52 (95% confidence interval (CI) 0.87 to 2.64; P = 0.11). The probability of successful weaning by the fifth day was significantly higher in the MG (hazard ratio: 2.64 (95% CI: 1.22 to 5.69; P < 0.02). Among the 54 patients who were successfully weaned (29 from the MG and 25 from the CG), the MV weaning time was significantly lower in the MG (hazard ratio: 2.06; 95% CI 1.17 to 3.63; P < 0.004). Conclusions: The introduction of enteral methadone during weaning from sedation and analgesia in mechanically ventilated patients resulted in a decrease in the weaning time from MV.

Central leptin replacement enhances chemorespiratory responses in leptin-deficient mice independent of changes in body weight

Previous studies showed that leptin-deficient (ob/ob) mice develop obesity and impaired ventilatory responses to CO2 . In this study, we examined if leptin replacement improves chemorespiratory responses to hypercapnia (7 % CO2) in ob/ob mice and if these effects were due to changes in body weight or to the direct effects of leptin in the central nervous system (CNS). was measured via plethysmography in obese leptin-deficient- (ob/ob) and wild-type- (WT) mice before and after leptin (10 mu g/2 mu l day) or vehicle (phosphate buffer solution) were microinjected into the fourth ventricle for four consecutive days. Although baseline was similar between groups, obese ob/ob mice exhibited attenuated compared to WT mice (134 +/- 9 versus 196 +/- 10 ml min(-1)). Fourth ventricle leptin treatment in obese ob/ob mice significantly improved (from 131 +/- 15 to 197 +/- 10 ml min(-1)) by increasing tidal volume (from 0.38 +/- 0.03 to 0.55 +/- 0.02 ml, vehicle and leptin, respectively). Subcutaneous leptin administration at the same dose administered centrally did not change in ob/ob mice. Central leptin treatment in WT had no effect on . Since the fourth ventricle leptin treatment decreased body weight in ob/ob mice, we also examined in lean pair-weighted ob/ob mice and found it to be impaired compared to WT mice. Thus, leptin deficiency, rather than obesity, is the main cause of impaired in ob/ob mice and leptin appears to play an important role in regulating chemorespiratory response by its direct actions on the CNS.

Retrospective Clinical Study of 988 Dual Acid-Etched Implants Placed in Grafted and Native Bone for Single-Tooth Replacement

Purpose: To evaluate the influence of sex, implant characteristics, and bone grafting on the survival rate of dual acid-etched (DAE) implants. Materials and Methods: Patients treated with internal-hex DAE implants for single-tooth replacement in a military dental clinic between January 2005 and December 2010 were included in this study. Clinical data related to implant characteristics, implant location, presence of grafted bone, and implant failures were collected. The primary outcome was implant loss. The survival rate was analyzed using the Kaplan-Meier method. Cox regression modeling was used to determine which factors would predict implant failure. Results: DAE implants were evaluated in a total of 988 patients (80.3% men). Twenty-four (2.4%) implants failed, most were cylindric (54.2%) with regular platforms (70.8%) and were 10 mm long (58.3%). The failure rate was 2.4% for the anterior maxilla, 3.3% for the posterior maxilla, 1.6% for the anterior mandible, and 2.0% for posterior mandible. The cumulative survival rate was 97.6%. The failure rate was 8.8% in implants placed after sinus augmentation, 7.3% in bone block-grafted areas, and 1.6% in native bone. Based on multivariable analysis (Cox regression), sinus augmentation and bone block grafting had a statistically significant effect on implant failure; the hazard ratios were 5.5 and 4.6, respectively. Conclusion: The results revealed that DAE implants had high survival rates, and no influence of sex, location, shape, diameter, or length on failure rates could be observed. However, a significant association was observed between failure and presence of bone graft in the implant area. Int J Oral Maxillofac Implants 2012;27:1243-1248

Partial Replacement of omega-6 Fatty Acids With Medium-Chain Triglycerides, but Not Olive Oil, Improves Colon Cytokine Response and Damage in Experimental Colitis

Background: Soybean oil is rich in omega-6 fatty acids, which are associated with higher incidence and more severe cases of inflammatory bowel diseases. The authors evaluated whether partial replacement of soybean oil by medium-chain triglycerides (MCTs) or olive oil influenced the incidence and severity of experimental ulcerative colitis by using different parenteral lipid emulsions (LEs). Methods: Wistar rats (n = 40) were randomized to receive parenteral infusion of the following LE: 100% soybean oil (SO), 50% MCT mixed with 50% soybean oil (MCT/SO), 80% olive oil mixed with 20% soybean oil (OO/SO), or saline (CC). After 72 hours of infusion, acetic acid experimental colitis was induced. After 24 hours, colon histology and cytokine expression were analyzed. Results: SO was not significantly associated with overall tissue damage. MCT/SO was not associated with necrosis (P < .005), whereas OO/SO had higher frequencies of ulcer and necrosis (P < .005). SO was associated with increased expression of interferon-gamma (P = .005) and OO/SO with increased interleukin (IL)-6 and decreased tumor necrosis factor-alpha expression (P < .05). MCT/SO appeared to decrease IL-1 (P < .05) and increase IL-4 (P < .001) expression. Conclusions: Parenteral SO with high concentration of omega-6 fatty acids was not associated with greater tissue damage in experimental colitis. SO partial replacement with MCT/SO decreased the frequency of histological necrosis and favorably modulated cytokine expression in the colon; however, replacement with OO/SO had unfavorable effects. (JPEN J Parenter Enteral Nutr. 2012; 36: 442-448)

17 beta-Estradiol replacement in young, adult and middle-aged female ovariectomized rats promotes improvement of spatial reference memory and an antidepressant effect and alters monoamines and BDNF levels in memory- and depression-related brain areas

Clinical and experimental evidence suggest that estrogens have a major impact on cognition, presenting neurotrophic and neuroprotective actions in regions involved in such function. In opposite, some studies indicate that certain hormone therapy regimens may provoke detrimental effects over female cognitive and neurological function. Therefore, we decided to investigate how estrogen treatment would influence cognition and depression in different ages. For that matter, this study assessed the effects of chronic 17 beta-estradiol treatment over cognition and depressive-like behaviors of young (3 months old), adult (7 months old) and middle-aged (12 months old) reproductive female Wistar rats. These functions were also correlated with alterations in the serotonergic system, as well as hippocampal BDNF. 17 beta-Estradiol treatment did not influence animals' locomotor activity and exploratory behavior, but it was able to improve the performance of adult and middle-aged rats in the Morris water maze, the latter being more responsive to the treatment. Young and adult rats displayed decreased immobility time in the forced swimming test, suggesting an effect of 17 beta-estradiol also over such depressive-like behavior. This same test revealed increased swimming behavior, triggered by serotonergic pathway, in adult rats. Neurochemical evaluations indicated that 17 beta-estradiol treatment was able to increase serotonin turnover rate in the hippocampus of adult rats. Interestingly, estrogen treatment increased BDNF levels from animals of all ages. These findings support the notion that the beneficial effects of 17 beta-estradiol over spatial reference memory and depressive-like behavior are evident only when hormone therapy occurs at early ages and early stages of hormonal decline. (C) 2011 Elsevier B.V. All rights reserved.

Expression of VEGF and collagen using a latex biomembrane as bladder replacement in rabbits

Objective: To investigate the VEGF expression and collagen deposition using a latex biomembrane as bladder replacement in rabbits. Materials and Methods: After partial cystectomy, a patch of a non-vulcanized latex biomembrane (2 x 2 cm) was sewn to the bladder of rabbits with 5/0 monofilament polydioxanone sulfate sutures in a watertight manner. Groups of 5 animals were killed at 15, 45 and 90 days after surgery and the bladder was removed. Sections of 5 mu m were cut and stained with picrosirius-red in order to estimate the amount of extracellular matrix in the graft. To confirm the presence of VEGF in tissues, protein expression was determined by immunohistochemistry. Results: No death, urinary leakage or graft extrusion occurred in any group. All bladders showed a spherical shape. A progressive reduction in the amount of collagen occurred in the graft area and was negatively and linearly correlated with time (p < 0.001). VEGF expression was higher in grafted areas when compared to controls at 15 and 45 days after surgery and decreased with time (p < 0.001). Conclusion: The latex biomembrane as a matrix for partial bladder replacement in rabbits promotes temporary collagen deposition and stimulates the angiogenic process.

Small volume of hypertonic saline as the initial fluid replacement in experimental hypodynamic sepsis

Abstract Introduction We conducted the present study to examine the effects of hypertonic saline solution (7.5%) on cardiovascular function and splanchnic perfusion in experimental sepsis. Methods Anesthetized and mechanically ventilated mongrel dogs received an intravenous infusion of live Escherichia coli over 30 minutes. After 30 minutes, they were randomized to receive lactated Ringer's solution 32 ml/kg (LR; n = 7) over 30 minutes or 7.5% hypertonic saline solution 4 ml/kg (HS; n = 8) over 5 minutes. They were observed without additional interventions for 120 minutes. Cardiac output (CO), mean arterial pressure (MAP), portal and renal blood flow (PBF and RBF, respectively), gastric partial pressure of CO2 (pCO2; gas tonometry), blood gases and lactate levels were assessed. Results E. coli infusion promoted significant reductions in CO, MAP, PBF and RBF (approximately 45%, 12%, 45% and 25%, respectively) accompanied by an increase in lactate levels and systemic and mesenteric oxygen extraction (sO2ER and mO2ER). Widening of venous-arterial (approximately 15 mmHg), portal-arterial (approximately 18 mmHg) and gastric mucosal-arterial (approximately 55 mmHg) pCO2 gradients were also observed. LR and HS infusion transiently improved systemic and regional blood flow. However, HS infusion was associated with a significant and sustained reduction of systemic (18 ± 2.6 versus 38 ± 5.9%) and mesenteric oxygen extraction (18.5 ± 1.9 versus 36.5 ± 5.4%), without worsening other perfusional markers. Conclusion A large volume of LR or a small volume of HS promoted similar transient hemodynamic benefits in this sepsis model. However, a single bolus of HS did promote sustained reduction of systemic and mesenteric oxygen extraction, suggesting that hypertonic saline solution could be used as a salutary intervention during fluid resuscitation in septic patients.

New functional and biomechanical assessments for the improvement of the surgical navigation systems for joint replacement in the human lower limb

In case of severe osteoarthritis at the knee causing pain, deformity, and loss of stability and mobility, the clinicians consider that the substitution of these surfaces by means of joint prostheses. The objectives to be pursued by this surgery are: complete pain elimination, restoration of the normal physiological mobility and joint stability, correction of all deformities and, thus, of limping. The knee surgical navigation systems have bee developed in computer-aided surgery in order to improve the surgical final outcome in total knee arthroplasty. These systems provide the surgeon with quantitative and real-time information about each surgical action, like bone cut executions and prosthesis component alignment, by mean of tracking tools rigidly fixed onto the femur and the tibia. Nevertheless, there is still a margin of error due to the incorrect surgical procedures and to the still limited number of kinematic information provided by the current systems. Particularly, patello-femoral joint kinematics is not considered in knee surgical navigation. It is also unclear and, thus, a source of misunderstanding, what the most appropriate methodology is to study the patellar motion. In addition, also the knee ligamentous apparatus is superficially considered in navigated total knee arthroplasty, without taking into account how their physiological behavior is altered by this surgery. The aim of the present research work was to provide new functional and biomechanical assessments for the improvement of the surgical navigation systems for joint replacement in the human lower limb. This was mainly realized by means of the identification and development of new techniques that allow a thorough comprehension of the functioning of the knee joint, with particular attention to the patello-femoral joint and to the main knee soft tissues. A knee surgical navigation system with active markers was used in all research activities presented in this research work. Particularly, preliminary test were performed in order to assess the system accuracy and the robustness of a number of navigation procedures. Four studies were performed in-vivo on patients requiring total knee arthroplasty and randomly implanted by means of traditional and navigated procedures in order to check for the real efficacy of the latter with respect to the former. In order to cope with assessment of patello-femoral joint kinematics in the intact and replaced knees, twenty in-vitro tests were performed by using a prototypal tracking tool also for the patella. In addition to standard anatomical and articular recommendations, original proposals for defining the patellar anatomical-based reference frame and for studying the patello-femoral joint kinematics were reported and used in these tests. These definitions were applied to two further in-vitro tests in which, for the first time, also the implant of patellar component insert was fully navigated. In addition, an original technique to analyze the main knee soft tissues by means of anatomical-based fiber mappings was also reported and used in the same tests. The preliminary instrumental tests revealed a system accuracy within the millimeter and a good inter- and intra-observer repeatability in defining all anatomical reference frames. In in-vivo studies, the general alignments of femoral and tibial prosthesis components and of the lower limb mechanical axis, as measured on radiographs, was more satisfactory, i.e. within ±3°, in those patient in which total knee arthroplasty was performed by navigated procedures. As for in-vitro tests, consistent patello-femoral joint kinematic patterns were observed over specimens throughout the knee flexion arc. Generally, the physiological intact knee patellar motion was not restored after the implant. This restoration was successfully achieved in the two further tests where all component implants, included the patellar insert, were fully navigated, i.e. by means of intra-operative assessment of also patellar component positioning and general tibio-femoral and patello-femoral joint assessment. The tests for assessing the behavior of the main knee ligaments revealed the complexity of the latter and the different functional roles played by the several sub-bundles compounding each ligament. Also in this case, total knee arthroplasty altered the physiological behavior of these knee soft tissues. These results reveal in-vitro the relevance and the feasibility of the applications of new techniques for accurate knee soft tissues monitoring, patellar tracking assessment and navigated patellar resurfacing intra-operatively in the contest of the most modern operative techniques. This present research work gives a contribution to the much controversial knowledge on the normal and replaced of knee kinematics by testing the reported new methodologies. The consistence of these results provides fundamental information for the comprehension and improvements of knee orthopedic treatments. In the future, the reported new techniques can be safely applied in-vivo and also adopted in other joint replacements.