Antipyretic and antioxidant activities of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles in rats

The objective of this study was to determine the effect of eight 5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-carboxyamidepyrazoles (TFDPs) on rat body temperature and baker’s yeast-induced fever. TFDPs or vehicle (5% Tween 80 in 0.9% NaCl, 5 mL/kg) were injected subcutaneously and rectal temperature was measured as a function of time in 28-day-old male Wistar rats (N = 5-12 per group). Antipyretic activity was determined in feverish animals injected with baker’s yeast (Saccharomyces cerevisiae suspension, 0.135 mg/kg, 10 mL/kg, ip). 3-Ethyl- and 3-propyl-TFDP (140 and 200 μmol/kg, respectively, 4 h after yeast injection) attenuated baker’s yeast-induced fever by 61 and 82%, respectively. These two effective antipyretics were selected for subsequent analysis of putative mechanisms of action. We then determined the effects on cyclooxygenase-1 and -2 (COX-1 and COX-2) activities on 1,1-diphenyl-2-picrylhydrazyl (DPPH) oxidation in vitro, on tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels and on leukocyte counts in the washes of peritoneal cavities of rats injected with baker’s yeast. While 3-ethyl- and 3-propyl-TFDP did not reduce baker’s yeast-induced increases of IL-1β or TNF-α levels, 3-ethyl-TFDP caused a 42% reduction in peritoneal leukocyte count. 3-Ethyl- and 3-propyl-TFDP did not alter COX-1 or COX-2 activities in vitro, but presented antioxidant activity in the DPPH assay with an IC50 of 39 mM (25-62) and 163 mM (136-196), respectively. The data indicate that mechanisms of action of these two novel antipyretic pyrazole derivatives do not involve the classic inhibition of the COX pathway or pyrogenic cytokine release.

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.

Correlation between total nitrite/nitrate concentrations and monoamine oxidase (types A and B) and semicarbazide-sensitive amine oxidase enzymatic activities in human mesenteric arteries from non-diabetic and type 2 diabetic patients

The aim of this study was to determine the correlation between total nitrite/nitrate concentrations (NOx) and the kinetic parameters of monoamine oxidase enzymes (MAO-A and MAO-B) and semicarbazide-sensitive amine oxidase (SSAO) in human mesenteric arteries. Arteries were from non-diabetic and type 2 diabetic patients with sigmoid or rectum carcinoma for whom surgery was the first option and who were not exposed to neo-adjuvant therapy. Segments of human inferior mesenteric arteries from non-diabetic (61.1 ± 8.9 years old, 7 males and 5 females, N = 12) and type 2 diabetic patients (65.8 ± 6.2 years old, 8 males and 4 females, N = 12) were used to determine NOx concentrations and the kinetic parameters of MAO-A, MAO-B and SSAO by the Griess reaction and by radiochemical assay, respectively. The NOx concentrations in arteries from diabetic patients did not differ significantly from those of the non-diabetic group (10.28 ± 4.61 vs 10.71 ± 4.32 nmol/mg protein, respectively). In the non-diabetic group, there was a positive correlation between NOx concentrations and MAO-B parameters: Km (r = 0.612, P = 0.034) and Vmax (r = 0.593, P = 0.042), and a negative correlation with the SSAO parameters: Km (r = -0.625, P = 0.029) and Vmax (r = -0.754, P = 0.005). However, in the diabetic group no correlation was found between NOx concentrations and the three kinetic parameters of the enzymes. These results suggest an important function of sympathetic nerves and vascular NOx concentrations in arteries of non-diabetic patients. Thus, these results confirm the importance of a balance between oxidants and antioxidants in the maintenance of vascular homeostasis to prevent oxidative stress.

Study of the comprehension of the scientific method by members of a university health research laboratory

In Brazil, scientific research is carried out mainly at universities, where professors coordinate research projects with the active participation of undergraduate and graduate students. However, there is no formal program for the teaching/learning of the scientific method. The objective of the present study was to evaluate the comprehension of the scientific method by students of health sciences who participate in scientific projects in an academic research laboratory. An observational descriptive cross-sectional study was conducted using Edgar Morin complexity as theoretical reference. In a semi-structured interview, students were asked to solve an abstract logical puzzle - TanGram. The collected data were analyzed using the hermeneutic-dialectic analysis method proposed by Minayo and discussed in terms of the theoretical reference of complexity. The students’ concept of the scientific method is limited to participation in projects, stressing the execution of practical procedures as opposed to scientific thinking. The solving of the TanGram puzzle revealed that the students had difficulties in understanding questions and activities focused on subjects and their processes. Objective answers, even when dealing with personal issues, were also reflected on the students’ opinions about the characteristics of a successful researcher. Students’ difficulties concerning these issues may affect their scientific performance and result in poorly designed experiments. This is a preliminary study that should be extended to other centers of scientific research.

Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32%) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production.

In vitro anti-inflammatory, cytotoxic and antioxidant activities of boesenbergin A, a chalcone isolated from Boesenbergia rotunda (L.) (fingerroot)

The current in vitro study was designed to investigate the anti-inflammatory, cytotoxic and antioxidant activities of boesenbergin A (BA), a chalcone derivative of known structure isolated from Boesenbergia rotunda. Human hepatocellular carcinoma (HepG2), colon adenocarcinoma (HT-29), non-small cell lung cancer (A549), prostate adenocarcinoma (PC3), and normal hepatic cells (WRL-68) were used to evaluate the cytotoxicity of BA using the MTT assay. The antioxidant activity of BA was assessed by the ORAC assay and compared to quercetin as a standard reference antioxidant. ORAC results are reported as the equivalent concentration of Trolox that produces the same level of antioxidant activity as the sample tested at 20 µg/mL. The toxic effect of BA on different cell types, reported as IC50, yielded 20.22 ± 3.15, 10.69 ± 2.64, 20.31 ± 1.34, 94.10 ± 1.19, and 9.324 ± 0.24 µg/mL for A549, PC3, HepG2, HT-29, and WRL-68, respectively. BA displayed considerable antioxidant activity, when the results of ORAC assay were reported as Trolox equivalents. BA (20 µg/mL) and quercetin (5 µg/mL) were equivalent to a Trolox concentration of 11.91 ± 0.23 and 160.32 ± 2.75 µM, respectively. Moreover, the anti-inflammatory activity of BA was significant at 12.5 to 50 µM and without any significant cytotoxicity for the murine macrophage cell line RAW 264.7 at 50 µM. The significant biological activities observed in this study indicated that BA may be one of the agents responsible for the reported biological activities of B. rotunda crude extract.

Sedative and anesthetic activities of the essential oils of Hyptis mutabilis (Rich.) Briq. and their isolated components in silver catfish (Rhamdia quelen)

This study evaluated the sedative and anesthetic effects of the essential oils (EO) of Hyptis mutabilis (Rich.) Briq. and their isolated components on silver catfish (Rhamdia quelen). Quantitative chemical differences between the EOs obtained from leaves and inflorescences were verified, and a new chemotype rich in globulol was described. Although there were no significant differences in the time of induction for sedation and anesthesia between the EOs, only the leaf EO at 344 mg/L anesthetized all fish without side effects. Fractionation of the leaf EO was carried out by column chromatography. The isolated compounds [(+)-1-terpinen-4-ol and (-)-globulol] showed different activity from that detected for the leaf EO in proportional concentrations and similar sedation to a eugenol control at 10 mg/L. However, fish exposed to 1-terpinen-4-ol (3 and 10 mg/L) did not remain sedated for 30 min. Anesthesia was obtained with 83-190 mg/L globulol, but animals showed loss of mucus during induction and mortality at these concentrations. Synergism of the depressor effects was detected with the association of globulol and benzodiazepine (BDZ), compared with either drug alone. Fish exposed to BDZ or globulol+BDZ association showed faster recovery from anesthesia in water containing flumazenil, but the same did not occur with globulol. In conclusion, the use of globulol in aquaculture procedures should be considered only at sedative concentrations of 10 and 20 mg/L, and its mechanism of action seems not to involve the GABAA-BDZ system.

In vitro biological screening of the anticholinesterase and antiproliferative activities of medicinal plants belonging to Annonaceae

The aim of this research was to investigate the antiproliferative and anticholinesterase activities of 11 extracts from 5 Annonaceae species in vitro. Antiproliferative activity was assessed using 10 human cancer cell lines. Thin-layer chromatography and a microplate assay were used to screen the extracts for acetylcholinesterase (AchE) inhibitors using Ellman's reagent. The chemical compositions of the active extracts were investigated using high performance liquid chromatography. Eleven extracts obtained from five Annonaceae plant species were active and were particularly effective against the UA251, NCI-470 lung, HT-29, NCI/ADR, and K-562 cell lines with growth inhibition (GI50) values of 0.04-0.06, 0.02-0.50, 0.01-0.12, 0.10-0.27, and 0.02-0.04 µg/mL, respectively. In addition, the Annona crassiflora and A. coriacea seed extracts were the most active among the tested extracts and the most effective against the tumor cell lines, with GI50 values below 8.90 µg/mL. The A. cacans extract displayed the lowest activity. Based on the microplate assay, the percent AchE inhibition of the extracts ranged from 12 to 52%, and the A. coriacea seed extract resulted in the greatest inhibition (52%). Caffeic acid, sinapic acid, and rutin were present at higher concentrations in the A. crassiflora seed samples. The A. coriacea seeds contained ferulic and sinapic acid. Overall, the results indicated that A. crassiflora and A. coriacea extracts have antiproliferative and anticholinesterase properties, which opens up new possibilities for alternative pharmacotherapy drugs.

Antibacterial and anti-inflammatory activities of an extract, fractions, and compounds isolated from Gochnatia pulchra aerial parts

This paper reports on the in vitro antibacterial and in vivo anti-inflammatory properties of a hydroethanolic extract of the aerial parts of Gochnatia pulchra (HEGP). It also describes the antibacterial activity of HEGP fractions and of the isolated compounds genkwanin, scutellarin, apigenin, and 3,5-O-dicaffeoylquinic acid, as evaluated by a broth microdilution method. While HEGP and its fractions did not provide promising results, the isolated compounds exhibited pronounced antibacterial activity. The most sensitive microorganism was Streptococcus pyogenes, with minimum inhibitory concentration (MIC) values of 100, 50 and 25 µg/mL for genkwanin and the flavonoids apigenin and scutellarin, respectively. Genkwanin produced an MIC value of 25 µg/mL against Enterococcus faecalis. A paw edema model in rats and a pleurisy inflammation model in mice aided investigation of the anti-inflammatory effects of HEGP. This study also evaluated the ability of HEGP to modulate carrageenan-induced interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) production. Orally administered HEGP (250 and 500 mg/kg) inhibited carrageenan-induced paw edema. Regarding carrageenan-induced pleurisy, HEGP at 50, 100, and 250 mg/kg diminished leukocyte migration by 71.43%, 69.24%, and 73.34% (P<0.05), respectively. HEGP suppressed IL-1β and MCP-1 production by 55% and 50% at 50 mg/kg (P<0.05) and 60% and 25% at 100 mg/kg (P<0.05), respectively. HEGP abated TNF-α production by macrophages by 6.6%, 33.3%, and 53.3% at 100, 250, and 500 mg/kg (P<0.05), respectively. HEGP probably exerts anti-inflammatory effects by inhibiting production of the pro-inflammatory cytokines TNF-α, IL-1β, and MCP-1.

Novel retrograde puncture method to establish preperitoneal space for laparoscopic direct inguinal hernia repair with internal ring suturing

The aim of this study was to explore the clinical efficacy of a novel retrograde puncture approach to establish a preperitoneal space for laparoscopic direct inguinal hernia repair with inguinal ring suturing. Forty-two patients who underwent laparoscopic inguinal hernia repair with retrograde puncture for preperitoneal space establishment as well as inguinal ring suturing between August 2013 and March 2014 at our hospital were enrolled. Preperitoneal space was successfully established in all patients, with a mean establishment time of 6 min. Laparoscopic repairs were successful in all patients, with a mean surgical time of 26±15.1 min. Mean postoperative hospitalization duration was 3.0±0.7 days. Two patients suffered from postoperative local hematomas, which were relieved after puncturing and drainage. Four patients had short-term local pain. There were no cases of chronic pain. Patients were followed up for 6 months to 1 year, and no recurrence was observed. Our results demonstrate that preperitoneal space established by the retrograde puncture technique can be successfully used in adult laparoscopic hernioplasty to avoid intraoperative mesh fixation, and thus reduce medical costs.

Show me your brain! Stories of interdisciplinary knowledge creation in practice. Experiences and observations from Aalto Design Factory, Finland.

This dissertation centres on the themes of knowledge creation, interdisciplinarity and knowledge work. My research approaches interdisciplinary knowledge creation (IKC) as practical situated activity. I argue that by approaching IKC from the practice-based perspective makes it possible to “deconstruct” how knowledge creation actually happens, and demystify its strong intellectual, mentalistic and expertise-based connotations. I have rendered the work of the observed knowledge workers into something ordinary, accessible and routinized. Consequently this has made it possible to grasp the pragmatic challenges as well the concrete drivers of such activity. Thus the effective way of organizing such activities becomes a question of organizing and leading effective everyday practices. To achieve that end, I have conducted ethnographic research of one explicitly interdisciplinary space within higher education, Aalto Design Factory in Helsinki, Finland, where I observed how students from different disciplines collaborated in new product development projects. I argue that IKC is a multi-dimensional construct that intertwines a particular way of doing; a way of experiencing; a way of embodied being; and a way of reflecting on the very doing itself. This places emphasis not only the practices themselves, but also on the way the individual experiences the practices, as this directly affects how the individual practices. My findings suggest that in order to effectively organize and execute knowledge creation activities organizations need to better accept and manage the emergent diversity and complexity inherent in such activities. In order to accomplish this, I highlight the importance of understanding and using a variety of (material) objects, the centrality of mundane everyday practices, the acceptance of contradictions and negotiations well as the role of management that is involved and engaged. To succeed in interdisciplinary knowledge creation is to lead not only by example, but also by being very much present in the very everyday practices that make it happen.

Organization of the marketing communication activities after fusion - the integration and the decision making processes

This master’s thesis was made in order to gain answers to the question of how the integration of the marketing communications and the decision making related to it in a geographically dispersed service organization could be improved in a situation where an organization has gone through a merger. The effects of the organizational design dimensions towards the integration of the marketing communications and the decision making related to it was the main focus. A case study as a research strategy offered a perfect frames for an exploratory study and the data collection was conducted by semi-structured interviews and observing. The main finding proved that from the chosen design dimensions, decentralization, coordination and power, could be found specific factors that in a geographically dispersed organization are affecting the integration of the marketing communications negatively. The effects can be seen mostly in the decision making processes, roles and in the division of responsibility, which are affecting the other dimensions and by this, the integration. In a post-merger situation, the coordination dimension and especially the information asymmetry and the information flow seem to have a largest affect towards the integration of the marketing communications. An asymmetric information distribution with the lack of business and marketing education resulted in low self-assurance and at the end in fragmented management and to the inability to set targets and make independent decisions. As conclusions it can be stated, that with the organizational design dimensions can the effects of a merger towards the integration process of the marketing communications to be evaluated.

Finnish doctoral dissertations of nursing education research

Nursing education research has confirmed its place in the discipline of nursing and caring sciences being one of the most central research areas. However, extensive and systematic analysis of nursing education research has been lacking both nationally and internationally. The aim of this study was to describe the focus of nursing education research in Finnish doctoral dissertations in the field of nursing and caring sciences between the years 1990–2014. In addition, the characteristics (i.e. methods, study informants and reporting of validity, reliability, and research ethics) of the dissertations were described. Also, international reviews (N=39) focusing on nursing education research were analysed for a background literature. A literature review was carried out. Altogether 51 (=N) Finnish doctoral dissertations of nursing and caring sciences in the field of nursing education research were included in the final analysis. The data for this research was collected from the open publication lists of each university offering education in nursing and caring sciences in Finland. The dissertations were published in 1990–2014. The data were analysed by content analysis both deductively and inductively. This study consists of a scientific article manuscript and a background literature review. Nursing education research has focused both nationally and internationally on four main areas: structural factors in nursing education, nurse teacherhood, teaching activities, and learning and learning outcomes in nursing education. In Finland, the most central focus area was learning (84.3 %) whereas nurse teacherhood and structural factors in nursing education were studied the least. Students were the predominant study informant group while nurse staff including nurse mentors were next and nurse educators only the third. Surveys and interviews were the most common data collection methods. In the findings there were a lot of similarities with international reviews of nursing education research. Finnish nursing education research has been very student-centred yet studies focusing on the education of other nursing based professions or different levels of education are rare. Future research about nurse teacherhood, curricula and structural factors in nursing education is recommended. There is also a need for experimental designs. In addition, nursing education research should focus on the central phenomena of nursing education and working life. All in all, more nursing education research is needed. Nursing education dissertations cover only 12.3 % of all the dissertations of nursing and caring sciences in Finland.

A Business Incubator, Accelerator, or Coworking Space? Case Health Innovation Village at GE

Health Innovation Village at GE is one of the new communities targeted for startup and growth-oriented companies. It has been established at the premises of a multinational conglomerate that will promote networking and growth of startup companies. The concept combines features from traditional business incubators, accelerators, and coworking spaces. This research compares Health Innovation Village to these concepts regarding its goals, target clients, source of income, organization, facilities, management, and success factors. In addition, a new incubator classification model is introduced. On the other hand, Health Innovation Village is examined from its tenants’ perspective and improvements are suggested. The work was implemented as a qualitative case study by interviewing GE staff with connections to Health Innovation Village as well as startup entrepreneurs and employees’ working there. The most evident features of Health Innovation Village correspond to those of business incubators although it is atypical as a non-profit corporate business incubator. Strong network orientation and connections to venture capitalists are common characteristics of these new types of accelerators. The design of the premises conforms to the principles of coworking spaces, but the services provided to the startup companies are considerably more versatile than the services offered by coworking spaces. The advantages of Health Innovation Village are that there are first-class premises and exceptionally good networking possibilities that other types of incubators or accelerators are not able to offer. A conglomerate can also provide multifaceted special knowledge for young firms. In addition, both GE and the startups gained considerable publicity through their cooperation, indeed a characteristic that benefits both parties. Most of the expectations of the entrepreneurs were exceeded. However, communication and the scope of cooperation remain challenges. Micro companies spend their time developing and marketing their products and acquiring financing. Therefore, communication should be as clear as possible and accessible everywhere. The startups would prefer to cooperate significantly more, but few have the time available to assume the responsibility of leadership. The entrepreneurs also expected to have more possibilities for cooperation with GE. Wider collaboration might be accomplished by curation in the same way as it is used in the well-functioning coworking spaces where curators take care of practicalities and promote cooperation. Communication issues could be alleviated if the community had its own Intranet pages where all information could be concentrated. In particular, a common calendar and a room reservation system could be useful. In addition, it could be beneficial to have a section of the Intranet open for both the GE staff and the startups so that those willing to share their knowledge and those having project offers could use it for advertising.

Gaining a better understanding of how Outward Bound Western Canada course outcomes are achieved : a research study /

This study examined how Outward Bound Western Canada (OBWC) course outcomes are achieved by exploring the relationships among course components, students' characteristics, and course outcomes. OBWC is a wilderness-based adventure education organization that helps students achieve outcomes such as increased self-awareness, self-confidence, motivation, interpersonal skills, concern for others, and concern for the environment. This study explored the ways in which the various components of courses and the characteristics of students contribute to determining the outcomes students experience as a result of their courses. The purpose of the study was to gain a better understanding of how OBWC course outcomes are achieved in order to strengthen adventure education theory, enhance practice at OBWC and other adventure education organizations, and provide a foundation for further research on this topic. As an interpretive case study, this study sought to describe how OBWC course outcomes are achieved and to provide interpretations of the research findings. Data was gathered from OBWC students and instructors using the quantitative and qualitative data collection techniques of questionnaire, interview, and observation. Data collected from 98 participants ensured a considerable breadth to the study, while interviews with a number of participants also enabled the collection of in-depth data. Analysis and triangulation of the data from the various sources allowed discernment of the research findings. A comprehensive and detailed picture of how course outcomes are achieved emerged from the findings. Twenty-nine course components were found to influence course outcomes, including various aspects of course activities, the physical environment, instructors, and the group. The findings indicated that certain course components were most influential in determining increases to students' self-awareness, self-confidence, self-reliance, self-esteem, self-concept, motivation, self-responsibility, interpersonal skills, concern for others, and concern for the environment. A number of course components were found to indirectly contribute to positive course outcomes by helping maximize the effectiveness of other components, by increasing students' motivation while on course, or by facilitating the processing and transference of new information. The findings also suggested that several course components either directly or indirectly affected course outcomes in negative ways. In addition, the gender, age, population, and expectations of students were found to play a role in determining the course outcomes they experienced and in determining which course components caused those outcomes. Interpretation of the findings resulted in the generation of research-based theory. The main theoretical argument derived from the results of the study was that course outcomes are influenced by a combination of course components and characteristics of students. More specifically, the theory generated by the study indicated that five groupings of factors contribute to course outcomes, including course activities, the physical environment, instructors, the group, and students' characteristics. The study was considered in relation to existing adventure education literature and larger theoretical issues. The generated theory and research findings were then used to develop suggestions for improving practice at OBWC and other adventure education organizations, as well as for enhancing future research studies.