Comparison of etoricoxib and indomethacin for the treatment of experimental periodontitis in rats

We investigated the effect of etoricoxib, a selective cyclooxygenase-2 inhibitor, and indomethacin, a non-selective cyclooxygenase inhibitor, on experimental periodontitis, and compared their gastrointestinal side effects. A ligature was placed around the second upper left molars of female Wistar rats (160 to 200 g). Animals (6 per group) were treated daily with oral doses of 3 or 9 mg/kg etoricoxib, 5 mg/kg indomethacin, or 0.2 mL saline, starting 5 days after the induction of periodontitis, when bone resorption was detected, until the sacrifice on the 11th day. The weight and survival rate were monitored. Alveolar bone loss (ABL) was measured as the sum of distances between the cusp tips and the alveolar bone. The gastric mucosa was examined macroscopically and the periodontium and gastric and intestinal mucosa were examined by histopathology. The ongoing ABL was significantly inhibited (P < 0.05) by 3 and 9 mg/kg etoricoxib and by indomethacin: control = 4.08 ± 0.47 mm; etoricoxib (3 mg/kg) = 1.89 ± 0.26 mm; etoricoxib (9 mg/kg) = 1.02 ± 0.14 mm; indomethacin = 0.64 ± 0.15 mm. Histopathology of periodontium showed that etoricoxib and indomethacin reduced inflammatory cell infiltration, ABL, and cementum and collagen fiber destruction. Macroscopic and histopathological analysis of gastric and intestinal mucosa demonstrated that etoricoxib induces less damage than indomethacin. Animals that received indomethacin presented weight loss starting on the 7th day, and higher mortality rate (58.3%) compared to etoricoxib (0%). Treatment with etoricoxib, even starting when ABL is detected, reduces inflammation and cementum and bone resorption, with fewer gastrointestinal side effects.

Effect of Helicobacter pylori infection and acid blockade by lansoprazole on clarithromycin bioavailability

The effect of proton pump inhibitors and Helicobacter pylori infection on the bioavailability of antibiotics is poorly understood. We determined the effects of 5-day oral administration of 60 mg lansoprazole on the bioavailability of clarithromycin in individuals with and without H. pylori infection. Thirteen H. pylori-infected and 10 non-infected healthy volunteers were enrolled in a study with an open-randomized two-period crossover design and a 21-day washout period between phases. Plasma concentrations of clarithromycin in subjects with and without lansoprazole pre-treatment were measured by liquid chromatography coupled to a tandem mass spectrometer. Clarithromycin Cmax and AUC0-10 h were significantly reduced after lansoprazole administration. In addition, lansoprazole treatment of the H. pylori-positive group resulted in a statistically significant greater reduction in Cmax (40 vs 15%) and AUC0-10 h (30 vs 10%) compared to lansoprazole-treated H. pylori-negative subjects. Thus, treatment with lansoprazole for 5 days reduced bioavailability of clarithromycin, irrespective of H. pylori status. This reduction, however, was even more pronounced in H. pylori-infected individuals.

Effects of sodium valproate and carbamazepine on food competition aggression in pigeons

Valproate and carbamazepine (CAR) have been proposed as adjunct alternatives for the control of aggression in psychiatric patients, although no definite conclusions have been reached. We examined the effects of these drugs on food competition offensive aggression and other behaviors in high- and low-aggression food-restricted pigeons. These were divided into pairs containing previously ranked high-aggression (N = 10 pairs) and low-aggression females (N = 10 pairs). In Experiment 1, a pigeon in each pair of high- and low-aggression subjects was treated daily with an oral dose of sodium valproate (50 mg kg-1 mL saline-1) for 15 days. The other animal received the vehicle. On days 1, 7, and 15, food competition trials (10 min) were performed 60 min after treatment. In Experiment 2, one pigeon in each pair was treated daily with an oral dose of CAR (20 mg kg-1 mL saline-1) for 15 days. Each pair was submitted to a food competition trial on days 1, 7, and 15 of treatment. Valproate (15 days of treatment) selectively decreased the time spent in offensive aggression (control: 102.7 ± 9.3 vs valproate: 32.7 ± 9.2 s; P < 0.001, ANOVA-2-TAU) of high-aggression pigeons. This was also the case for 7 and 15 days of CAR treatment (control: 131.5 ± 8.9 vs CAR: 60.4 ± 5.3, P < 0.01, and control: 122.7 ± 7.1 vs CAR: 39.1 ± 5.2; P < 0.001, ANOVA-2-TAU, respectively). Thus, the two anticonvulsive drugs have a similar effect on food competition aggression in pigeons.

Pharmacological study of anti-allergic activity of Syzygium cumini (L.) Skeels

Myrtaceae is a plant family widely used in folk medicine and Syzygium and Eugenia are among the most important genera. We investigated the anti-allergic properties of an aqueous leaf extract of Syzygium cumini (L.) Skeels (SC). HPLC analysis revealed that hydrolyzable tannins and flavonoids are the major components of the extract. Oral administration of SC (25-100 mg/kg) in Swiss mice (20-25 g; N = 7/group) inhibited paw edema induced by compound 48/80 (50% inhibition, 100 mg/kg; P <= 0.05) and, to a lesser extent, the allergic paw edema (23% inhibition, 100 mg/kg; P <= 0.05). SC treatment also inhibited the edema induced by histamine (58% inhibition; P <= 0.05) and 5-HT (52% inhibition; P <= 0.05) but had no effect on platelet-aggregating factor-induced paw edema. SC prevented mast cell degranulation and the consequent histamine release in Wistar rat (180-200 g; N = 7/group) peritoneal mast cells (50% inhibition, 1 µg/mL; P <= 0.05) induced by compound 48/80. Pre-treatment of BALB/c mice (18-20 g; N = 7/group) with 100 mg/kg of the extract significantly inhibited eosinophil accumulation in allergic pleurisy (from 7.662 ± 1.524 to 1.89 ± 0.336 x 10(6)/cavity; P <= 0.001). This effect was related to the inhibition of IL-5 (from 70.9 ± 25.2 to 12.05 ± 7.165 pg/mL) and CCL11/eotaxin levels (from 60.4 ± 8.54 to 32.8 ± 8.4 ng/mL) in pleural lavage fluid, using ELISA. These findings demonstrate an anti-allergic effect of SC, and indicate that its anti-edematogenic effect is due to the inhibition of mast cell degranulation and of histamine and serotonin effects, whereas the inhibition of eosinophil accumulation in the allergic pleurisy model is probably due to an impairment of CCL11/eotaxin and IL-5 production.

Correlation between lactose absorption and the C/T-13910 and G/A-22018 mutations of the lactase-phlorizin hydrolase (LCT) gene in adult-type hypolactasia

The C/T-13910 mutation is the major factor responsible for the persistence of the lactase-phlorizin hydrolase (LCT) gene expression. Mutation G/A-22018 appears to be only in co-segregation with C/T-13910. The objective of the present study was to assess the presence of these two mutations in Brazilian individuals with and without lactose malabsorption diagnosed by the hydrogen breath test (HBT). Ten milk-tolerant and 10 milk-intolerant individuals underwent the HBT after oral ingestion of 50 g lactose (equivalent to 1 L of milk). Analyses for C/T-13910 and G/A-22018 mutations were performed using a PCR-based method. Primers were designed for this study based on the GenBank sequence. The CT/GA, CT/AA, and TT/AA genotypes (lactase persistence) were found in 10 individuals with negative HBT. The CC/GG genotype (lactase non-persistence) was found in 10 individuals, 9 of them with positive HBT results. There was a significant agreement between the presence of mutations in the LCT gene promoter and HBT results (kappa = -0.9, P < 0.001). The CT/AA genotype has not been described previously and seems to be related to lactase persistence. The present study showed a significant agreement between the occurrence of mutations G/A-22018 and C/T-13910 and lactose absorption in Brazilian subjects, suggesting that the molecular test used here could be proposed for the laboratory diagnosis of adult-type primary hypolactasia.

Attenuation of phosphamidon-induced oxidative stress and immune dysfunction in rats treated with N-acetylcysteine

The effect of N-acetylcysteine, a thiolic antioxidant, on attenuation of phosphamidon-induced oxidative stress and immune dysfunction was evaluated in adult male Wistar rats weighing 200-250 g. Rats were divided into four groups, 8 animals/group, and treated with phosphamidon, N-acetylcysteine or the combination of both for 28 days. Oral administration of phosphamidon (1.74 mg/kg), an organophosphate insecticide, increased serum malondialdehyde (3.83 ± 0.18 vs 2.91 ± 0.24 nmol/mL; P < 0.05) and decreased erythrocyte superoxide dismutase (567.8 ± 24.36 vs 749.16 ± 102.61 U/gHb; P < 0.05), catalase activity (1.86 ± 0.18 vs 2.43 ± 0.08 U/gHb; P < 0.05) and whole blood glutathione levels (1.25 ± 0.21 vs 2.28 ± 0.08 mg/gHb; P < 0.05) showing phosphamidon-induced oxidative stress. Phosphamidon exposure markedly suppressed humoral immune response as assessed by antibody titer to ovalbumin (4.71 ± 0.51 vs 8.00 ± 0.12 -log2; P < 0.05), and cell-mediated immune response as assessed by leukocyte migration inhibition (25.24 ± 1.04 vs 70.8 ± 1.09%; P < 0.05) and macrophage migration inhibition (20.38 ± 0.99 vs 67.16 ± 5.30%; P < 0.05) response. Phosphamidon exposure decreased IFN-у levels (40.7 ± 3.21 vs 55.84 ± 3.02 pg/mL; P < 0.05) suggesting a profound effect of phosphamidon on cell-mediated immune response. A phosphamidon-induced increase in TNF-α level (64.19 ± 6.0 vs 23.16 ± 4.0 pg/mL; P < 0.05) suggests a contributory role of immunocytes in oxidative stress. Co-administration of N-acetylcysteine (3.5 mmol/kg, orally) with phosphamidon attenuated the adverse effects of phosphamidon. These findings suggest that oral N-acetylcysteine treatment exerts protective effect and attenuates free radical injury and immune dysfunction caused by subchronic phosphamidon exposure.

Acute electrophysiologic consequences of pyridostigmine inhibition of cholinesterase in humans

The cardiovascular electrophysiologic basis for the action of pyridostigmine, an acetylcholinesterase inhibitor, has not been investigated. The objective of the present study was to determine the cardiac electrophysiologic effects of a single dose of pyridostigmine bromide in an open-label, quasi-experimental protocol. Fifteen patients who had been indicated for diagnostic cardiac electrophysiologic study underwent two studies just before and 90-120 min after the oral administration of pyridostigmine (45 mg). Pyridostigmine was well tolerated by all patients. Wenckebach nodal anterograde atrioventricular point and basic cycle were not altered by pyridostigmine. Sinus recovery time (ms) was shorter during a 500-ms cycle stimulation (pre: 326 ± 45 vs post: 235 ± 47; P = 0.003) but not during 400-ms (pre: 275 ± 28 vs post: 248 ± 32; P = 0.490) or 600-ms (pre: 252 ± 42 vs post: 179 ± 26; P = 0.080) cycle stimulation. Pyridostigmine increased the ventricular refractory period (ms) during the 400-ms cycle stimulation (pre: 238 ± 7 vs post: 245 ± 9; P = 0.028) but not during the 500-ms (pre: 248 ± 7 vs post: 253 ± 9; P = 0.150) or 600-ms (pre: 254 ± 8 vs post: 259 ± 8; P = 0.255) cycle stimulation. We conclude that pyridostigmine did not produce conduction disturbances and, indeed, increased the ventricular refractory period at higher heart rates. While the effect explains previous results showing the anti-arrhythmic action of pyridostigmine, the clinical impact on long-term outcomes requires further investigation.

Effect of escitalopram on the processing of emotional faces

Serotonin has been implicated in the neurobiology of depressive and anxiety disorders, but little is known about its role in the modulation of basic emotional processing. The aim of this study was to determine the effect of the selective serotonin reuptake inhibitor, escitalopram, on the perception of facial emotional expressions. Twelve healthy male volunteers completed two experimental sessions each, in a randomized, balanced order, double-blind design. A single oral dose of escitalopram (10 mg) or placebo was administered 3 h before the task. Participants were presented to a task composed of six basic emotions (anger, disgust, fear, happiness, sadness, and surprise) that were morphed between neutral and each standard emotion in 10% steps. Escitalopram facilitated the recognition of sadness and inhibited the recognition of happiness in male, but not female faces. No drug effect on subjective measures was detected. These results confirm that serotonin modulates the recognition of emotional faces, and suggest that the gender of the face can have a role in this modulation. Further studies including female volunteers are needed.

Effects of isoflavone on the learning and memory of women in menopause: a double-blind placebo-controlled study

Hormone decline is common to all women during aging and, associated with other factors, leads to cognitive impairment. Its replacement enhances cognitive performance, but not all women present a clinical and family or personal history that justifies its use, mainly women with a history of cancer. The aim of this study was to determine whether a daily oral dose of 80 mg of isoflavone extract for 4 months can produce benefits in women with low hormone levels, contributing to improvement in cognitive aspects. The sample comprised 50- to 65-year-old women whose menstruation had ceased at least 1 year before and who had not undergone hormone replacement. The volunteers were allocated to two groups of 19 individuals each, i.e., isoflavone and placebo. There was a weak correlation between menopause duration and low performance in the capacity to manipulate information (central executive). We observed an increase in the capacity to integrate information in the group treated with isoflavone, but no improvement in the capacity to form new memories. We did not observe differences between groups in terms of signs and symptoms suggestive of depression according to the Geriatric Depression Scale. Our results point to a possible beneficial effect of isoflavone on some abilities of the central executive. These effects could also contribute to minimizing the impact of memory impairment. Further research based on controlled clinical trials is necessary to reach consistent conclusions.

In vivo and in vitro anti-inflammatory and anti-nociceptive activities of lovastatin in rodents

Statins are among the most prescribed drugs in recent clinical practice. They are also known for their pleiotropic actions, which are independent of their lipid-lowering properties. The effect of lovastatin was investigated against carrageenan-induced paw edema in male Wistar rats (200-250 g) and on leukocyte migration, as measured by carrageenan-induced peritonitis in male Swiss mice (20-25 g), which are models of acute inflammation. Lovastatin (administered 1 h prior to carrageenan), at oral doses of 2, 5, and 10 mg/kg, markedly attenuated paw edema formation in rats at the 4th hour after carrageenan injection (25, 43, and 37% inhibition, respectively). Inhibitions of 20, 45 and 80% were observed in the leukocyte migration, as evaluated by carrageenan-induced peritonitis in mice with lovastatin doses of 0.5, 1 and 5 mg/kg, as compared to controls. Furthermore, lovastatin (administered 1 h before initiation) reduced the nociceptive effect of the formalin test in mice, at both phases, at doses of 2, 5, and 10 mg/kg: first phase (51, 65, and 70%, respectively) and second phase (73, 57, and 66% inhibition of licking time, respectively). The anti-nociceptive activity of lovastatin was inhibited by naloxone (3 mg/kg, sc). Lovastatin (0.01, 0.1, and 1 µg/mL) inhibited by 23, 79, and 86%, respectively, the release of myeloperoxidase from human neutrophils. Leukocyte (predominantly neutrophils) infiltration was almost completely reduced by lovastatin treatment, as observed in the model of acute paw edema with hematoxylin and eosin staining. In addition, lovastatin decreased the number of cells expressing tumor necrosis factor-α (TNF-α) and the inducible form of nitric oxide synthase (iNOS) activity. Therefore, the alterations in leukocyte activity and cytokine release could contribute to the anti-inflammatory activity of lovastatin.

Trilling race : the political economy of racialised visual-aural encounters

This thesis investigates the matter of race in the context of Finnish language acquisition among adult migrants in Finland. Here matter denotes both the materiality of race and how race comes to matter. Drawing primarily on an auto/ethno/graphic account of learning the Finnish language as a participant in the Finnish for foreigners classes, this thesis problematises the ontology and epistemology of race, i.e., what race is, how it is known, and what an engagement with race entails. Taking cues from the bodily practices of learning the Finnish trill or the rolling r, this study proposes a notion of “trilling race” and argues for an onto-epistemological dis/continuity that marks race’s arrival. The notion of dis/continuity reworks the distinction between continuity and discontinuity, and asks about the how of the arrival of any identity, the where, and the when. In so doing, an analysis of “trilling race” engages with one of the major problematics that has exercised much critical attention, namely: how to read race differently. That is, to rethink the conundrum of the need to counter “representational weight” (Puar 2007, 191) of race on the one hand, and to account for the racialised lived realities on the other. The link between a study of the phenomenon of host country language acquisition and an examination of the question of race is not as obvious as it might seem. For example, what does the argument that the process of language learning is racialised actually imply? Does it mean that race, as a process of racialisation or an ongoing configuration of sets of power relations, exerts force from an outside on the otherwise neutral process of learning the host country language? Or does it mean that race, as an identity category, presents as among the analytical perspectives, along with gender and class for instance, of the phenomenon of host country language acquisition? With these questions in mind, and to foreground the examination of the question of race in the context of Finnish language acquisition among adult migrants, this thesis opens with a discussion of the art installation Finnexia by Lisa Erdman. Finnexia is a fictitious drug said to facilitate Finnish language learning through accelerating the cognitive learning process and reducing the anxiety of speaking the Finnish language. Not only does the Finnexia installation make visible the ways in which the lack of skill in Finnish is fgured as the threshold – a border that separates the inside from the outside – to integration, but also, and importantly, it raises questions about the nature of difference, and the process of differentiation that separates the individual from the social, fact from fiction, nature from culture. These puzzles animate much of the analysis in this dissertation. These concerns continue to be addressed in the rest of part one. Whereas chapter two offers a reconsideration of the ambiguities of ethnisme/ethnicity and race, chapter three dilates on the methodological implications of a conception of the dis/continuity of race. Part two focuses on the matter of race and examines the political economy of visual-aural encounters, whereas part three shifts the focus and rethinks the possibilities and limitations of transforming racialised and normative constraints. Taking up these particular problematics, this thesis as a whole argues that race trills itself: its identity/difference is simultaneously made possible and impossible.

Probiotics and oral health: In vitro and clinical studies

Aino Toiviainen Probiotics and oral health: in vitro and clinical studies University of Turku, Faculty of Medicine, Institute of Dentistry, Periodontology, Finnish Doctoral Program in Oral Sciences (FINDOS-Turku), Turku, Finland Annales Universitatis Turkuensis, Sarja – Ser. D, Medica-Odontologica. Painosalama Oy, Turku, Finland, 2015 Probiotics are used, for example, to prevent and treat diarrhea, allergies and respiratory infections, and there is an increasing interest to use probiotics also for oral health purposes. The most commonly used probiotic bacteria are lactobacilli and bifidobacteria, which are acidogenic and aciduric. From the oral point of view, use of these probiotics may, at least in theory, mean an increased risk of caries. In this thesis, the effects of probiotics on oral microbial composition, acid production of dental plaque and gingival health were studied through in vitro studies and two clinical studies. In a randomized, double-blind and crossover study, 13 healthy adults were allocated into two groups. Half of the subjects first consumed Lactobacillus rhamnosus GG tablets twice a day for two weeks, and after the washout period, L. reuteri tablets twice a day for two weeks. The other half of the subjects used the tablets in reverse order. In another controlled, randomized and double-blind study, 62 healthy adults were allocated into two groups. One group used the test tablets containing L. rhamnosus GG and B. lactis BB-12 and the other group used control tablets without probiotics. The recommendation for the use of the tablets was 4 per day for 4 weeks. Probiotic lactobacilli interfered with S. mutans biofilm formation and the adhesion of S. mutans to saliva-coated hydroxyapatite in vitro. No effect was found in S. mutans levels in the three-species biofilms. In clinical studies, the studied probiotics had no effect on the acid production of plaque. The counts of mutans streptococci and the oral microbial composition remained the same. Tablets containing L. rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12 did decrease the amount of plaque and gingival bleeding. According to our results, it seems that probiotics have beneficial effects on gingival health. The present results confirmed that probiotics are safe and have beneficial effects on oral health. Since the consumption of probiotics by the general population is steadily increasing, an understanding of the functions of probiotics in the oral cavity has become more important. Keywords: lactobacilli, bifidobacteria, caries, periodontal disease, mutans streptococci, probiotics

Effect of extracts from araticum (Annona crassiflora) on CCl4-induced liver damage in rats

The influence of ethanolic extracts of Annona crassiflora on the activities of hepatic antioxidant enzymes was examined. Extracts of A. crassiflora seeds and peel were administered orally (50 mg of galic acid equivalents.kg-1) to Wistar rats for 14 consecutive days followed by a single oral dose of carbon tetrachloride (CCl4, 2 g.kg-1). Lipid peroxidation and the activities of hepatic catalase (CAT), cytochromes P450 (CP450) and b5, glutathione peroxidase (GPx), glutathione reductase (GRed), superoxide dismutase (SOD), and the content of glutathione equivalents (GSH) were evaluated. The treatment with CCl4 increased lipid peroxidation, the level of GSH equivalents and the content of cytochrome b5 by 44, 140 and 32%, respectively, with concomitant reductions of 23, 34 and 39% in the activities of CAT, SOD, and CP450, respectively. The treatment with A. crassiflora seeds and peel extracts alone inhibited lipid peroxidation by 27 and 22%, respectively without affecting the CP450 content. The pretreatment with the A. crassiflora extracts prevented the lipid peroxidation, the increase in GSH equivalents and the decrease in CAT activity caused by CCl4, but it had no effect on the CCl4-mediated changes in CP450 and b5 and SOD. These results show that A. crassiflora seeds and peel contain antioxidant activity in vivo that could be of potential therapeutic use.

Sustainable sourcing in global supply network: assessment of geographic challenges and management methods Case: Stora Enso

The purpose of this work was to describe and compare sourcing practices and challenges in different geographies, to discuss possible options to advance sustainability of global sourcing, and to provide examples to answer why sourcing driven by sustainability principles is so challenging to implement. The focus was on comparison between Europe & Asia & South-America from the perspective of sustainability adoption. By analyzing sourcing practices of the case company it was possible to describe main differences and challenges of each continent, available sourcing options, supplier relationships and ways to foster positive chance. In this qualitative case study gathered theoretical material was compared to extensive sourcing practices of case company in a vast supplier network. Sourcing specialist were interviewed and information provided by them analyzed in order to see how different research results and theories are reflecting reality and to find answers to proposed research questions.

Risk management in transportation companies: Russian and Finnish practices

Development of risk management practices became significant part of transportation companies’ strategy. Evolution from insurance management into enterprise risk management (ERM) led to development of risk management tools and methods. The purpose of this thesis is to design technique for evaluation of risk management practices of national transportation companies. The empirical research is made on the example of Russian and Finnish transportation companies. The required data was conducted with a help of survey. The result of the thesis is designed technique for risk management practices evaluation that allows to compare practices of different countries and organizations with different characteristics. The Master thesis has novelty in theoretical and practical contribution. It was designed new technique based on realization of the method of APIS. Moreover, it has practical implication as managers can utilize this method for comparison of practices between different countries, different organization and even different units within particular organization.