Effects of nemorosone, isolated from the plant Clusia rosea, on the cell cycle and gene expression in MCF-7 BUS breast cancer cell lines

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

Cytotoxic and genotoxic effects of high concentrations of the immunosuppressive drugs cyclosporine and tacrolimus in MRC-5 cells

Immunosuppressive drugs are used to suppress immune system activity in transplant patients and reduce the risk of organ rejection. The present study evaluated the potential cytotoxic, genotoxic and mutagenic of the immunosuppressive drugs cyclosporine (CsA) and tacrolimus (FK-506) on normal human fibroblasts (MRC-5 cells). Based on plasma concentrations of the immunosuppressive drugs, which were obtained from the records of kidney transplant patients at the Kidney Institute of Londrina, Brazil, 11 concentrations of each immunosuppressive were chosen to evaluate cell viability using the MIT assay. From these results, CsA and FK-506 concentrations of 135, 300, 675, and 1520 ng/ml and 8, 16, 24, and 32 ng/ml, respectively, were evaluated using (i) the comet assay, (ii) the nuclear division index (NDI), (iii) the micronucleus test (CBMN) and (iv) cell proliferation curves generated by quantifying cell numbers and protein levels. In this study, 1520 to 3420 ng/ml CsA decreased cell viability after 48 h of exposure. Genotoxic effects were observed only with a concentration of 1520 ng/ml after 3 h of exposure and with concentrations of 675 and 1520 ng/ml after 24 h of exposure. Mutagenic effects were observed only for the concentration of 1520 ng/ml. FK-506 decreased cell viability after 72 h of exposure for concentrations up to 20 ng/ml; genotoxic effects were observed with concentrations up to 8 ng/ml for both treatment times (3 and 24 h) and mutagenic effects were observed with concentrations of 24 and 32 ng/ml after 24 h of treatment. The cell proliferation curves demonstrated the absence of cytostatic effects of these drugs, and these data were confirmed by the NDI analysis. Our results suggest that concentrations lower than 300 ng/ml of CsA and 16 ng/ml of FK-506 are safe for use, as they did not induce genotoxic and mutagenic damage or affect MRC-5 cell viability and proliferation. (C) 2014 Elsevier GmbH. All rights reserved.

Effects of late defoliations on chemical and sensory characteristics of cv. Uva Longanesi wines

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

The effects of fiber inclusion on pet food sensory characteristics and palatability

The objectives of this study were to determine (a) the influence of fiber on the sensory characteristics of dry dog foods; (b) differences of coated and uncoated kibbles for aroma and flavor characteristics; (c) palatability of these dry dog foods; and (d) potential associations between palatability and sensory attributes. A total of eight fiber treatments were manufactured: a control (no fiber addition), guava fiber (3%, 6%, and 12%), sugar cane fiber (9%; large and small particle size), and wheat bran fiber (32%; large and small particle size). The results indicated significant effects of fibers on both flavor and texture properties of the samples. Bitter taste and iron and stale aftertaste were examples of flavor attributes that differed with treatment, with highest intensity observed for 12% guava fiber and small particle size sugar cane fiber treatments. Fracturability and initial crispness attributes were lowest for the sugar cane fiber treatments. Flavor of all treatments changed after coating with a palatant, increasing in toasted, brothy, and grainy attributes. The coating also had a masking effect on aroma attributes such as stale, flavor attributes such as iron and bitter taste, and appearance attributes such as porosity. Palatability testing results indicated that the control treatment was preferred over the sugar cane or the wheat bran treatment. The treatment with large sugarcane fiber particles was preferred over the treatment with small particles, while both of the wheat bran treatments were eaten at a similar level. Descriptive sensory analysis data, especially textural attributes, were useful in pinpointing the underlying characteristics and were considered to be reasons that may influence palatability of dog foods manufactured with inclusion of different fibers.

Bupropion treatment increases epididymal contractility and impairs sperm quality with no effects on the epididymal sperm transit time of male rats

Bupropion is a dopamine (DA) and norepinephrine (NE) reuptake inhibitor used as smoking cessation and antidepressant drug with a lower incidence of male sexual dysfunction. We showed previously that sibutramine, a norepinephrine/serotonine reuptake inhibitor, reduced male rat fertility. As there are no studies evaluating the impact of bupropion treatment on spermatic parameters and male fertility, we evaluated the effects of bupropion treatment (15 and 30 mg kg(-1), 30 days) on sexual behavior, spermatic parameters and fertility of male Wistar rats and on the epididymal duct in vitro contractility. Bupropion 15 mg kg(-1) increased the serum luteinizing hormone level and the epididymal duct contractility, but the sperm quality was not affected. At 30 mg kg(-1) bupropion impaired sperm quality increasing the incidence of non-progressive sperm. The male sexual behavior and fertility were not modified at both bupropion doses. These results, in rats, suggest the importance of studies evaluating the effects of bupropion on the human male sperm quality.

Protective effects of the galectin-1 protein on in vivo and in vitro models of ocular inflammation

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

In vivo evaluation of the antimutagenic and antigenotoxic effects of beta-glucan extracted from Saccharomyces cerevisiae in acute treatment with multiple doses

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effects of primovaccination and booster vaccination on serum cortisol and humoral immune response in cattle

The objective of this study was to evaluate the effect of one or two doses of the anti-rabies vaccination on the serum concentration of cortisol and the humoral immune response in cattle as well as the correlation between serum cortisol concentrations and the titers of rabies-neutralizing antibodies. Nelore cattle were randomly assigned to one of three groups, which were vaccinated with one dose of rabies vaccine (group GVSR, N = 15), two doses of rabies vaccine (group GVR, N = 15) or were not vaccinated (group Gc, N = 15). A commercial liquid inactivated rabies vaccine was used. The stressors imposed on the cattle were vaccination, corral handling and the presence of people. Blood samples were collected on days 0, 30 and 60 post-vaccination. Serum cortisol concentrations were determined using a solid-phase radioimmunoassay, and rabies antibody titers were determined using a serum neutralization test with BHK21 cells (RFFIT). Both serum cortisol concentrations and antibody titers increased after the second (booster) vaccination (P < 0.05). In all the groups, the serum cortisol concentrations increased after the cattle were handled in the corral (P < 0.05). No correlation was observed between the serum cortisol concentrations and the antibody titers with any treatment or on any observation day. In conclusion, booster vaccination is indispensable for primovaccinated cattle in achieving high and protective levels of rabies antibodies. Although booster vaccination and frequent cattle handling in corrals are stressors, the response is not strong enough to cause immunosuppression in cattle.

Effects of a synthetic gonadotrophin-releasing hormone agonist, leuprolide, on rut-associated events in male red deer

This study examined the effectiveness of leuprolide, a gonadotrophin-releasing hormone agonist, in suppressing rut-associated events in farmed male red deer. In mid-January (~6 weeks before the rut period in the southern hemisphere) adult red deer (Cervus elaphus scoticus) stags that had been allocated to three groups (n = 10 per group) received leuprolide, administered subcutaneously in a 90-day release formulation, at zero (control), low (22.5 mg) or high (45 mg) doses. Following treatment with leuprolide there was evidence of suppression of mean plasma luteinising hormone concentration that was significant (P < 0.05) at 9 weeks. Mean plasma testosterone concentration of all three groups rose following treatment, then declined prematurely in the low- and high-dose leuprolide-treated groups, so that it was significantly (P < 0.05) suppressed (0.66 ± 0.29 and 2.0 ± 0.88 ng mL–1, low and high dose respectively) in early April when the peak value (9.0 ± 1.94 ng mL–1) was recorded from control stags. A reduction in mean liveweight occurred in all three groups through February–April and this did not differ among treatments. However, a corresponding reduction in mean body condition score was greater in the control stags (P < 0.05). There was little effect of leuprolide treatment on aggressive behaviours, but it lowered roaring frequency in the latter period of the rut. The results indicate that this gonadotrophin-releasing hormone agonist has potential for application in the deer farming industry to suppress undesirable effects of the rut.

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.