Can the `yin and yang` BDNF hypothesis be used to predict the effects of rTMS treatment in neuropsychiatry?

Repetitive transcranial magnetic stimulation (rTMS) is a novel technique of non-invasive brain stimulation which has been used to treat several neuropsychiatric disorders such as major depressive disorder, chronic pain and epilepsy. Recent studies have shown that the therapeutic effects of rTMS are associated with plastic changes in local and distant neural networks. In fact, it has been suggested that rTMS induces long-term potentiation (LTP) and long-term depression (LTD) - like effects. Besides the initial positive clinical results; the effects of rTMS are stilt mixed. Therefore new toots to assess the effects of plasticity non-invasively might be useful to predict its therapeutic effects and design novel therapeutic approaches using rTMS. In this paper we propose that brain-derived neurotrophic factor (BDNF) might be such a tool. Brain-derived neurotrophic factor is a neurotrophin that plays a key role in neuronal survival and synaptic strength, which has also been studied in several neuropsychiatric disorders. There is robust evidence associating BDNF with the LTP/LTD processes, and indeed it has been proposed that BNDF might index an increase or decrease of brain activity - the `yin and yang` BDNF hypothesis. In this article, we review the initial studies combining measurements of BDNF in rTMS clinical trials and discuss the results and potential usefulness of this instrument in the field of rTMS. (C) 2008 Elsevier Ltd. All rights reserved.

H-1 low- and high-field NMR study of the effects of plasma treatment on the oil and water fractions in crude heavy oil

The chemical and physical properties of a Brazilian heavy oil submitted to plasma treatment were investigated by H-1 low-and high-field nuclear magnetic resonance (NMR) combined to the characterization of rheological properties, thermogravimetry and measurement of basic sediments and water (BSW) content. The crude oil was treated in a dielectric barrier discharge plasma reactor, using natural gas, CO2 or H-2 as working gas. The results indicated a large drop in the water content of the plasma-treated samples as compared to the crude oil, giving rise to a reduction in the viscosity. No significant chemical change was produced in the oil portion itself, as observed by H-1 NMR. The water contents determined by H-1 low-field NMR analyses agreed well with those obtained by BSW, indicating the low-field NMR methods as a useful tool for following the effects of plasma treatments on heavy oils, allowing the separation of the effects caused on the water and oil fractions. (C) 2011 Elsevier Ltd. All rights reserved.

In Vitro Effects of Bevacizumab Treatment on Newborn Rat Retinal Cell Proliferation, Death, and Differentiation

PURPOSE. Vascular endothelial growth factor (VEGF) is an important signal protein in vertebrate nervous development, promoting neurogenesis, neuronal patterning, and glial cell growth. Bevacizumab, an anti-VEGF agent, has been extensively used for controlling pathological retinal neovascularization in adult and newborn patients, although its effect on the developing retina remains largely unknown. The purpose of this study was to investigate the effect of bevacizumab on cell death, proliferation, and differentiation in newborn rat retina. METHODS. Retinal explants of sixty 2-day-old Lister hooded rats were obtained after eye enucleation and maintained in culture media with or without bevacizumab for 2 days. Immunohistochemical staining was assessed against proliferating cell nuclear antigen (PCNA, to detect cell proliferation); caspase-3 and beclin-1 (to investigate cell death); and vimentin and glial fibrillary acidic protein (GFAP, markers of glial cells). Gene expressions were quantified by real-time reverse-transcription polymerase chain reaction. Results from treatment and control groups were compared. RESULTS. No significant difference in the staining intensity (on immunohistochemistry) of PCNA, caspase-3, beclin-1, and GFAP, or in the levels of PCNA, caspase-3, beclin-1, and vimentin mRNA was observed between the groups. However, a significant increase in vimentin levels and a significant decrease in GFAP mRNA expression were observed in bevacizumab-treated retinal explants compared with controls. CONCLUSIONS. Bevacizumab did not affect cell death or proliferation in early developing rat retina but appeared to interfere with glial cell maturation by increasing vimentin levels and downregulating GFAP gene expression. Thus, we suggest anti-VEGF agents be used with caution in developing retinal tissue. (Invest Ophthalmol Vis Sci. 2012;53:7904-7911) DOI:10.1167/iovs.12-10283

Association of a probiotic to a Helicobacter pylori eradication regimen does not increase efficacy or decreases the adverse effects of the treatment: a prospective, randomized, double-blind, placebo-controlled study

Abstract Background The treatment for the eradication of Helicobacter pylori (H. pylori) is complex; full effectiveness is rarely achieved and it has many adverse effects. In developing countries, increased resistance to antibiotics and its cost make eradication more difficult. Probiotics can reduce adverse effects and improve the infection treatment efficacy. If the first-line therapy fails a second-line treatment using tetracycline, furazolidone and proton-pump inhibitors has been effective and low cost in Brazil; however it implies in a lot of adverse effects. The aim of this study was to minimize the adverse effects and increase the eradication rate applying the association of a probiotic compound to second-line therapy regimen. Methods Patients with peptic ulcer or functional dyspepsia infected by H. pylori were randomized to treatment with the furazolidone, tetracycline and lansoprazole regimen, twice a day for 7 days. In a double-blind study, patients received placebo or a probiotic compound (Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum and Streptococcus faecium) in capsules, twice a day for 30 days. A symptom questionnaire was administered in day zero, after completion of antibiotic therapy, after the probiotic use and eight weeks after the end of the treatment. Upper digestive endoscopy, histological assessment, rapid urease test and breath test were performed before and eight weeks after eradication treatment. Results One hundred and seven patients were enrolled: 21 men with active probiotic and 19 with placebo plus 34 women with active probiotic and 33 with placebo comprising a total of 55 patients with active probiotic and 52 with placebo. Fifty-one patients had peptic ulcer and 56 were diagnosed as functional dyspepsia. The per-protocol eradication rate with active probiotic was 89.8% and with placebo, 85.1% (p = 0.49); per intention to treat, 81.8% and 79.6%, respectively (p = 0.53). The rate of adverse effects at 7 days with the active probiotic was 59.3% and 71.2% with placebo (p = 0.20). At 30 days, it was 44.9% and 60.4%, respectively (p = 0.08). Conclusions The use of this probiotic compound compared to placebo in the proposed regimen in Brazilian patients with peptic ulcer or functional dyspepsia showed no significant difference in efficacy or adverse effects. Trial registration Current Controlled Trials ISRCTN04714018

Late Adverse Effects of the Coadministration of Valproate and Lamotrigine

Individuals treated with combined valproate-lamotrigine rarely present late adverse effects (unrelated to introduction and titration). We describe four patients in whom such effects occurred after continuous, long-term use of valproate-lamotrigine (at 9 months to 2 years after final antiepileptic drug adjustment). The patients presented heterogeneous disturbances, including ataxia, vertigo, and headache, and rare movement disorders, such as tics and abnormal eye movements. Although these effects are heterogeneous in their occurrence and timing, they can alert physicians to the possibility of late neurologic disturbances, and must be considered in order to avoid unnecessary ancillary tests. Treatment discontinuation is unnecessary, given that a small decrease in dose led to remission of these adverse effects. (c) 2012 Elsevier Inc. All rights reserved.

Late evaluation of the relationship between morphological and functional renal changes and hypertension after non-operative treatment of high-grade renal injuries

Objective: To evaluate the anatomical and functional renal alterations and the association with post-traumatic arterial hypertension. Methods: The studied population included patients who sustained high grades renal injury (grades III to V) successfully non-operative management after staging by computed tomography over a 16-year period. Beyond the review of medical records, these patients were invited to the following protocol: clinical and laboratory evaluation, abdominal computed tomography, magnetic resonance angiography, DMSA renal scintigraphy, and ambulatory blood pressure monitoring. The hypertensive patients also were submitted to dynamic renal scintigraphy (Tc-99m EC), using captopril stimulation to verify renal vascular etiology. Results: Of the 31 patients, there were thirteen grade III, sixteen grade IV (nine lacerations, and seven vascular lesions), and two grade V injuries. All the patients were asymptomatic and an average follow up post-injury of 6.4 years. None had abnormal BUN or seric creatinine. The percentage of renal volume reduction correlates with the severity as defined by OIS. There was no evidence of renal artery stenosis in Magnetic Resonance angiography (MRA). DMSA scanning demonstrated a decline in percentage of total renal function corresponding to injury severity (42.2 +/- 5.5% for grade III, 35.3 +/- 12.8% for grade IV, 13.5 +/- 19.1 for grade V). Six patients (19.4%) had severe compromised function (< 30%). There was statistically significant difference in the decrease in renal function between parenchymal and vascular causes for grade IV injuries (p < 0.001). The 24-hour ambulatory blood pressure monitoring detected nine patients (29%) with post-traumatic hypertension. All the patients were male, mean 35.6 years, 77.8 % had a familial history of arterial hypertension, 66.7% had grade III renal injury, and average post-injury time was 7.8 years. Seven patients had negative captopril renography. Conclusions: Late results of renal function after conservative treatment of high grades renal injuries are favorable, except for patients with grades IV with vascular injuries and grade V renal injuries. Moreover, arterial hypertension does not correlate with the grade of renal injury or reduction of renal function.

Effects of exogenous calcium or oxalic acid on Pinus taeda treatment with the white-rot fungus Ceriporiopsis subvermispora

Pinus taeda wood chips were treated with the biopulping fungus Ceriporiopsis subvermispora in calcium-or oxalic acid-amended cultures. The secretion of hydrolytic and oxidative enzymes was inhibited only in the cultures having the highest concentration of calcium (1400 mg kg(-1) wood). Calcium decreased the availability of free oxalic acid, inhibited fungal growth, and reduced lignin mineralization and transformations. Oxalic acid amendment in the cultures was found not to affect the lignin mineralization and transformations; however, it did inhibit the depolymerization reactions detectable in the residual lignin that was retained in the biotreated wood. C. subvermispora presented catabolic activity for oxalic acid in the cultures amended with 1660 mg acid kg(-1) wood, whereas oxalic acid was synthesized when it was amended at low amounts or initially absent in the cultures. These data suggest one ideal ratio of oxalic acid in C. subvermispora cultures and indicate that its exogenous addition does not necessarily accompany the further degradation of lignin. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.

Effects of 3-Dimensional Conformal or Intensity-modulated Radiotherapy on Dental Pulp Sensitivity during and after the Treatment of Oral or Oropharyngeal Malignancies

Introduction: Radiation therapy (RT) of malignant tumors in the head and neck area may have damaging effects on surrounding tissues. The aim of this investigation was to evaluate the effects of RI delivered by 3-dimensional conformal radiotherapy (3D-RT) or intensity-modulated radiotherapy (IMRT) on dental pulp sensitivity. Methods: Twenty patients with oral or oropharyngeal cancer receiving RT with 3D-RT or IMRT underwent cold thermal pulp sensitivity testing (PST) of 2 teeth each at 4 time points: before RT (TP1), the beginning of RT with doses between 30 and 35 Gy (TP2), the end of RT with doses between 60 and 70 Gy (TP3), and 4 to 5 months after the start of RT (TP4). Results: All 40 teeth showed positive responses to PST at TP1 (100%) and 9 at TP2 (22.5%; 3/16 [18.8%] for 3D-RT and 6/24 [25.0%] for IMRT). No tooth responded to PST at TP3 and TP4 (0%). A statistically significant difference existed in the number of positive pulp responses between different time points (TP1 through TP4) for all patients receiving RT (P <= .05), IMRT (P <= .05), and 3D-RT (P <= .05). No statistically significant differences in positive sensitivity responses were found between 3D-RT and IMRT at any time point (TP1, TP3, TP4, P = 1.0; TP2, P = .74). A statistically significant correlation existed between the location of the tumor and PST at TP2 for IMRT (P <= .05) but not for 3D-RT (P = .14). Conclusions: RT decreased the number of teeth responding to PST after doses greater than 30 to 35 Gy. The type of RT (3D-RT or IMRT) had no influence on the pulp responses to PST after the conclusion of RT. (J Endod 2012;38:148-152)

Field and laboratory studies to assess the effects of Vertimec (R) 18EC on Daphnia similis

The present study aimed to evaluate the interactions of the pesticide Vertimec (R) 18EC in aquatic ecosystems. In this respect, soil plots were contaminated with Vertimec (R) 18EC at the concentration indicated for strawberry crops (0.125 L of solution m(-2)). After the contamination, torrential rainfall was simulated and the surface runoff was collected and transferred to mesocosm tanks in five treatments, run in triplicate: (1) control-C; (2) runoff from an uncontaminated plot-UR; (3) runoff from the plot contaminated with Vertimec (R) 18EC-CR; (4) direct application of Vertimec (R) 18EC in the water-V and (5) water samples gathered randomly to verify whether there was contamination between the mesocosms-RS. Water samples from these tanks were also submitted to ecotoxicological tests with Daphnia similis and analyses to evaluate the limnological characteristics, in five collection periods over 10 days (240 h). Physical and chemical differences were observed in the water samples, mainly related to increased turbidity, suspended solids and nutrients (nitrogen and phosphate forms). Acute toxicity was observed for the direct application treatment for the entire experimental period, and in some periods for the CR treatment (from 48 h to 168 h). The results obtained suggest that the pesticide did not fully degrade during the study period (10 days) in the direct application treatment, demonstrating that the presence of other substances in the commercial formulation contribute to the maintenance of toxicity. This represents a potential risk for aquatic ecosystems in areas adjacent to where the chemical is applied. (C) 2011 Elsevier Inc. All rights reserved.

Time-related effects of general functional training in spinal cord-injured rats

OBJECTIVES: This prospective, randomized, experimental study with rats aimed to investigate the influence of general treatment strategies on the motor recovery of Wistar rats with moderate contusive spinal cord injury. METHODS: A total of 51 Wistar rats were randomized into five groups: control, maze, ramp, runway, and sham (laminectomy only). The rats underwent spinal cord injury at the T9-T10 levels using the NYU-Impactor. Each group was trained for 12 minutes twice a week for two weeks before and five weeks after the spinal cord injury, except for the control group. Functional motor recovery was assessed with the Basso, Beattie, and Bresnahan Scale on the first postoperative day and then once a week for five weeks. The animals were euthanized, and the spinal cords were collected for histological analysis. RESULTS: Ramp and maze groups showed an earlier and greater functional improvement effect than the control and runway groups. However, over time, unexpectedly, all of the groups showed similar effects as the control group, with spontaneous recovery. There were no histological differences in the injured area between the trained and control groups. CONCLUSION: Short-term benefits can be associated with a specific training regime; however, the same training was ineffective at maintaining superior long-term recovery. These results might support new considerations before hospital discharge of patients with spinal cord injuries.

Antihypertensive and antioxidant effects of a single daily dose of sodium nitrite in a model of renovascular hypertension

Dietary nitrite and nitrate have been reported as alternative sources of nitric oxide (NO). In this regard, we reported previously that sodium nitrite added to drinking water was able to exert antihypertensive effects in an experimental model of hypertension in a dose-dependent manner. Taking into consideration that nitrite is continuously converted to nitrate in the bloodstream, here we expanded our previous report and evaluate whether a single daily dose of sodium nitrite could exert antihypertensive effects in 2 kidney-1 clip (2K1C) hypertensive rats. Sham-operated and 2K1C rats were treated with vehicle or sodium nitrite (15 mg/kg/day) for 4 weeks. We evaluated the effects induced by sodium nitrite treatment on systolic blood pressure (SBP) and NO markers such as plasma nitrite, nitrite + nitrate (NOx), cGMP, and blood levels of nitrosyl-hemoglobin. In addition, we also evaluated effects of nitrite on oxidative stress and antioxidant enzymes. Dihydroethidium (DHE) was used to evaluate aortic reactive oxygen species (ROS) production by fluorescence microscopy, and plasma levels of thiobarbituric acid-reactive species (TBARS) were measured in plasma samples from all experimental groups. Red blood cell superoxide dismutase (SOD) and catalase activity were evaluated with commercial kits. Sodium nitrite treatment reduced SBP in 2K1C rats (P < 0.05). We found lower plasma nitrite and NOx levels in 2K1C rats compared with normotensive controls (both P < 0.05). Nitrite treatment restored the lower levels of nitrite and NOx. While no change was found in the blood levels of nitrosyl-hemoglobin (P > 0.05), nitrite treatment increased the plasma levels of cGMP in 2K1C rats (P < 0.05). Higher plasma TBARS levels and aortic ROS levels were found in hypertensive rats compared with controls (P < 0.05), and nitrite blunted these alterations. Lower SOD and catalase activities were found in 2K1C hypertensive rats compared with controls (both P < 0.05). Nitrite treatment restored SOD activity (P < 0.05), whereas catalase was not affected. These data suggest that even a single daily oral dose of sodium nitrite is able to lower SBP and exert antioxidant effects in renovascular hypertension.

Treatment effects of bonded spurs associated with high-pull chincup therapy in the treatment of patients with anterior open bite

Introduction: The aim of this prospective clinical study was to investigate the cephalometric changes produced by bonded spurs associated with high-pull chincup therapy in children with Angle Class I malocclusion and anterior open bite. Methods: Thirty patients with an initial mean age of 8.14 years and a mean anterior open bite of -3.93 mm were treated with bonded spurs associated with chincup therapy for 12 months. An untreated control group of 30 subjects with an initial mean age of 8.36 years and a mean anterior open bite of -3.93 mm and the same malocclusion was followed for 12 months for comparison. Student t tests were used for intergroup comparisons. Results: The treated group demonstrated a significantly greater decrease of the gonial angle, and increase in overbite, palatal tipping of the maxillary incisors, and vertical dentoalveolar development of the maxillary and mandibular incisors compared with the control group. Conclusions: The association of bonded spurs with high-pull chincup therapy was efficient for the correction of the open bite in 86.7% of the patients, with a 5.23-mm (SD, +/- 1.69) overbite increase. (Am J Orthod Dentofacial Orthop 2012;142:487-93)

Urinary glycosaminoglycans in horse osteoarthritis. Effects of chondroitin sulfate and glucosamine

Our objectives were to characterize the urinary excretion of glycosaminoglycans (GAGs) in horse osteoarthritis, and to investigate the effects of chondroitin sulfate (CS) and glucosamine (GlcN) upon the disease. Urinary GAGs were measured in 47 athletic horses, 20 healthy and 27 with osteoarthritis. The effects of CS and GlcN were investigated in mild osteoarthritis. In comparison to normal, urinary GAGs were increased in osteoarthritis, including mild osteoarthritis affecting only one joint. Treatment with CS + GlcN led to a long lasting increase in the urinary CS and keratan sulfate (KS), and significant improvement in flexion test of tarsocrural and metacarpophalangeal joints was observed. In conclusion, urinary CS and KS seems to reflect the turnover rates of cartilage matrix proteoglycans, and the measurement of these compounds could provide objective means of evaluating and monitoring joint diseases. (C) 2011 Elsevier Ltd. All rights reserved.

Effects of a combined aerobic and strength training program in youth patients with acute lymphoblastic leukemia

Cure rates of youth with Acute Lymphoblastic Leukemia (ALL) have increased in the past decades, but survivor's quality of life and physical fitness has become a growing concern. Although previous reports showed that resistance training is feasible and effective, we hypothesized that a more intense exercise program would also be feasible, but more beneficial than low- to moderate-intensity training programs. We aimed to examine the effects of an exercise program combining high-intensity resistance exercises and moderate-intensity aerobic exercises in young patients undergoing treatment for ALL. A quasi-experimental study was conducted. The patients (n = 6; 5-16 years of age) underwent a 12-week intra-hospital training program involving high-intensity strength exercises and aerobic exercise at 70% of the peak oxygen consumption. At baseline and after 12 weeks, we assessed sub-maximal strength (10 repetition-maximum), quality of life and possible adverse effects. A significant improvement was observed in the sub maximal strength for bench press (71%), lat pull down (50%), leg press (73%) and leg extension (64%) as a result of the training (p < 0.01). The parents' evaluations of their children's quality of life revealed an improvement in fatigue and general quality of life, but the children's self-reported quality of life was not changed. No adverse effects occurred. A 12-week in-hospital training program including high-intensity resistance exercises promotes marked strength improvements in patients during the maintenance phase of the treatment for Acute Lymphoblastic Leukemia without side-effects. Parents' evaluations of their children revealed an improvement in the quality of life.

Effect of enzymatic treatment on the cross-flow microfiltration of acai pulp: Analysis of the fouling and recovery of phytochemicals

This study aimed to investigate the effects of pectinase enzyme treatment of acai pulp on cross-flow microfiltration (CFMF) performance and on phytochemical and functional characteristics of their compounds. Analyses of fouling mechanisms were carried out through resistance in series and blocking in law models. The enzymatic treatment was conducted using Ultrazym(R) AFPL (Novozymes A/S) at 500 mg kg(-1) of acai pulp for 30 min at 35 degrees C. Before microfiltrations, untreated and enzyme-treated acai pulps were previously diluted in distilled water (1:3; w/v). CFMFs were conducted using commercial alpha-alumina (alpha-Al2O3) ceramic membranes (Andritz AG, Austria) of 0.2 mu m and 0.8 mu m pore sizes, and 0.0047 m(2) of filtration area. The microfiltration unit was operated in batch mode for 120 min at 25 degrees C and the fluid-dynamic conditions were transmembrane pressure of Delta P = 100 kPa and cross-flow velocity of 3 m s(-1) in turbulent flow. The highest values of permeate flux and accumulated permeate volume were obtained using enzyme-treated pulp and 0.2 mu m pore size membranes with steady flux values exceeding 100 L h(-1) m(-2). For the 0.8 mu m pore size membrane, the estimated total resistance after the microfiltration of enzyme-treated acai pulp was 21% lower than the untreated pulp, and for the 0.2 mu m pore size membrane, it was 18%. Cake filtration was the dominant mechanism in the early stages of most of the CFMF processes. After approximately 20 min, however, intermediate pore blocking and complete pore blocking contributed to the overall fouling mechanisms. The reduction of the antioxidant capacity of the permeates obtained after microfiltration of the enzyme-treated pulp was higher (p < 0.01) than that obtained using untreated pulp. For total polyphenols, on the contrary, the permeates obtained after microfiltration of the enzyme-treated pulp showed a lower mean reduction (p < 0.01) than those from the untreated pulp. The results show that the enzymatic treatment had a positive effect on the CFMF process of acai pulp. (C) 2012 Elsevier Ltd. All rights reserved.