Efeitos alelopáticos de extratos aquosos de Crinum americanum L.

Investigamos a ação de extratos aquosos de Crinum americanum L. sobre a germinação e crescimento inicial de Lactuca sativa L., Sesamum indicum L. e Raphanus sativus L. e das espécies invasoras: Echinochloa crusgalli (L.) P. Beauv., Ipomoea grandifolia (Dammer) O'Donell e Bidens pilosa L. Preparamos os extratos aquosos a partir de exemplares de um estuário cego em Caraguatatuba, São Paulo. Montamos controles osmóticos com PEG 6000. Analisamos os dados de germinação com Kruskal-Wallis e pós-teste de Dunn, e os dados de crescimento inicial com ANOVA e pós-teste de Tukey. Para todas as espécies testadas obtivemos diminuição na porcentagem e no crescimento inicial e aumento do tempo médio da germinação. O controle osmótico indicou pouca influência da osmolaridade na germinação. Concluímos que C. americanum possui potencial alelopático sobre as espécies testadas.

Anaesthesia and Pain Management for Use in Orthopaedic Day Surgery

Day surgery has gained a large popularity during the last decades. In Finland, 57% of the elective procedures, and 50% at Turku University Hospital, were already conducted on day basis during 2012. The steady growth of day surgery is mostly due to an increased safety in perioperative care and cost-effectiveness. The development of surgical techniques and anaesthetic methods has advanced the modern day surgery and extended the repertory of the procedures for use in day surgery operations. Day surgery also offers certain benefits like reduced risk for hospital-related infections, stress and confusion. Patient satisfaction, regarding several issues, is high. Most concerns and complaints are related to postoperative pain, nausea and vomiting pain and nausea. Pain can hamper recovery and pain management is a crucial factor for hospital discharge. Appropriate pain treatment is effective, safe, easy and economical. A procedure-specific approach and an individually planned, multimodal analgesia should be the basis of modern pain management. The main aim of this thesis was to evaluate the effectiveness and safety of anaesthetic technique and methods in pain treatment of orthopaedic day case surgery, and following conclusions were made. Unilateral spinal block was achieved using hyperbaric bupivacaine with a small dose of clonidine but clonidine prolonged the block. Continuous subacromial bupivacaine was found to be safe but conferring only moderate efficacy in pain care after shoulder arthroscopy. Transdermal fentanyl, 12 g/h, as part of multimodal analgesia, offered a safe and easy option to pain management in this patient group. However, after forefoot surgery, it did not reduce pain any further. In general, pain scores in all patient groups were low and the need for rescue opioid moderate.

The effect of water stress on seed germination of three terrestrial bromeliads from restinga

Bromeliad seedlings are rarely found on sandy coastal plains (restinga), limited, probably, by stressful conditions and/or specific abiotic requirements for germination. The effect of water stress on rate, time, synchronicity and spreading of germination was evaluated here for three terrestrial bromeliads from the restinga of Maricá using osmotic solutions of polyethyleneglicol 6000 (PEG 6000), from 0.0 to -0.26 MPa for 30 days. Water stress induced by PEG lowered rate and increased time and synchronicity values, besides the number of daily events of bromeliad seed germination, under water potentials between 0.00 to -0.14 MPa. No seeds germinated under water potentials lower than -0.14 MPa. These results reinforce a constant and/or high moisture requirement for bromeliad seeds to germinate. We conclude that bromeliads are not able to act as pioneer plants through germination outside the vegetation islands of the restinga of Maricá, due to the inability of seeds to germinate under lower water potential.

Liiketoimintatiedonhallinnan hyödyntämisen esteet päätettäessä palveluista. Case: Kunnalliset pelastustoimen liikelaitokset ja eriytetyt taseyksiköt

Pelastuslaitosten liiketoimintatiedonhallinnalla, tietoperusteisuudella ja tietojohtamisella on tulevaisuudessa merkittävä rooli päätettäessä palveluista. Julkisen pelastustoimen kuntien liikelaitoksina ja eriytettyinä taseyksiköinä toimivien pelastuslaitosten haasteet tulevat olemaan jatkossa tehokkaiden ja vaikuttavien palveluiden strategisessa johtamisessa ja suunnittelussa. Näistä asioista päättäminen on kriittinen vaihe onnistumisen kannalta. Päätöksenteko eri tasoilla tarvitsee tuekseen toiminnasta ja palveluista kanavoitua analysoitua tietoa. Asiakastarpeesta lähtevä vaikuttavuus ja laatu korostuvat. Liiketoimintatiedonhallinta ja tietoperusteisuus haastavat pelastuslaitoksen johtamisjärjestelmän. Johtamisen kyvykkyys ja henkilöstön osaaminen ovat tietoperusteisuuden ja tiedonhallinnan keskiössä. Systemaattisen liiketoimintatiedonhallinnan ja tietoperusteisuuden erottaa perinteisestä virkamiehen tietojen hyväksikäytöstä käsitteen kokonaisvaltaisuus ja järjestelmällisyys kaikessa tiedollisessa toiminnassa. Tämä kattaa tietojärjestelmät, mittarit, prosessit, strategian suunnitelmat, asiakirjat, raportoinnin, kehittämisen ja tutkimuksen. Liiketoimin-tatiedonhallinta ja tietojohtaminen linkittävät kaiken toisiinsa muodostaen keskinäisriippuvaisen yhtenäisen järjestelmän ja kokonaisvaltaisen ymmärryksen. Tutkimukseni on laadullinen tutkimus jossa tiedon keruu ja analysointi on toteutettu toisiaan tukevilla tutkimusotteilla. Metodologia nojaa teorialähtöiseen systemaattiseen analyysiin, jossa on valikoituja osia sisällön analyysistä. Tutkimuksessa on käytetty aineisto- ja menetelmätriangulaatioita. Tutkimuksen aineisto on kerätty teemahaastatteluilla valittujen kohde pelastuslaitosten asiantuntijoilta palveluiden päätös- ja suunnittelutasolta, johtoryhmistä ja joh-tokunnista. Haastatteluja varten tutkija on tutustunut kohdepelastuslaitosten palveluita mää-rittävään tiedolliseen dokumentaatioon kuten palvelutasopäätöksiin ja riskianalyyseihin. Ai-neisto keruun kohteiksi valikoitui pääkaupunkiseudun alueen pelastuslaitokset: Helsingin kaupungin pelastuslaitos sekä Itä-, Keski- ja Länsi-Uudenmaan pelastuslaitokset. Tulosten mukaan pelastuslaitosten keskeiset liiketoimintatiedonhallinnan esteet muodostuvat johtamisen ongelmista, organisaation muutosvastarinnasta ja päätöksenteon tietoperusteen puutteesta. Nämä ilmenevät strategisen johtamisen puutteina, vaikuttavuuden mittaamisen sekä tiedon jalostamisen ongelmina. Keskeistä tiedollista yhdistävää ja linkittävää tekijää ei tunnisteta ja löydetä. Tiedollisessa liiketoimintatiedonhallinnan prosessityössä voisi olla tulos-ten mukaan mahdollisuuksia tämän tyhjiön täyttämiseen. Pelastuslaitoksille jää tulevaisuudessa valinta suunnasta johon ne haluavat edetä tiedonhal-linnan, tietojohtamisen ja tietoperusteisuuden kanssa. Tämä vaikuttaa kehitykseen ja tavoitteeseen keskeisistä palveluiden päätöksentekoa tukevista johtamis- ja tietojärjestelmistä, tietoa kokoavista ja luovista dokumenteista sekä organisaation joustavasta rakenteesta. Tietoprosessiin, tiedon prosessimaiseen johtamiseen ja systemaattiseen tiedonhallintaan meneminen vaikuttaa tutkimuksen tulosten mukaan lupaavalta mahdollisuudelta. Samalla se haastaa pelauslaitokset suureen kulttuuriseen muutokseen ja asettaa uusien vaikuttavuusmittareiden tuottaman tiedon ennakoivan hyväksynnän vaateen strategiselle suunnittelulle. Tämä vaatii pelastuslaitosten johdolta ja henkilöstöltä osaamista, yhteisymmärrystä, muutostarpeiden hyväksyntää sekä asiakkaan asettamista vaikuttavuuden keskiöön.

Influência do déficit hídrico na germinação de sementes e no desenvolvimento inicial de três espécies de Pleurothallidinae (Orchidaceae)

A subtribo Pleurothallidinae possui cerca de 4.100 espécies em 36 gêneros, e ocorre somente nas Américas. Acianthera teres (Lindl.) Borba é rupícola e exposta a luz e a altas temperaturas. Octomeria gracilis Lood. ex Lindl. e Octomeria crassifolia Lindl. são epífitas de florestas, porém, a primeira ocorre em áreas úmidas e a segunda em locais mais secos. A disponibilidade de água influencia o metabolismo nas diversas etapas do desenvolvimento vegetal. Objetivou-se com este trabalho avaliar a influência do déficit hídrico, induzido pela adição de polietileno glicol 6000 (PEG) ao meio de cultura, na germinação e desenvolvimento inicial em A. teres, O. crassifolia e O. gracilis. A semeadura foi efetuada em meio MS/2, sob quatro tratamentos: controle (sem adição de PEG), e com 50 g L-1, 100 g L-1 e 200 g L-1 de PEG, induzindo potenciais hídricos de -0,53, -0,70, -0,86 e -1,60 MPa, respectivamente. Foram realizadas análises aos 45, 120 e 180 dias de cultivo. Em A. teres, observou se que o menor potencial hídrico do meio resulta em menor taxa de germinação e maior retardo do desenvolvimento inicial das plantas. Em O. crassifolia, quanto menor o potencial hídrico do meio, maior a taxa de germinação, contudo, o desenvolvimento foi semelhante entre os tratamentos aos 180 dias. Octomeria gracilis possui certa tolerância a redução do potencial hídrico até 120 dias, e desenvolvimento mais rápido em potenciais hídricos de -0,53 e -0,70 MPa.

New strategies in hematopoietic stem cell transplantation: G-CSF-mobilized unprocessed whole blood

Transplantation of mobilized peripheral blood stem cells (PBSC) for rescue of bone marrow function after high-dose chemo-/radiotherapy is widely used in hematologic malignancies and solid tumors. Mobilization of stem cells to the peripheral blood can be achieved by cytokine treatment of the patients. The main advantage of autologous PBSC transplantation over bone marrow transplantation is the faster recovery of neutrophil and platelet counts. The threshold number of PBSC required for adequate rescue of bone marrow is thought to be about 2 x 106 CD34+ cells/kg, if the stem cells are collected by leukapheresis and subsequently cryopreserved. We show that this critical number could be further reduced to as few as 0.2 x 106 cells/kg. In 30 patients with multiple myeloma and 25 patients with bad risk lymphoma 1 liter of granulocyte colony-stimulating factor (G-CSF)-mobilized unprocessed whole blood (stored at 4oC for 1-3 days) was used for transplantation. Compared to a historical control group, a significant reduction in the duration of neutropenia, thrombocytopenia and the length of hospital stay was documented. Furthermore, the effect of stem cell support was reflected by a lower need for platelet and red cell transfusions and a reduced antibiotic use. Considering the data as a whole, a cost saving of about 50% was achieved. To date, this easy to perform method of transplantation is only feasible following high-dose therapies that are completed within 72 h, since longer storage of unprocessed blood is accompanied by a substantial loss of progenitor cell function. Ongoing investigations include attempts to prolong storage times for whole blood

Linguistic models for decision support

Linguistic modelling is a rather new branch of mathematics that is still undergoing rapid development. It is closely related to fuzzy set theory and fuzzy logic, but knowledge and experience from other fields of mathematics, as well as other fields of science including linguistics and behavioral sciences, is also necessary to build appropriate mathematical models. This topic has received considerable attention as it provides tools for mathematical representation of the most common means of human communication - natural language. Adding a natural language level to mathematical models can provide an interface between the mathematical representation of the modelled system and the user of the model - one that is sufficiently easy to use and understand, but yet conveys all the information necessary to avoid misinterpretations. It is, however, not a trivial task and the link between the linguistic and computational level of such models has to be established and maintained properly during the whole modelling process. In this thesis, we focus on the relationship between the linguistic and the mathematical level of decision support models. We discuss several important issues concerning the mathematical representation of meaning of linguistic expressions, their transformation into the language of mathematics and the retranslation of mathematical outputs back into natural language. In the first part of the thesis, our view of the linguistic modelling for decision support is presented and the main guidelines for building linguistic models for real-life decision support that are the basis of our modeling methodology are outlined. From the theoretical point of view, the issues of representation of meaning of linguistic terms, computations with these representations and the retranslation process back into the linguistic level (linguistic approximation) are studied in this part of the thesis. We focus on the reasonability of operations with the meanings of linguistic terms, the correspondence of the linguistic and mathematical level of the models and on proper presentation of appropriate outputs. We also discuss several issues concerning the ethical aspects of decision support - particularly the loss of meaning due to the transformation of mathematical outputs into natural language and the issue or responsibility for the final decisions. In the second part several case studies of real-life problems are presented. These provide background and necessary context and motivation for the mathematical results and models presented in this part. A linguistic decision support model for disaster management is presented here – formulated as a fuzzy linear programming problem and a heuristic solution to it is proposed. Uncertainty of outputs, expert knowledge concerning disaster response practice and the necessity of obtaining outputs that are easy to interpret (and available in very short time) are reflected in the design of the model. Saaty’s analytic hierarchy process (AHP) is considered in two case studies - first in the context of the evaluation of works of art, where a weak consistency condition is introduced and an adaptation of AHP for large matrices of preference intensities is presented. The second AHP case-study deals with the fuzzified version of AHP and its use for evaluation purposes – particularly the integration of peer-review into the evaluation of R&D outputs is considered. In the context of HR management, we present a fuzzy rule based evaluation model (academic faculty evaluation is considered) constructed to provide outputs that do not require linguistic approximation and are easily transformed into graphical information. This is achieved by designing a specific form of fuzzy inference. Finally the last case study is from the area of humanities - psychological diagnostics is considered and a linguistic fuzzy model for the interpretation of outputs of multidimensional questionnaires is suggested. The issue of the quality of data in mathematical classification models is also studied here. A modification of the receiver operating characteristics (ROC) method is presented to reflect variable quality of data instances in the validation set during classifier performance assessment. Twelve publications on which the author participated are appended as a third part of this thesis. These summarize the mathematical results and provide a closer insight into the issues of the practicalapplications that are considered in the second part of the thesis.

Pancreatic nitric oxide and oxygen free radicals in the early stages of streptozotocin-induced diabetes mellitus in the rat

The objective of the present study was to explore the regulatory mechanisms of free radicals during streptozotocin (STZ)-induced pancreatic damage, which may involve nitric oxide (NO) production as a modulator of cellular oxidative stress. Removal of oxygen species by incubating pancreatic tissues in the presence of polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) (1 U/ml) produced a decrease in nitrite levels (42%) and NO synthase (NOS) activity (50%) in diabetic but not in control samples. When NO production was blocked by N G-monomethyl-L-arginine (L-NMMA) (600 µM), SOD activity increased (15.21 ± 1.23 vs 24.40 ± 2.01 U/mg dry weight). The increase was abolished when the NO donor, spermine nonoate, was added to the incubating medium (13.2 ± 1.32). Lipid peroxidation was lower in diabetic tissues when PEG-SOD was added (0.40 ± 0.02 vs 0.20 ± 0.03 nmol/mg protein), and when L-NMMA blocked NOS activity in the incubating medium (0.28 ± 0.05); spermine nonoate (100 µM) abolished the decrease in lipoperoxide level (0.70 ± 0.02). We conclude that removal of oxygen species produces a decrease in pancreatic NO and NOS levels in STZ-treated rats. Moreover, inhibition of NOS activity produces an increase in SOD activity and a decrease in lipoperoxidation in diabetic pancreatic tissues. Oxidative stress and NO pathway are related and seem to modulate each other in acute STZ-induced diabetic pancreas in the rat.

Intravenous dipyrone for the acute treatment of episodic tension-type headache: A randomized, placebo-controlled, double-blind study

Acute headaches are responsible for a significant percentage of the case load at primary care units and emergency rooms in Brazil. Dipyrone (metamizol) is easily available in these settings, being the most frequently used drug. We conducted a randomized, placebo-controlled, double-blind study to assess the effect of dipyrone in the acute treatment of episodic tension-type headache. Sixty patients were randomized to receive placebo (intravenous injection of 10 ml saline) or 1 g dipyrone in 10 ml saline. We used seven parameters of analgesic evaluation. The patients receiving dipyrone showed a statistically significant improvement (P<0.05) of pain compared to placebo up to 30 min after drug administration. The therapeutic gain was 30% in 30 min and 40% in 60 min. The number of patients needed to be treated for at least one to have benefit was 3.3 in 30 min and 2.2 in 60 min. There were statistically significant reductions in the recurrence (dipyrone = 25%, placebo = 50%) and use of rescue medication (dipyrone = 20%, placebo = 47.6%) for the dipyrone group. Intravenous dipyrone is an effective drug for the relief of pain in tension-type headache and its use is justified in the emergency room setting.

Immunological effects of donor lymphocyte infusion in patients with chronic myelogenous leukemia relapsing after bone marrow transplantation

Allogeneic bone marrow transplantation (alloBMT) is the only curative therapy for chronic myelogenous leukemia (CML). This success is explained by the delivery of high doses of antineoplastic agents followed by the rescue of marrow function and the induction of graft-versus-leukemia reaction mediated by allogeneic lymphocytes against host tumor cells. This reaction can also be induced by donor lymphocyte infusion (DLI) producing remission in most patients with CML who relapse after alloBMT. The immunological mechanisms involved in DLI therapy are poorly understood. We studied five CML patients in the chronic phase, who received DLI after relapsing from an HLA-identical BMT. Using flow cytometry we evaluated cellular activation and apoptosis, NK cytotoxicity, lymphocytes producing cytokines (IL-2, IL-4 and IFN-gamma), and unstimulated (in vivo) lymphocyte proliferation. In three CML patients who achieved hematological and/or cytogenetic remission after DLI we observed an increase of the percent of activation markers on T and NK cells (CD3/DR, CD3/CD25 and CD56/DR), of lymphocytes producing IL-2 and IFN-gamma, of NK activity, and of in vivo lymphocyte proliferation. These changes were not observed consistently in two of the five patients who did not achieve complete remission with DLI. The percent of apoptotic markers (Fas, FasL and Bcl-2) on lymphocytes and CD34-positive cells did not change after DLI throughout the different study periods. Taken together, these preliminary results suggest that the therapeutic effect of DLI in the chronic phase of CML is mediated by classic cytotoxic and proliferative events involving T and NK cells but not by the Fas pathway of apoptosis.

Päätöksenteon haasteet pelastuslaitosten onnettomuuksien ehkäisyn osastoilla

Työn tavoitteena on selvittää, millaisia haasteita kohdataan pelastuslaitosten onnettomuuksien ehkäisyn osastoilla päätöksiä tehtäessä ja lisäksi selvittää asioita, jotka vaikuttavat päätöksentekoon. Tutkimus suoritettiin kyselytutkimuksena, johon osallistui pelastusviranomaisia ympäri Suomen. Tutkimuksessa kävi ilmi, että lähtökohdat laadukkaalle päätöksenteolle ovat pääsääntöisesti kunnossa. Säädösten osalta pelastuslaissa ja siihen liittyvissä asetuksissa asiat on esitetty paremmin kuin rakentamisen paloturvallisuuteen liittyvissä määräyksissä ja ohjeissa. Jotta päätöksenteko olisi helpompaa ja päätökset yhdenmukaisia valtakunnallisesti, yhteistyöhön ja kumppanuusverkoston toimintaan kannattaa panostaa myös jatkossa.

The selective and non-selective cyclooxygenase inhibitors valdecoxib and piroxicam induce the same postoperative analgesia and control of trismus and swelling after lower third molar removal

We compared the clinical efficacy of orally administered valdecoxib and piroxicam for the prevention of pain, trismus and swelling after removal of horizontally and totally intrabony impacted lower third molars. Twenty-five patients were scheduled to undergo removal of symmetrically positioned lower third molars in two separate appointments. Valdecoxib (40 mg) or piroxicam (20 mg) was administered in a double-blind, randomized and crossed manner for 4 days after the surgical procedures. Objective and subjective parameters were recorded for comparison of postoperative courses. Both agents were effective for postoperative pain relief (N = 19). There was a similar mouth opening at suture removal compared with the preoperative values (86.14 ± 4.36 and 93.12 ± 3.70% of the initial measure for valdecoxib and piroxicam, respectively; ANOVA). There was no significant difference regarding the total amount of rescue medication taken by the patients treated with valdecoxib or piroxicam (173.08 ± 91.21 and 461.54 ± 199.85 mg, respectively; Wilcoxon test). There were no significant differences concerning the swelling observed on the second postoperative day compared to baseline measures (6.15 ± 1.84 and 8.46 ± 2.04 mm for valdecoxib and piroxicam, respectively; ANOVA) or on the seventh postoperative day (1.69 ± 1.61 and 2.23 ± 2.09 mm for valdecoxib and piroxicam, respectively; ANOVA). The cyclooxygenase-2 selective inhibitor valdecoxib is as effective as the non-selective cyclooxygenase inhibitor piroxicam for pain, trismus and swelling control after removal of horizontally and totally intrabony impacted lower third molars.

Preparation and cytotoxicity of cisplatin-containing liposomes

We encapsulated cisplatin into stealth pH-sensitive liposomes and studied their stability, cytotoxicity and accumulation in a human small-cell lung carcinoma cell line (GLC4) and its resistant subline (GLC4/CDDP). Since reduced cellular drug accumulation has been shown to be the main mechanism responsible for resistance in the GLC4/CDDP subline, we evaluated the ability of this new delivery system to improve cellular uptake. The liposomes were composed of dioleoylphosphatidylethanolamine (DOPE), cholesteryl hemisuccinate (CHEMS), and distearoylphosphatidylethanolamine-polyethyleneglycol 2000 (DSPE-PEG2000) and were characterized by determining the encapsulation percentage as a function of lipid concentration. Among the different formulations, DOPE/CHEMS/DSPE-PEG liposomes (lipid concentration equal to 40 mM) encapsulated cisplatin more efficiently than other concentrations of liposomes (about 20.0%, mean diameter of 174 nm). These liposomes presented good stability in mouse plasma which was obtained using a 0.24-M EDTA solution (70% cisplatin was retained inside the liposomes after 30 min of incubation). Concerning cytotoxic effects, they are more effective (1.34-fold) than free cisplatin for growth inhibition of the human lung cancer cell line A549. The study of cytotoxicity to GLC4 and GLC4/CDDP cell lines showed similar IC50 values (approximately 1.4 µM), i.e., cisplatin-resistant cells were sensitive to this cisplatin formulation. Platinum accumulation in both sensitive and resistant cell lines followed the same pattern, i.e., approximately the same intracellular platinum concentration (4.0 x 10-17 mol/cell) yielded the same cytotoxic effect. These results indicate that long-circulating pH-sensitive liposomes, also termed as stealth pH-sensitive liposomes, may present a promising delivery system for cisplatin-based cancer treatment. This liposome system proved to be able to circumvent the cisplatin resistance, whereas it was not observed when using non-long-circulating liposomes composed of phosphatidylcholine, phosphatidylserine, and cholesterol.

Direct costs of asthma in Brazil: a comparison between controlled and uncontrolled asthmatic patients

Asthma is a common chronic illness that imposes a heavy burden on all aspects of the patient's life, including personal and health care cost expenditures. To analyze the direct cost associated to uncontrolled asthma patients, a cross-sectional study was conducted to determine costs related to patients with uncontrolled and controlled asthma. Uncontrolled patient was defined by daytime symptoms more than twice a week or nocturnal symptoms during two consecutive nights or any limitations of activities, or need for relief rescue medication more than twice a week, and an ACQ score less than 2 points. A questionnaire about direct cost stratification in health services, including emergency room visits, hospitalization, ambulatory visits, and asthma medications prescribed, was applied. Ninety asthma patients were enrolled (45 uncontrolled/45 controlled). Uncontrolled asthmatics accounted for higher health care expenditures than controlled patients, US$125.45 and US$15.58, respectively [emergency room visits (US$39.15 vs US$2.70) and hospitalization (US$86.30 vs US$12.88)], per patient over 6 months. The costs with medications in the last month for patients with mild, moderate and severe asthma were US$1.60, 9.60, and 25.00 in the uncontrolled patients, respectively, and US$6.50, 19.00 and 49.00 in the controlled patients. In view of the small proportion of uncontrolled subjects receiving regular maintenance medication (22.2%) and their lack of resources, providing free medication for uncontrolled patients might be a cost-effective strategy for the public health system.

Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity

This review addresses the mechanisms of methylmercury (MeHg)-induced neurotoxicity, specifically examining the role of oxidative stress in mediating neuronal damage. A number of critical findings point to a central role for astrocytes in mediating MeHg-induced neurotoxicity as evidenced by the following observations: a) MeHg preferentially accumulates in astrocytes; b) MeHg specifically inhibits glutamate uptake in astrocytes; c) neuronal dysfunction is secondary to disturbances in astrocytes. The generation of reactive oxygen species (ROS) by MeHg has been observed in various experimental paradigms. For example, MeHg enhances ROS formation both in vivo (rodent cerebellum) and in vitro (isolated rat brain synaptosomes), as well as in neuronal and mixed reaggregating cell cultures. Antioxidants, including selenocompounds, can rescue astrocytes from MeHg-induced cytotoxicity by reducing ROS formation. We emphasize that oxidative stress plays a significant role in mediating MeHg-induced neurotoxic damage with active involvement of the mitochondria in this process. Furthermore, we provide a mechanistic overview on oxidative stress induced by MeHg that is triggered by a series of molecular events such as activation of various kinases, stress proteins and other immediate early genes culminating in cell damage.