First-Line Chemotherapy with Anthracycline and Taxane Combination in Metastatic Breast Cancer. Detection of bone metastases with TRACP 5b

Background: In Finland, breast cancer (BC) is the most common cancer among women, and prostate cancer (PC) that among men. At the metastatic stage both cancers remain essentially incurable. The goals of therapy include palliation of symptoms, improvement or maintenance of quality of life (QoL), delay of disease progression, and prolongation of survival. Balancing between efficacy and toxicity is the major challenge. With increasing costs of new treatments, appropriate use of resources is paramount. When new treatment regimes are introduced into clinical practice a comprehensive assessment of clinical benefit, adverse effects and cost is necessary. Both BC and PC show a predilection to metastasize to bone. Bone metastases cause significant morbidity impairing the patients´ QoL. Diagnosis of bone metastases relies mainly on radiological methods, which however lack optimal sensitivity and specificity. New tools are needed for detection and follow-up of bone metastases. Aims: Anthracyclines and taxanes are effective chemotherapeutic agents in the treatment of metastatic breast cancer (MBC) with different mechanisms of action. Therefore, evaluation of the combination of anthracyclines with taxanes was a justifiable approach in the treatment of MBC patients. We assessed the efficacy, toxicity, cost of treatment and QoL of BC patients treated with first-line chemotherapy for metastatic disease with the combination epirubicin and docetaxel. We also evaluated the diagnostic potential of tartrate-resistant acid phosphatase 5b (TRACP 5b) and carboxyterminal telopeptides of type I collagen (ICTP) in the diagnosis of bone metastases in BC and TRACP 5b in PC patients. Results: The combination of epirubicin and docetaxel was effective in this phase II study, but required individual dose adjustment to avoid neutropenic infections, and the use of growth factors to maintain a feasible dose level. The response rate was 54 % (95 % CI 37-71) and the median overall survival (OS) was 26 months. Of the patients, 87 % were treated for infections. The treatment of adverse events required additional use of health resources mainly due to neutropenic infections, thereby raising direct treatment costs by 20 %. Despite adverse events, the global QoL was not significantly compromised during the treatment. Clinically evident acute cardiac toxicity was not observed. The combination of serum TRACP 5b and ICTP was at least equally sensitive and specific in detection of of bone metastases as commonly used total alkaline phosphatise (tALP) in BC patients. In contrast, TRACP 5b was less specific and sensitive than tALP as a marker of skeletal changes in PC patients. Conclusions: Treatment with epirubicin and docetaxel showed high efficacy in first-line chemotherapy of MBC. The relatively high incidence of neutropenic infections requiring hospitalization increased the treatment costs. Despite adverse events, the global QoL of the patients was not significantly compromised. The combination of TRACP 5b and ICTP showed similar activity as tALP in detecting bone metastases in MBC. In contrast, TRACP 5b was less specific and sensitive than tALP as a marker of skeletal changes in PC.

TOWARDS A PHILOSOPHICAL UNDERSTANDING OF THE LOGICS OF FORMAL INCONSISTENCY

Abstract In this paper we present a philosophical motivation for the logics of formal inconsistency , a family of paraconsistent logics whose distinctive feature is that of having resources for expressing the notion of consistency within the object language in such a way that consistency may be logically independent of non-contradiction. We defend the view according to which logics of formal inconsistency may be interpreted as theories of logical consequence of an epistemological character. We also argue that in order to philosophically justify paraconsistency there is no need to endorse dialetheism, the thesis that there are true contradictions. Furthermore, we show that mbC , a logic of formal inconsistency based on classical logic, may be enhanced in order to express the basic ideas of an intuitive interpretation of contradictions as conflicting evidence.

Use of preclinical and early clinical data for dose selection of a selective estrogen receptor modulator toremifene in treatment of breast cancer

In development of human medicines, it is important to predict early and accurately enough the disease and patient population to be treated as well as the effective and safe dose range of the studied medicine. This is pursued by using preclinical research models, clinical pharmacology and early clinical studies with small sample sizes. When successful, this enables effective development of medicines and reduces unnecessary exposure of healthy subjects and patients to ineffectice or harmfull doses of experimental compounds. Toremifene is a selective estrogen receptor modulator (SERM) used for treatment of breast cancer. Its development was initiated in 1980s when selection of treatment indications and doses were based on research in cell and animal models and on noncomparative clinical studies including small number of patients. Since the early development phase, the treatment indication, the patient population and the dose range were confirmed in large comparative clinical studies in patients. Based on the currently available large and long term clinical study data the aim of this study was to investigate how the early phase studies were able to predict the treatment indication, patient population and the dose range of the SERM. As a conclusion and based on the estrogen receptor mediated mechanism of action early studies were able to predict the treatment indication, target patient population and a dose range to be studied in confirmatory clinical studies. However, comparative clinical studies are needed to optimize dose selection of the SERM in treatment of breast cancer.

New perspectives on the melanocortins and their cardiovascular effects: Potential implications for the treatment of cardiovascular diseases with melanocortin analogues

The melanocortin peptides, including melanocyte-stimulating hormones, α-, β- and γ-MSH, are derived from the precursor peptide proopiomelanocortin and mediate their biological actions via five different melanocortin receptors, named from MC1 to MC5. Melanocortins have been implicated in the central regulation of energy balance and cardiovascular functions, but their local effects, via yet unidentified sites of action, in the vasculature, and their therapeutic potential in major vascular pathologies remain unclear. Therefore, the main aim of this thesis was to characterise the role of melanocortins in circulatory regulation, and to investigate whether targeting of the melanocortin system by pharmacological means could translate into therapeutic benefits in the treatment of cardiovascular diseases such as hypertension. In experiments designed to elucidate the local effects of α-MSH on vascular tone, it was found that α-MSH improved blood vessel relaxation via a nitric oxide (NO)-dependent mechanism without directly contracting or relaxing blood vessels. Furthermore, α-MSH was shown to regulate the expression and function of endothelial NO synthase in cultured human endothelial cells via melanocortin 1 receptors. In keeping with the vascular protective role, pharmacological treatment of mice with α-MSH analogues displayed therapeutic efficacy in conditions associated with vascular dysfunction such as obesity. Furthermore, α-MSH analogues elicited marked diuretic and natriuretic responses, which together with their vascular effects, seemed to provide protection against sodium retention and blood pressure elevation in experimental models of hypertension. In conclusion, the present results identify novel effects for melanocortins in the local control of vascular function, pointing to the potential future use of melanocortin analogues in the treatment of cardiovascular pathologies.

Leishmanicidal and cholinesterase inhibiting activities of phenolic compounds of Dimorphandra gardneriana and Platymiscium floribundum, native plants from Caatinga biome

In recent years, the Brazilian Health Ministry and the World Health Organization have supported research into new technologies that may contribute to the surveillance, new treatments, and control of visceral leishmaniasis within the country. In light of this, the aim of this study was to isolate compounds from plants of the Caatinga biome, and to investigate their toxicity against promastigote and amastigote forms of Leishmania infantum chagasi, the main responsible parasite for South American visceral leishmaniasis, and evaluate their ability to inhibit acetylcholinesterase enzyme (AChE). A screen assay using luciferase-expressing promastigote form and an in situ ELISA assay were used to measure the viability of promastigote and amastigote forms, respectively, after exposure to these substances. The MTT colorimetric assay was performed to determine the toxicity of these compounds in murine monocytic RAW 264.7 cell line. All compounds were tested in vitro for their anti-cholinesterase properties. A coumarin, scoparone, was isolated from Platymiscium floribundum stems, and the flavonoids rutin and quercetin were isolated from Dimorphandra gardneriana beans. These compounds were purified using silica gel column chromatography, eluted with organic solvents in mixtures of increasing polarity, and identified by spectral analysis. In the leishmanicidal assays, the compounds showed dose-dependent efficacy against the extracellular promastigote forms, with an EC50 for scoporone of 21.4µg/mL, quercetin and rutin 26 and 30.3µg/mL, respectively. The flavonoids presented comparable results to the positive control drug, amphotericin B, against the amastigote forms with EC50 for quercetin and rutin of 10.6 and 43.3µg/mL, respectively. All compounds inhibited AChE with inhibition zones varying from 0.8 to 0.6, indicating a possible mechanism of action for leishmacicidal activity.

Five Baltic Ports Togehter: Forecasts, Trends and Recommendations

The ports of Stockholm, Tallinn, Helsinki, Naantali and Turku play key roles in making the Central Baltic region accessible. Effective, competitive, eco-friendly and safe port procedures and solutions for the transportation of goods are of major importance for trade in the Baltic Sea region. This report presents the most essential results and recommendations of the PENTA project, which focused on how ports could better comprehend and face current and future challenges facing carriage of goods by sea. Each of the four work packages (WPs) of the PENTA project analysed the changes from a different perspective. WP2 focused on traffic flows between the PENTA ports. Its main emphasis was on the ports, shipowners, and logistics companies that are the key parties in freight transport and on the changes affecting the economy of those ports. In WP3 noise as an environmental challenge for ports was investigated and the analysis also shed light on the relationship between the port and the city. In WP4 procedures related to safety, security and administrative procedures were researched. The main emphasis was on identifying the requirements for the harmonisation of those procedures. Collaboration is highlighted throughout this report. In order to prepare for the future, it was found that ports need to respond to growing competition, increasing costs and shifts in customer demand by strengthening their existing partnerships with other actors in the maritime cluster. Cargo and passenger transport are the main sources of income for most ports. Cargo traffic between the PENTA ports is expected to grow steadily in the future and the outlook for passenger traffic is positive. However, to prepare for the future, ports should not only secure the core activities which generate revenue but also seek alternative ways to make profit. In order to gain more transit traffic, it is suggested that ports conduct a more thorough study of the future requirements for doing business with Russia. The investigation of noise at ports revealed two specific dilemmas that ports cannot solve alone. Firstly, the noise made by vessels and, secondly, the relationship between the port and the surrounding city. Vessels are the most important single noise source in the PENTA ports and also one of the hardest noise sources to handle. Nevertheless, port authorities in Finland and Sweden are held responsible for all noise in the port area, including noise produced by vessels, which is noise the port authority can only influence indirectly. Building housing by waterfront areas close to ports may also initiate disagreements because inhabitants may want quiet areas, whereas port activities always produce some noise from their traffic. The qualitative aspects of the noise question, cooperating with the stakeholders and the communicating of issues related to noise are just as important. We propose that ports should follow the logic of continuous improvement in their noise management. The administrative barriers discussed in this report are mainly caused by differences in international and national legislation, variations in the customs procedures of each country, the incompatibility of the IT systems used in maritime transport, noncompliance with regulations regarding dangerous goods, and difficulties in applying Schengen regulations to vessels from non-EU countries. Improving the situation is out of the hands of the ports to do alone and requires joint action on a variety of levels, including the EU, national authorities and across administrative borders.

Older Consumers’ Adoption of Online Shopping

The thesis is concerned with the online shopping behavior of older adults, who in this study are at least 60 years old. At the moment, the population is ageing and consumers are buying more and more via the Internet. The objective of the thesis is to understand the large group of older adults in Finland as online customers.The study explores older consumers’ adoption of online shopping with a qualitative research, and it is situated in the research tradition of hermeneutic phenomenology. Phenomenology focuses on the life-world of people. The empirical data was collected by three focus groups with 13 participants altogether. The focus group conversations brought forth that there is not tremendous difference in the motives of older consumers to shop online compared to other age groups. The study strengthened the previous conception of a change toward more ageless market. However, online stores should be designed to accommodate some special needs of older consumers as they occasionally struggle with the logic of websites. Finnish older consumers have adopted online shopping because of perceived convenience and because of tolerable perceived risk during first online shopping experience. Positive experiences strengthen positive attitude toward electronic channel.

Use of herbicides on turfgrass

In crop production, weeds must be controlled so as not to adversely affect crop yield and crop quality. Thus, a low level of weeds infesting a field, in most instances, is not a problem. Except in sod or seed production, turfgrass does not have a yield component. The value of turfgrass is its inherent aesthetic quality and usability. Aesthetic quality is the beauty and value that turfgrass adds to a managed landscape. Usability can be the durability of a sport field, trueness of golf putting green roll, or reduction in soil loss from water runoff or wind. Any weed presence in turfgrass can decrease the aesthetic quality and usability of turfgrass. Utilizing herbicides is the only way to completely control weeds in a turfgrass stand. While it is possible to reduce weed populations using cultural or mechanical management practices, it is impossible to completely eliminate weeds as can be accomplished with herbicides. This manuscript will review the major herbicides used in turfgrass in the United States with respect to their modes of action, herbicide family, and primary use in turfgrass.

Differential susceptibility of biotypes of conyza sumatrensis to Chlorimuron-ethyl herbicide

Horseweed (Conyza spp.) is an annual weed, infesting soybean crops in southern Brazil, with chlorimuron-ethyl being one of the most commonly used herbicides for its control. However, in recent soybean harvests, an unsatisfactory control of this weed using this herbicide was observed, generating suspicion regarding the selection of resistant biotypes. The objective of this study was to evaluate the susceptibility of horseweed biotypes to the herbicide chlorimuron-ethyl. Two experiments were conducted in a greenhouse; in the first one, the biotypes were selected selected, and the second experiment was arranged in a 5 x 5 factorial in a completely randomized design with four replications. The treatments used in the preparation of the dose response curves were doses of the herbicide chlorimuron-ethyl (0.0, 1.56, 3.13, 6.25, 12.5, and 25 g ha-1), applied on the five horseweed biotypes at the 3-4 leaf growth stage. The variables evaluated were visual control percentage and shoot dry weight, compared to the control without herbicide application, and plant acetolactate accumulation. It was concluded that there is a differential susceptibility among the biotypes at doses of less than 20 g ha-1 (dose response curves), which indicates low-level resistance. The practical consequences are the indications of chlorimuron-ethyl application at the maximum doses recomended and that the practice of rotating mechanisms of action must be used in the chemical weed management of these areas.

Helluntailaiset luokkakuvassa. uskontokulttuuri ja yksikön luokka-asema Turun Helluntaiseurakunnassa

Tässä tutkimuksessa analysoin sitä, miten helluntailainen uskontokulttuuri vaikuttaa yksilön valintoihin ja sen kautta siihen, mihin luokka-asemiin seurakuntalaiset ovat päätyneet Turun Helluntaiseurakunnassa. Tutkimus on uskontoantropologinen ja kuuluu uskontotieteen alaan. Siinä yhdistetään sosiologista luokkatutkimusta sekä rationaalisen valinnan ja toiminnan teorioita uskontoantropologisessa viitekehyksessä. Pääasialliseksi aineistoksi keräsin laajan etnografisen aineiston, joka koostuu systemaattisesta havainnoinnista, kyselyistä ja haastatteluista. Lisäksi olen tutkinut seurakunnan ja helluntailaisuutta koskevia arkistoja sekä kirjallisuutta. Tutkimuksen kohde on Turun helluntaiseurakunta, joka muodostaa tutkimusongelman kannalta mielekkään tutkimusasetelman. Tutkimus kertoo olennaista tietoa siitä, miten uskonto vaikuttaa yksilön valintoihin ja hänen yhteiskunnalliseen asemaansa. Tutkimusaineiston pohjalta laadin selittävän mallin kuvaamaan sitä prosessia, miten yksilöt tekevät valintojaan rationaalisina toimijoina eri kulttuurien vaikutuspiireissä. Antropologisena pohjana selitykselle toimii uskonnon rajojen rakentumisen, muuttamisen ja ylittämisen logiikka. Pyhän kategorisoinnin jäsentämä uskontokulttuuri ohjaa yksilöä suosimaan toisia kulttuureja, luokkakulttuureja ja tyylejä sekä vierastamaan toisia. Jos yksilö haluaa tehdä valinnan, joka nähdään arveluttavana, täytyy hänen oikeuttaa se kulttuurinsa sisäisillä symboleilla ja rituaaleilla. Turun Helluntaiseurakunnassa korostuvat auttamisen ja sivistämisen ammatit, kuten lääkäri, sairaanhoitaja ja opettaja. Nämä voidaan edelleen jäljittää seurakunnan opetuksiin sekä seurakuntalaisten käyttämiin diskursseihin ja oletuksiin hyväksytyistä elämäntyyleistä. Lisäksi diskursseissa korostuvat näkemykset ammatista kutsumuksena, koulutuksen itsestäänselvyys sekä asemaan liittyvän radikalismin välttäminen. Seurakunnan uskontokulttuurin keskiluokkaistava vaikutus näkyy ennen kaikkea toisen ja useamman polven helluntailaisissa, jotka sijoittuvat korkeampiin asemiin kuin ulkopuolelta kääntyneet. Seurakunnan uskontokulttuuri vähentää luokkatietoisuuden syntyä ja voi osaltaan ylläpitää yhteiskunnan luokkarakennetta, koska uskonnon ensisijaiset päämäärät eivät kohdistu yhteiskunnan rakenteen muuttamiseen Suomessa. Tutkimuksen mukaan yksilön omat ja häneen kohdistetut oletukset ja arvot, jotka hän kulttuurissa omaksuu, ohjaavat häntä myös kulttuurinsa näkökulmasta suosiollisiin asemiin.

Interactions of ANP and ANG II in tubular nephron acidification

(ANP, 1 µM) on the kinetics of bicarbonate reabsorption in the rat middle proximal tubule, we performed in vivo experiments using a stopped-flow microperfusion technique with the determination of lumen pH by Sb microelectrodes. These studies confirmed that ANG II added to the luminal or peritubular capillary perfusion fluid stimulates proximal bicarbonate reabsorption and showed that ANP alone does not affect this process, but impairs the stimulation caused by ANG II. We also studied the effects and the interaction of these hormones in cortical distal nephron acidification. Bicarbonate reabsorption was evaluated by the acidification kinetic technique in early (ED) and late (LD) distal tubules in rats during in vivo stopped-flow microperfusion experiments. The intratubular pH was measured with a double-barreled microelectrode with H+-sensitive resin. The results indicate that ANG II acted by stimulating Na+/H+ exchange in ED (81%) and LD (54%) segments via activation of AT1 receptors, as well as vacuolar H+-ATPase in LD segments (33%). ANP did not affect bicarbonate reabsorption in either segment and, as opposed to what was seen in the proximal tubule, did not impair the stimulation caused by ANG II. To investigate the mechanism of action of these hormones in more detail, we studied cell pH dependence on ANG II and ANP in MDCK cells using the fluorescent probe BCECF. We showed that the velocity of cell pH recovery was almost abolished in the absence of Na+, indicating that it is dependent on Na+/H+ exchange. ANP (1 µM) alone had no effect on this recovery but reversed both the acceleration of H+ extrusion at low ANG II levels (1 pM and 1 nM), and inhibition of H+ extrusion at higher ANG II levels (100 nM). To obtain more information on the mechanism of interaction of these hormones, we also studied their effects on the regulation of intracellular free calcium concentration, [Ca2+]i, monitored with the fluorescent probe Fura-2 in MDCK cells in suspension. The data indicate that the addition of increasing concentrations of ANG II (1 pM to 1 µM) to the cell suspension led to a progressive increase in [Ca2+]i to 2-3 times the basal level. In contrast, the addition of ANP (1 µM) to the cell suspension led to a very rapid 60% decrease in [Ca2+]i and reduced the increase elicited by ANG II, thus modulating the effect of ANG II on [Ca2+]i. These results may indicate a role of [Ca2+]i in the regulation of the H+ extrusion process mediated by Na+/H+ exchange and stimulated/impaired by ANG II. The data are compatible with stimulation of Na+/H+ exchange by increases of [Ca2+]i in the lower range, and inhibition at high [Ca2+]i levels

Regulation of nephron acidification by corticosteroids

The present paper reviews work from our laboratories evaluating the importance of adrenal cortical hormones in acidification by proximal and cortical distal tubules. Proximal acidification was determined by stationary microperfusion, and measurement of bicarbonate reabsorption using luminal pH determination was performed with H+-ion-sensitive microelectrodes. Rats were adrenalectomized (ADX) 48 h before the experiments, and corticosteroids (aldosterone (A), corticosterone (B), and 18-OH corticosterone (18-OH-B)) were injected intramuscularly 100 and 40 min before the experiments. In ADX rats stationary pH increased significantly to 7.03 as compared to sham-operated rats (6.78). Bicarbonate reabsorption decreased from 2.65 ± 0.18 in sham-operated rats to 0.50 ± 0.07 nmol cm-2 s-1 after ADX. The administration of the three hormones stimulated proximal tubule acidification, reaching, however, only 47.2% of the sham values in aldosterone-treated rats. Distal nephron acidification was studied by measuring urine minus blood pCO2 differences (U-B pCO2) in bicarbonate-loaded rats treated as above. This pCO2 difference is used as a measure of the distal nephron ability to secrete H+ ions into an alkaline urine. U-B pCO2 decreased significantly from 39.9 ± 1.26 to 11.9 ± 1.99 mmHg in ADX rats. When corticosteroids were given to ADX rats before the experiment, U-B pCO2 increased significantly, but reached control levels only when aldosterone (two 3-µg doses per rat) plus corticosterone (220 µg) were given together. In order to control for the effect of aldosterone on distal transepithelial potential difference one group of rats was treated with amiloride, which blocks distal sodium channels. Amiloride-treated rats still showed a significant reduction in U-B pCO2 after ADX. Only corticosterone and 18-OH-B but not aldosterone increased U-B pCO2 back to the levels of sham-operated rats. These results show that corticosteroids stimulate renal tubule acidification both in proximal and distal nephrons and provide some clues about the mechanism of action of these steroids

Effect of angiotensin-(1-7) on reperfusion arrhythmias in isolated rat hearts

There is increasing evidence that angiotensin-(1-7) (Ang-(1-7)) is an endogenous biologically active component of the renin-angiotensin system (RAS). In the present study, we investigated the effects of Ang-(1-7) on reperfusion arrhythmias in isolated rat hearts. Isolated rat hearts were perfused with two different media, i.e., Krebs-Ringer (2.52 mM CaCl2) and low-Ca2+ Krebs-Ringer (1.12 mM CaCl2). In hearts perfused with Krebs-Ringer, Ang-(1-7) produced a concentration-dependent (27-210 nM) reduction in coronary flow (25% reduction at highest concentration), while only slight and variable changes in contraction force and heart rate were observed. Under the same conditions, angiotensin II (Ang II; 27 and 70 nM) produced a significant reduction in coronary flow (39% and 48%, respectively) associated with a significant increase in force. A decrease in heart rate was also observed. In low-Ca2+ Krebs-Ringer solution, perfusion with Ang-(1-7) or Ang II at 27 nM concentration produced similar changes in coronary flow, contraction force and heart rate. In isolated hearts perfused with normal Krebs-Ringer, Ang-(1-7) produced a significant enhancement of reperfusion arrhythmias revealed by an increase in the incidence and duration of ventricular tachycardia and ventricular fibrillation (more than 30-min duration). The facilitation of reperfusion arrhythmias by Ang-(1-7) was associated with an increase in the magnitude of the decreased force usually observed during the post-ischemic period. The effects of Ang-(1-7) were abolished in isolated rat hearts perfused with low-Ca2+ Krebs-Ringer. The effect of Ang II (27 nM) was similar but less pronounced than that of Ang-(1-7) at the same concentration. These results indicate that the heart is a site of action for Ang-(1-7) and suggest that this heptapeptide may be involved in the mediation of the cardiac effects of the RAS

Structural basis for the pathophysiology of lipoprotein(a) in the athero-thrombotic process

Lipoprotein Lp(a) is a major and independent genetic risk factor for atherosclerosis and cardiovascular disease. The essential difference between Lp(a) and low density lipoproteins (LDL) is apolipoprotein apo(a), a glycoprotein structurally similar to plasminogen, the precursor of plasmin, the fibrinolytic enzyme. This structural homology endows Lp(a) with the capacity to bind to fibrin and to membrane proteins of endothelial cells and monocytes, and thereby to inhibit plasminogen binding and plasmin generation. The inhibition of plasmin generation and the accumulation of Lp(a) on the surface of fibrin and cell membranes favor fibrin and cholesterol deposition at sites of vascular injury. Moreover, insufficient activation of TGF-ß due to low plasmin activity may result in migration and proliferation of smooth muscle cells into the vascular intima. These mechanisms may constitute the basis of the athero-thrombogenic mode of action of Lp(a). It is currently accepted that this effect of Lp(a) is linked to its concentration in plasma. An inverse relationship between Lp(a) concentration and apo(a) isoform size, which is under genetic control, has been documented. Recently, it has been shown that inhibition of plasminogen binding to fibrin by apo(a) is also inversely associated with isoform size. Specific point mutations may also affect the lysine-binding function of apo(a). These results support the existence of functional heterogeneity in apolipoprotein(a) isoforms and suggest that the predictive value of Lp(a) as a risk factor for vascular occlusive disease would depend on the relative concentration of the isoform with the highest affinity for fibrin

Effects of acupuncture on behavioral, cardiovascular and hormonal responses in restraint-stressed Wistar rats

Stress is a well-known entity and may be defined as a threat to the homeostasis of a being. In the present study, we evaluated the effects of acupuncture on the physiological responses induced by restraint stress. Acupuncture is an ancient therapeutic technique which is used in the treatment and prevention of diseases. Its proposed mechanisms of action are based on the principle of homeostasis. Adult male Wistar EPM-1 rats were divided into four groups: group I (N = 12), unrestrained rats with cannulas previously implanted into their femoral arteries for blood pressure and heart rate measurements; group II (N = 12), rats that were also cannulated and were submitted to 60-min immobilization; group III (N = 12), same as group II but with acupuncture needles implanted at points SP6, S36, REN17, P6 and DU20 during the immobilization period; group IV (N = 14), same as group III but with needles implanted at points not related to acupuncture (non-acupoints). During the 60-min immobilization period animals were assessed for stress-related behaviors, heart rate, blood pressure and plasma corticosterone, noradrenaline and adrenaline levels. Group III animals showed a significant reduction (60% on average, P<0.02) in restraint-induced behaviors when compared to groups II and IV. Data from cardiovascular and hormonal assessments indicated no differences between group III and group II and IV animals, but tended to be lower (50% reduction on average) in group I animals. We hypothesize that acupuncture at points SP6, S36, REN17, P6 and DU20 has an anxiolytic effect on restraint-induced stress that is not due to a sedative action