Participation of kinin receptors on memory impairment after chronic infusion of human amyloid-beta 1-40 peptide in mice

Chronic infusion of human amyloid-beta 1-40 (A beta) in the lateral ventricle (LV) of rats is associated with memory impairment and increase of kinin receptors in cortical and hippocampal areas. Deletion of kinin B1 or B2 receptors abolished memory impairment caused by an acute single injection of A beta in the LV. As brain tissue and kinin receptors could unlikely react to acute or chronic administration of a similar quantity of A beta, we evaluated the participation of B1 or B2 receptors in memory impairment after chronic infusion of A beta. Male C57BI/6 J (wt), knock-out B1 (koB1) or B2 (koB2) mice (12 weeks of age) previously trained in a two-way shuttle-box and achieving conditioned avoidance responses (CAR, % of 50 trials) were infused with AB (550 pmol, 0.12 mu L/h, 28 days) or vehicle in the LV using a mini-osmotic pump. They were tested before the surgery (TO), 7 and 35 days after the infusion started (T7; T35). In T0, no difference was observed between CAR of the control (Cwt = 59.7 +/- 6.7%; CkoB1 = 46.7 +/- 4.0%; CkoB2 = 64.4 +/- 5.8%) and A beta (A beta wt = 66.0 +/- 3.0%; A beta koB1 = 66.8 +/- 8.2%; A beta koB2 = 58.7 +/- 5.9%) groups. In T7, A beta koB2 showed a significant decrease in CAR (41.0 +/- 8.6%) compared to the control-koB2 (72.8 +/- 2.2%, P <0.05). In T35, a significant decrease (P <0.05) was observed in A beta wt (40.7 +/- 3.3%) and A beta koB2 (41.2 +/- 10.7%) but not in the A beta koB1 (64.0 +/- 14.0%) compared to their control groups. No changes were observed in the controls at T35. We suggest that in chronic infusion of BA, B1 receptors could playan important role in the neurodegenerative process. Conversely, the premature memory impairment of koB2 suggests that it may be a protective factor. (C) 2009 Elsevier Ltd. All rights reserved.

Progeny evaluation for resistance to Phaeosphaeria leaf spot in tropical maize

Maize breeding programmes in Brazil and elsewhere seek reliable methods to identify genotypes resistant to Phaeosphaeria leaf spot. The area under the disease progress curve (AUDPC) is an accurate method to evaluate the severity of foliar diseases. However, at least three data points are required to calculate the AUDPC, which is unfeasible when there are thousands of genotypes to be assessed. The aim of this work was to estimate the heritability of disease resistance, evaluate disease severity at different times using a nine-point scale in comparison to the AUDPC, and establish the most suitable phenological period for disease assessment. A repeated experiment was conducted in a 11 x 11 lattice experimental design with three replications. Disease assessments were carried out at flowering, 15 and 30 days post-anthesis for the parental lines DS95, DAS21, the F1 generation and 118 F2:3 progenies. Then, the AUDPC was obtained and results compared with the single-point evaluations used to calculate it. Individual and joint analyses of variance were conducted to obtain heritabiliy estimates. The assessments performed after the flowering stage gave higher estimates of heritability and correlation with AUDPC. We concluded that one assessment between the 15th and 30th day after flowering could provide enough information to distinguish maize genotypes for their resistance to Phaeosphaeria leaf spot under tropical conditions.

Vegetative and fruit characteristics of papaya trees obtained by mass selection

The present work had as purpose to evaluate some characteristics of papaya trees (Carica papaya L.), Golden cultivar, obtained trough plant mass selection, regarding plant and fruit quality in the first months of production. The samples were evaluated in a commercial crop at: 0, 20, 40, 70, 130, 180, 230, 260, 280, 310 and 340 days after the planting (DAP) and the first fruits were harvested at 230 DAP. The results showed the low height (199cm in 340 DAP) and low first flowering`s heigth (71cm), which is important to facilitate the harvest process. The plants presented good yield with high number of leafs (allowing a great area of fruit cover) and about 60 fruits per plant. The fruits kept similar features to cv. Golden. The fruit`s fresh weight ranged from 302.4 to 467.5g, which is in the range of the Brazilian market. The pulp thickness was 2.35cm, which is a feature of great economic interest. The pulp thickness showed close relation with climatic factors, and great variations of temperature and precipitation accelerated the pulp loss of thickness.

An Apparent Paradox: Attenuation of Phenylephrine-mediated Calcium Mobilization and Hyperreactivity to Phenylephrine in Contralateral Carotid After Balloon Injury

Balloon catheter injury promotes hyperreactivity to phenylephrine (Phe) in the contralateral carotid. Phe-induced contraction involves calcium mobilization, a process that may be sensitive to reactive oxygen species. In this study, we investigated whether increased reactivity to Phe in the contralateral carotid is due to alterations in calcium mobilization by Phe and reactive oxygen species signaling. Concentration-response curves to Phe were obtained in control and contralateral arteries 4 days after balloon injury. Tiron did not modify E(max) to Phe in control arteries but reduced this parameter in the contralateral carotid to control levels. Moreover, immunofluorescence to dihydroethydine showed increased basal oxidative stress in the contralateral artery compared with control artery. Intracellular calcium mobilization by Phe in the contralateral artery was not different from control, but Phe-induced extracellular calcium mobilization was reduced in the contralateral artery compared with that in the control. These data were confirmed by confocal microscopy using Fluo 3-AM. Tiron and SC-236 increased Phe-induced calcium influx in the contralateral artery, which was similar to controls in the same conditions. However, catalase did not modify this response. Taken together, our results suggest that superoxide anions and prostanoids from cyclooxygenase-2 alter pathways downstream of alpha(1)-adrenoceptor activation in the contralateral carotid in response to injury. This results in reduced Phe-induced calcium influx, despite hyperreactivity to Phe.

Evaluation of the Experimental Inoculation of Cryptococcus albidus and Cryptococcus laurentii in Normal Mice: Virulence Factors and Molecular Profile Before and After Animal Passage

The genus Cryptococcus includes free-developing species, a few of which are of medical importance. Some, such as C. neoformans and C. gattii, cause infections in man frequently and C. albidus and C. laurentii cause less so. The aims of this study were to evaluate organ colonization after inoculation of C. albidus and C. laurentii isolates in normal BALB/c mice, the virulence factors (growth at 37A degrees C, capsule, melanin, proteinase, and phospholipase production) and the molecular profile (PCR-fingerprinting) of the yeasts before and after infection. The importance of different profiles (virulence and molecular) was considered in relation to the distribution in different organs and to the time intervals of isolation from organs. C. albidus was isolated from animal organs 2 to 10 days after inoculation and C. laurentii from 2 to 120 days. Most isolates of the two species kept the virulence factors showed before inoculation. The high homogeneity of the molecular profile of C. albidus and the high heterogeneity of C. laurentii were kept through the passages in animals. It is concluded that most isolates of both species were recovered from the animal organs after 5 or more days, and phenotypes were not altered by inoculation. No molecular alteration was detected and the virulence factors were not related to the time intervals before isolation from organs.

Mortality and recurrent cardiac events after coronary artery bypass graft: long term outcomes in a population study

Objective: To determine 30 day mortality, long term survival, and recurrent cardiac events after coronary artery bypass graft (CABG) in a population. Design: Follow up study of patients prospectively entered on to a cardiothoracic surgical database. Record linkages were used to obtain data on readmissions and deaths. Patients: 8910 patients undergoing isolated first CABG between 1980 and 1993 in Western Australia. Main outcome measures: 30 day and long term survival, readmission for cardiac event (acute myocardial infarction, unstable angina, percutaneous transluminal coronary angioplasty or reoperative CABG). Results: There were 3072 deaths to mid 1999. 30 day and long term survival were significantly better in patients treated in the first five years than during the following decade. The age of the patients, proportion of female patients, and number of grafts increased over time. An urgent procedure (odds ratio 3.3), older age (9% per year) and female sex (odds ratio 1.5) were associated with increased risk for 30 day mortality, while age (7% per year) and a recent myocardial infarction (odds ratio 1.16) influenced long term survival. Internal mammary artery grafts were followed by better short and long term survival, though there was an obvious selection bias in favour of younger male patients. Conclusions: This study shows worsening crude mortality at 30 days after CABG from the mid 1980s, associated with the inclusion of higher risk patients. Older age, an acute myocardial infarction in the year before surgery, and the use of sephenous vein grafts only were associated with poorer long term survival and greater risk of a recurrent cardiac event. Female sex predicted recurrent events but not long term survival.

Blockade of vascular smooth muscle cell proliferation and intimal thickening after balloon injury by the sulfated oligosaccharide PI-88: Phosphomannopentaose sulfate directly binds FGF-2, blocks cellular signaling, and inhibits proliferation

Percutaneous transluminal coronary angioplasty is a frequently used interventional technique to reopen arteries that have narrowed because of atherosclerosis. Restenosis, or renarrowing of the artery shortly after angioplasty, is a major limitation to the success of the procedure and is due mainly to smooth muscle cell accumulation in the artery wall at the site of balloon injury. In the present study, we demonstrate that the antiangiogenic sulfated oligosaccharide, PI-88, inhibits primary vascular smooth muscle cell proliferation and reduces intimal thickening 14 days after balloon angioplasty of rat and rabbit arteries. PI-88 reduced heparan sulfate content in the injured artery wall and prevented change in smooth muscle phenotype. However, the mechanism of PI-88 inhibition was not merely confined to the antiheparanase activity of this compound. PI-88 blocked extracellular signal-regulated kinase-1/2 (ERK1/2) activity within minutes of smooth muscle cell injury. It facilitated FGF-2 release from uninjured smooth muscle cells in vitro, and super-released FGF-2 after injury while inhibiting ERK1/2 activation. PI-88 inhibited the decrease in levels of FGF-2 protein in the rat artery wall within 8 minutes of injury. PI-88 also blocked injury-inducible ERK phosphorylation, without altering the clotting time in these animals. Optical biosensor studies revealed that PI-88 potently inhibited (K-i 10.3 nmol/L) the interaction of FGF-2 with heparan sulfate. These findings show for the first time the capacity of this sulfated oligosaccharide to directly bind FGF-2, block cellular signaling and proliferation in vitro, and inhibit injury-induced smooth muscle cell hyperplasia in two animal models. As such, this study demonstrates a new role for PI-88 as an inhibitor of intimal thickening after balloon angioplasty. The full text of this article is available online at http://www.circresaha.org.

Ten-year risk of first recurrent stroke and disability after first-ever stroke in the Perth Community Stroke Study

Background and Purpose-Limited information exists on the long-term prognosis after first-ever stroke. We aimed to determine the absolute frequency of first recurrent stroke and disability and the relative frequency of recurrent stroke over 10 years after first-ever stroke in Perth, Western Australia. Methods-For a 12-month period beginning February 1989, all individuals with suspected acute stroke or transient ischemic attack who lived in a geographically defined and representative region of Perth were registered prospectively. Patients with a definite first-ever stroke were followed up 10 years after the index event. Results-Over 10 years of follow-up, the cumulative risk of a first recurrent stroke was 43% (95% confidence interval [CI], 34 to 51). After the first year after first-ever stroke, the average annual risk of recurrent stroke was approximate to4%. Case fatality at 30 days after first recurrent stroke was 41%, which was significantly greater than the case fatality at 30 days after first-ever stroke (22%) (P=0.003). For 30-day survivors of first-ever stroke, the 10-year cumulative risk of death or new institutionalization was 79% (95% CI, 73 to 85) and of death or new disability was 87% (95% CI, 81 to 92). Conclusions-Over 10 years of follow-up, the risk of first recurrent stroke is 6 times greater than the risk of first-ever stroke in the general population of the same age and sex, almost one half of survivors remain disabled, and one seventh require institutional care. Effective strategies for prevention of stroke need to be implemented early, monitored frequently, and maintained long term after first-ever stroke.

Neuroprotective Effects of Diazepam, Carbamazepine, Phenytoin and Ketamine after Pilocarpine-induced Status Epilepticus

Cell damage and spatial localization deficits are often reported as long-term consequences of pilocarpine-induced status epilepticus. In this study, we investigated the neuroprotective effects of repeated drug administration after long-lasting status epilepticus. Groups of six to eight Wistar rats received microinjections of pilocarpine (2.4 mg/mu l, 1 mu l) in the right dorsal hippocampus to induce a status epilepticus, which was attenuated by thiopental injection (35 mg/kg, i.p.) 3 hrs after onset. Treatments consisted of i.p. administration of diazepam, ketamine, carbamazepine, or phenytoin at 4, 28, 52, and 76 hr after the onset of status epilepticus. Two days after the treatments, rats were tested in the Morris water maze and 1 week after the cognitive tests, their brains were submitted to histology to perform haematoxylin and eosin staining and glial fibrillary acidic protein (GFAP) immunofluorescence detection. Post-status epilepticus rats exhibited extensive gliosis and cell loss in the hippocampal CA1, CA3 (70% cell loss for both areas) and dentate gyrus (60%). Administration of all drugs reduced cell loss in the hippocampus, with best effects observed in brains slices of diazepam-treated animals, which showed less than 30% of loss in the three areas and decreased GFAP immunolabelling. Treatments improved spatial navigation during training trials and probe trial, with exception of ketamine. Interestingly, in the probe trial, only diazepam-treated animals showed preference for the goal quadrant. Our data point to significant neuroprotective effects of repeated administration of diazepam against status epilepticus-induced cell damage and cognitive disturbances.

Residues of spinosad in the tissues of sheep after aerosol treatment of blowfly myiasis

Objective To measure the residues of spinosad and chlorhexidine in the tissues of sheep after treatment of blowfly strike. Procedure Fourteen sheep with natural myiasis and 12 with artificial infestations of Lucilia cuprina larvae had the wool removed over their infestations and were treated with an aerosol wound dressing containing spinosad and chlorhexidine. Sheep were killed up to 14 days after treatment and residues of the chemicals measured in tissues. Results Chlorhexidine was not detected in any tissue. Residues of spinosad were highest in fat, lowest in muscle and intermediate in liver and kidney. The highest residue detected was 0.2 mg/kg spinosad in perirenal fat 7 days after generous treatment of a sheep with a large fly strike. Residues of spinosad in fat peaked 3 to 7 days after treatment and 1 to 3 days after treatment in liver and kidney. Conclusion These studies present a realistic worst-case in struck sheep and at the highest dose studied, equivalent to 5.8 mg spinosad per kg body weight, the maximum residue detected of 0.2 mg/kg in peri-renal fat was 20% of the Australian maximum residue limit. Muscle, liver and kidney residues of spinosad were also below the Australian maximum residue limits at all times.

Rewarded associative and instrumental conditioning after neonatal ventral hippocampus lesions in rats

Sprague Dawley rats were submitted to bilateral ventral hippocampus lesions 7 days after birth. This corresponds to the Lipska and Weinberger`s procedure for modeling schizophrenia. The aim of the present work was to test the learning capacity of such rats with an associative Pavlovian and an instrumental learning paradigm, both methods using reward outcome (food, sucrose or polycose). The associative paradigm comprised also a second learning test with reversed learning contingencies. The instrumental conditioning comprised an extinction test under outcome devaluation conditions. Neonatally lesioned rats, once adults (over 60 days of age), showed a conditioning deficit in the associative paradigm but not in the instrumental one. Lesioned rats remained able to adapt as readily as controls to the reversed learning contingency and were as sensitive as controls to the devaluation of outcome. Such observations indicate that the active access (instrumental learning) to a reward could have compensated for the deficit observed under the ""passive"" stimulus-reward associative learning condition. This feature is compared to the memory management impairments observed in clinical patients. (c) 2008 Elsevier B.V. All rights reserved.

Dizziness after traumatic brain injury: Overview and measurement in the clinical setting

Traumatic brain injury (TBI) may result in a variety of cognitive, behavioural and physical impairments. Dizziness has been reported in up to 80% of cases within the first few days after injury. The literature was reviewed to attempt to delineate prevalence of dizziness as a symptom, impairments causing dizziness, the functional limitations it causes and its measurement. The literature provides widely differing estimates of prevalence and vestibular system dysfunction appears to be the best reported of impairments contributing to this symptom. The variety of results is discussed and other possible causes for dizziness were reviewed. Functional difficulties caused by dizziness were not reported for this population in the literature and review of cognitive impairments suggests that existing measurement tools for dizziness may be problematic in this population. Research on the functional impact of dizziness in the TBI population and measurement of these symptoms appears to be warranted.

Acute increase in urinary 6-sulfatoximelatonin after clomipramine, as a predictive measure for emotional improvement

Nocturnal melatonin pineal output is triggered by sympathetic outflow. Antidepressants that block norepinephrine neuronal uptake should increase pineal function. This can be monitored by measuring 6-sulfatoximelatonin (aMT6s), the main melatonin metabolite, in the urine. In this study, we compared the excretion of aMT6s before (baseline), one, and 21 days after administration of clomipramine to healthy subjects (n = 32). At the end of treatment, subjects were divided into responders (n = 12) and non-responders (n = 20) according to the improvement in their emotional state in three out of four domains (interpersonal tolerance, efficiency, well-being and feeling different from the usual self). There was no difference in aMT6s before clomipramine between responders and non-responders in any of the time intervals analysed (06:00-12:00, 12:00-18:00, 18:00-24:00 and 24:00-06:00 hours). At day one, but not at day 21, the fraction of aMT6s excreted during the time interval 24:00-06:00, relative to the total amount excreted by each subject per day, was significantly higher (P = 0.0287) than baseline (0.57 +/- 0.04) in responders. No significant difference was observed in non-responders. The increase in pineal function induced by clomipramine was restricted to day one, indicating that long-lasting adaptation restores pineal function. In addition, the day one increase in aMT6s was significantly increased only in the responders group, raising the possibility that the blocking of neuronal uptake is predictive of emotional improvement.

Histologic Study of Acute Vocal Fold Wound Healing After Corticosteroid Injection in a Rabbit Model

Objectives: Injectable corticosteroids have been used in phonosurgery to prevent scarring of the vocal fold because of their effects of wound healing, and to ensure better voice quality. We histologically evaluated the effects of dexamethasone sodium phosphate infiltration on acute vocal fold wound healing in rabbits 3 and 7 days after surgically induced injury by quantification of the inflammatory reaction and collagen deposition. Methods: A standardized surgical incision was made in the vocal folds of 12 rabbits, and 0.1 mL dexamethasone sodium phosphate (4 mg/mL) was injected into the left vocal fold. The right vocal fold was not injected and served as the control. The larynges were collected 3 and 7 days after surgery. For histologic analysis, the vocal folds were stained with hematoxylin-eosin for quantification of the inflammatory response and with picrosirius red for qunatification of collagen depostion. Results: There was no quantitative difference in the inflammatory response between vocal folds injected with the corticosteroid and control vocal folds. However, the rate of collage deposition was significantly lower in the corticosteroid-treated group at 3 and 7 days after injury (p = 0.002). Conclusions: The present results suggest that dexamethasone reduces collagen depostion during acute vocal fold wound healing.

Routine abdominal drains after Roux-en-Y gastric bypass: a prospective evaluation of the inflammatory response

Background: Despite the extensive published data regarding the use of drains in surgery, it is still controversial. Most bariatric surgeons use drains as routinely. However, drains have sometimes have been shown to be unhelpful and even to increase the anastomotic leak rates. The purpose of the present study was to evaluate the peritoneal inflammatory response in the presence of a drain left in place until the seventh postoperative day after bariatric surgery. Methods: All patients who underwent open Roux-en-Y gastric bypass from February 2007 to August 2008 were prospectively evaluated. A 24F Blake drain was left in place for 7 days. The peritoneal effluent from the drain was collected for the determination of cytokine levels and for microbiologic analysis. Results: A total of 107 obese patients were studied. A marked increase in the levels of tumor necrosis factor-alpha and interleukin-1 beta was observed by the seventh postoperative day, even in patients without any abdominal complications. Bacterial contamination of the peritoneal effluent was also demonstrated. Conclusion: The results of our study have shown that at 7 days after surgery, a marked peritoneal inflammatory response and bacterial contamination are present. These findings could have resulted from the use of the drain for 7 postoperative days. (Surg Obes Relat Dis 2010;6:648-652.) (C) 2010 American Society for Metabolic and Bariatric Surgery. All rights reserved.