This doctoral dissertation work strived to contribute to the ever expanding knowledge about the mechanisms of polychlorinated biphenyl (PCB) toxicity using dietary strategies. PCBs are a family of persistent environmental pollutants with a wide range of toxicity. The toxicity of PCBs is largely dependent on the congener's chlorination pattern. Of particular interest to this work was 3,3',4,4',5-pentachlorobiphenyl (PCB 126), the most potent of the dioxin-like PCB congeners. I hypothesized that in vivo PCB 126 toxicity will be ameliorated by dietary selenium supplementation, lowered dietary copper, and dietary N-acetylcysteine (NAC) supplementation. Dioxin-like PCBs are known for diminishing hepatic selenium and selenium-dependent glutathione peroxidase (SeGPx), an antioxidant enzyme. In the first study, PCB 126 caused a dose-dependent decrease in hepatic selenium and SeGPx. Supplemental dietary selenium significantly increased hepatic selenium and SeGPx, and decreased incidence of apoptosis in these rats. The results from this study support that selenium plays a protective role, and differences in liver injuries of these rats may be reflected in their selenium status. The dose-dependent increase in hepatic copper caused by PCB 126 was a subject of interest and concern in the next study. Lowering dietary copper levels without negatively affecting the function of the essential antioxidant enzyme copper zinc superoxide dismutase did not result in reduction of PCB 126-induced toxicity. Copper metabolism was unlikely a main target of PCB 126 toxicity as increasing dietary copper did not significantly increase hepatic copper levels. Hepatic copper is highly regulated and likely does not play a significant role in PCB 126-induced toxicity. The effectiveness of NAC on restoring glutathione status and reducing PCB 126 toxicity was tested in the final study. While NAC did not restore glutathione status, NAC supplemented rats had significantly reduced severity of PCB 126-induced liver status. The results of this study are consistent with the theory that NAC has a glutathione-independent effect in improving mitochondrial energy metabolism. It also suggests that PCB 126-induced mitochondrial metabolic disruption of the liver is of greater concern than oxidative stress.

This study determined the effect of N-acetylcysteine (NAC) supplementation on recovery of strength following eccentric muscle injury. Female subjects (n = 21, age = 20.7 ± .10 yr, weight = 68.05 ± 10.3 kg, height = 1.69 ± .07 m) performed one bout of eccentric exercise involving the forearm flexor muscles. Subjects were given a placebo (food-grade cellulose; n = 10) or NAC supplement (10 mg·kg-1 bw·d-1; n = 11) for 7D prior to and 14D following the exercise bout. Maximal Voluntary Contraction (MVC) torque, muscle soreness, range of motion (ROM), and arm circumference were measured at pre-exercise, immediately post-exercise, and at 1D, 3D, 7D and 10D post-exercise. In addition, serum interleukin-6 (IL-6), serum creatine kinase (CK), and serum glutathione were measured. Subjects also completed a food frequency questionnaire to determine the antioxidant content of their diet. There was no difference in the loss and subsequent recovery of muscular strength between the placebo and NAC group immediately post-exercise (26.93 ± 6.4 vs. 24.95 ±9.4 Nm), 1D (27.83 ± 5.7 vs. 26.9 ± 8.5 Nm), 3D (38.35 ± 6.7 vs. 34.69 ± 10.2 Nm), 7D (46.9 ± 8.8 vs. 42.5 ± 11.8 Nm), or 10D (57.83 ± 11.7 vs. 52.92 ± 14.3 Nm) post-exercise (p = .274). In addition, there was no difference in muscle soreness (p = .752), arm circumference (p = .535), ROM (p = .539), serum CK (p = .449), serum glutathione (p = .967), or serum IL-6 (p = .360) at any time point. Scores on the food frequency questionnaire demonstrated that dietary antioxidant intake was not different between groups (41.04 ± 8.04 vs. 33.01 ± 12.6; p = .054). In conclusion, a bout of eccentric forearm flexor exercise resulted in muscle injury and a significant decrease in subjects’ ability to produce force. Supplementation with NAC had no effect on recovery of strength, arm circumference, ROM, serum CK, serum IL-6, or serum glutathione at any time point following the exercise bout. These results demonstrate that NAC has no effect on recovery of strength following eccentric muscle injury.

Class of 2010 Abstract / OBJECTIVES: The purpose of this study was to determine the incidence of contrast induced nephropathy (CIN) for patients receiving a pre-hydration regimen to prevent CIN. METHODS: This was a descriptive retrospective chart review study. Charts were reviewed from Banner Boswell Medical Center and a nephrologist’s office in Sun City, Arizona. RESULTS: There were a total of 12 patients included in the study. The population after completetion of chart reviews consisted of 6 male patients and 6 female patients. The age range of the patients included was 54-90 years old. CIN occurred in zero of the twelve patients. Half of the 12 patients had a decrease in serum creatinine ranging from 0.1- 0.6 mg/dL, 24-48 hours post-diagnostic procedure. CONCLUSIONS: There was no incidence of CIN after the 12 patients received the specific protocol. This study demonstrates the potential for this regimen as a pre-hydration option for individuals undergoing procedures in which radiocontrast is necessitated. A prospective observational study with a larger sample size would be warranted to determine the safety and efficacy of the protocol and increase the validity of the results of this descriptive study.

Maternal stress during pregnancy is associated with increased risk of psychiatric disorders in offspring, but embryonic brain mechanisms disrupted by prenatal stress are not fully understood. Our lab has shown that prenatal stress delays inhibitory neural progenitor migration. Here, we investigated redox dysregulation as a mechanism for embryonic cortical interneuron migration delay, utilizing direct manipulation of pro- and anti-oxidants and a mouse model of maternal repetitive restraint stress starting on embryonic day 12. Time-lapse, live-imaging of migrating GABAergic interneurons showed that normal tangential migration of inhibitory progenitor cells was disrupted by the pro-oxidant, hydrogen peroxide. Interneuron migration was also delayed by in utero intracerebroventricular rotenone. Prenatal stress altered glutathione levels and induced changes in both activity of antioxidant enzymes and expression of redox-related genes in the embryonic forebrain. Assessment of dihydroethidium (DHE) fluorescence after prenatal stress in ganglionic eminence, the source of migrating interneurons, showed increased levels of DHE oxidation. Maternal antioxidants (N-acetylcysteine and astaxanthin) normalized levels of DHE oxidation in ganglionic eminence, and ameliorated the migration delay caused by prenatal stress. In adult male offspring, prenatally-stressed mice exhibited anxiety-like behavior on the elevated plus maze, impaired motor learning on the rotarod, cognitive flexibility on the water T-maze task, and deficits in sensorimotor gating in the pre-pulse inhibition task. Prenatally-stressed adult female offspring showed anxiety-like behavior, deficits in sociability and impaired motor learning. Maternal antioxidants prevented anxiety-like behaviors and improved sensorimotor gating in both sexes, and improved habitual learning and cognitive flexibility in adult female mice. Lastly, prenatal stress led to increases in PV+/GAD67+ cell ratios in mFC in male mice, but decreases in female mice, and antioxidant treatments eliminated those differences. Hippocampal GAD67+ cell densities were reduced by prenatal stress and restored by astaxanthin in male mice, and PV+/GAD67+ cell ratio was reduced by prenatal stress and partially restored by N-acetylcysteine in female mice. GAD67+ cell densities across regions correlated significantly with anxiety-like behavior in both male and female mice and social behavior in female mice. Through convergent redox manipulations, delayed interneuron migration after prenatal stress was found to critically involve redox dysregulation. Redox biology during prenatal periods may be a target for protecting brain development.

Orientador: Sisi Marcondes Paschoal / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-23T16:04:16Z (GMT). No. of bitstreams: 1 Tangerino_DeboraJulianadosAnjos_M.pdf: 666295 bytes, checksum: d40f37f273e761c768f098ca04d15d89 (MD5) Previous issue date: 2013 / Resumo: A sepse caracteriza-se por uma reação inflamatória sistêmica e um quadro de estresse oxidativo em decorrência da grande formação de espécies reativas de oxigênio (EROs). Há trabalhos que mostram que as plaquetas são importantes neste quadro inflamatório, mas seu verdadeiro papel na sepse ainda não está bem elucidado. Portanto, o objetivo do presente trabalho foi avaliar o efeito temporal do uso do antioxidante N-acetilcisteína (NAC) na resposta inflamatória e na atividade plaquetária em modelo de sepse induzido por lipopolissacarídeo (LPS). Para tanto, ratos controle foram injetados com salina (300 ?l, i.p.) ou NAC (150 mg/kg, i.p.), enquanto os tratados foram injetados com LPS de E. coli (1 mg/kg, i.p.) ou com NAC 30 min ou 6h após a injeção de LPS. Após 48h da injeção de LPS o sangue foi coletado. O número de leucócitos totais e plaquetas foi determinado no sangue periférico. A concentração plasmática de TNF-? foi determinada utilizando kit comercial de ELISA. A agregação plaquetária foi avaliada em agregômetro de dois canais. A determinação de EROs em plaquetas foi feita por citometria de fluxo e a de GMPc por imunoensaio. A determinação da atividade da superóxido dismutase (SOD), glutationa peroxidase (GPx) e glutationa redutase (GR) foi feita através de kits comerciais. O LPS aumentou o número de leucócitos totais e reduziu o de plaquetas no sangue periférico. A NAC, 30 min ou 6h após a injeção de LPS, levou a contagem destas células para números semelhantes ao do grupo injetado com salina ou somente com NAC. A concentração plasmática aumentada de TNF-? nos ratos injetados com LPS foi reduzida por NAC para valores próximos aos encontrados no grupo salina. A agregação plaquetária induzida por ADP (10 ?) não foi afetada por NAC, mas foi 50% menor em ratos tratados com LPS. A inibição da agregação plaquetária foi revertida pela injeção de NAC 30 min ou 6h após a injeção de LPS. O LPS aumentou 2,2 vezes os níveis de GMPc em plaquetas estimuladas com ADP quando comparado com o grupo injetado com salina, o qual foi prevenido por NAC, quer em 30 min ou 6h após a injeção de LPS. Os níveis de GMPc em plaquetas de ratos injetados com NAC foram 45% menores do que os do grupo salina. A produção aumentada de EROs em plaquetas ativadas de ratos injetados com LPS foi reduzida por NAC para níveis semelhantes aos dos controle. A NAC reduziu significativamente a formação de EROs em plaquetas em comparação com o grupo salina. A atividade enzimática da SOD em plaquetas ativadas foi reduzida em 35% por NAC em comparação com o grupo salina. O LPS aumentou, discretamente, a atividade da SOD em plaquetas, sendo este prevenido pelo tratamento com NAC. Diferente do observado com SOD, as atividades enzimáticas da GPx e da GR em plaquetas ativadas foram significativamente aumentadas pelo LPS. A NAC não modificou a atividade da GPx e da GR em comparação com o grupo salina, mas reduziu cerca de 41% e 61% a atividade da GPx e GR, respectivamente, em plaquetas do grupo injetado com LPS. Nossos resultados mostraram que a NAC previne e reverte os efeitos do tratamento de ratos com LPS na atividade plaquetária. O restabelecimento da agregação plaquetária, dos níveis de GMPc e EROs intraplaquetário podem ter sido resultado de uma ação direta de NAC nas plaquetas e/ou em decorrência da melhora do quadro inflamatório do animal / Abstract: Sepsis is an oxidative stress condition characterized by a systemic inflammatory reaction. It has been demonstrated that platelets are important in this inflammatory condition, but their real role in sepsis has not been well elucidated yet. Therefore, the aim of this study was to evaluate the temporal effect of the use of the antioxidant Nacetylcysteine (NAC) in the inflammatory response and platelet activity in a model of sepsis induced by lipopolysaccharide (LPS). Control rats were injected with saline (300 ?l, i.p.) or NAC (150 mg/kg, i.p.), while those treated were injected with LPS from E. coli (1 mg/kg, i.p.) or with NAC 30 min or 6 h after LPS injection. Blood was collected 48 h after LPS injection. Total leukocytes and platelets number was determined in peripheral blood. The plasma concentration of TNF-? was determined using commercial ELISA kit. Platelet aggregation was measured in two-channel aggregometer. Determination of reactive oxygen species (ROS) in platelets was performed by flow cytometry and cGMP by immunoassay. Enzymatic activity of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) was determinated using commercial kits. LPS increased the total leukocytes number and reduced platelets in peripheral blood. NAC, 30 min or 6 h after LPS injection, brought the cell counts to the similar values of rats injected with saline or with NAC. The increased plasma concentrations of TNF-? in rats injected with LPS was reduced by NAC to values close to those found in the saline group. ADP (10 ?M)-induced platelet aggregation was unaffected by NAC but was 50% lower in rats treated with LPS. Inhibition of platelet aggregation was reversed by the injection of NAC 30 min or 6 h after LPS injection. LPS increased intraplatelet cGMP levels by 2.2-fold compared to the group injected with saline, which was prevented by NAC either 30 min or 6 hours after LPS injection. cGMP levels in activated platelets of rat injected with NAC were 45% lower than those of the saline group. The increased production of ROS in activated platelets from rat injected with LPS was reduced by NAC to levels similar to the control. NAC significantly reduced the formation of ROS in platelets compared to the saline group. SOD activity in stimulated platelets was reduced 35% by NAC compared to the saline group. LPS slightly increased SOD activity in platelets, which is prevented by treatment with NAC. Different from that observed with SOD, the enzyme activities of GPx and GR in activated platelets were significantly increased by LPS. The NAC did not modify the activity of GPx and GR compared with the saline group, but decreased by 41% and 61% the GPx and GR activities, respectively, in platelets of LPS-injected group. Our results showed that NAC prevents and reverses the effects of in vivo LPS on platelet activity. Restoration of platelet aggregation and of intraplatelet cGMP and ROS levels of LPS-injected rats may be caused by a direct action of NAC in platelets or by the improvement of inflammatory condition in the animal / Mestrado / Farmacologia / Mestra em Farmacologia

Class of 2014 Abstract / Specific Aims: To determine the cost of treatment of oral and intravenous n-acetylcysteine (IV NAC) in acute acetaminophen (APAP) toxicity using the length of treatment and length of hospital stay. Methods: A retrospective chart review of Arizona Poison and Drug Information Center electronic records from 2009-2012 and January-June 2013 were evaluated. The following information was collected: age, sex, use oral or intravenous NAC, length of treatment, length of hospital stay (intensive care unit (ICU) and non-ICU) and use of antiemetic. The mean length of stay (MLOS) was calculated for each group as well as the cost of IV and oral NAC. These means were then compared using t-test for independent groups to test for significance. The average total cost of IV and oral NAC treatment was calculated by using monetary values from primary literature. A sensitivity analysis was performed to test the possible effects of an increase or decrease of the final costs by 5 to 10%. Main Results: Patients (≥18 yrs) being treated with IV or oral NAC for acute APAP toxicity (≤8 hours prior to ingestion) were included in this study. A total of 47 patients met the inclusion criteria. Length of hospital stay was shorter in patients receiving IV NAC (42.5% 24-24hr; 37.5% 48-72hr) compared to patients receiving oral NAC (28.6% 48-72hr, 71.4% >72hrs; p<0.001). Total cost of ICU/non-ICU stay in patients receiving IV NAC ($8,720/$3010) was less than patients receiving oral NAC ($12,321/$4703); however, cost of IV NAC-extended (37hrs) in ICU/non-ICU ($13,153/$5535) was greater than oral NAC. The sensitivity analysis performed demonstrated that an increase or a decrease by 5 to 10% in change of cost does not affect our final conclusion. Conclusion: The cost of treatment of IV NAC is lower due to shorter LOS of patients treated with IV NAC (p<0.001). However, when an extended course of treatment is medically necessary for patients on IV NAC then the cost of treatment with IV NAC exceeds the cost of treatment with oral NAC.

Due to the need for concurrent use of N-acetylcysteine (NAC) and ondansetron in the event of acetaminophen overdose, a Y-site intravenous (IV) apparatus for these drugs would be practical. It is known that nausea and vomiting are common side effects of both acetaminophen overdose and NAC administration. Current standard patient care using NAC involves interruption of IV NAC infusion to give an IV bolus dose of ondansetron, which creates an unnecessary opportunity for healthcare staff errors and patient complications. To evaluate the IV compatibility of NAC and ondansetron, medical grade tubing was connected via a closed-circuit IV pump with separate channels. Doses of NAC were circulated in individual channels based on weight-based dosing protocols (30-kg and 100-kg patient does). Ondansetron (4 mg) was introduced into the flow of NAC using the Y-site. Samples of the circulated solutions were gathered in triplicate at time points of 10, 20, and 30 minutes after combination of ondansetron and NAC. Concentrations of NAC were quantified using a validated high performance liquid chromatography (HPLC) method with ultraviolet (UV) detection. Once the collected samples underwent HPLC-UV analysis, data was produced that showed promise for compatibility between ondansetron and NAC with Y-site infusions. Comparison of NAC concentrations for the channels with and without ondansetron yielded no statistically significant difference between the treatments (p-value of 0.05). From this experiment, we concluded that introduction of ondansetron into the flow of NAC IV would not impact NAC concentration. As mentioned before, this study was conducted using only two doses in vitro, which may be a point for further exploration of a varied number of N-acetylcysteine doses.

Master of Science / Department of Kinesiology / Thomas J. Barstow / The accumulation of reactive oxygen species (ROS) has been linked to the development of muscular fatigue. Antioxidant administration has the potential to counteract the increased levels of ROS, leading to improvements in performance. N-acetylcysteine (NAC), a nonspecific antioxidant, is especially promising due to its ability to support the biosynthesis of glutathione, one of the primary endogenous antioxidants. Despite this, the effects of NAC on time to fatigue appear to be dependent upon the exercise intensity, with the more pronounced effects evident at submaximal exercise intensities. The purpose of this study was to determine the effects of an acute dose of NAC on whole body fatigue, critical power (CP) and W’ during high-intensity exercise. It was hypothesized that pretreatment with NAC would result in (1) an increase in time to fatigue (TTF), CP and W’, (2) NAC administration would attenuate changes in the EMG responses indicative of fatigue, and (3) speeding of the kinetics of the primary phase of VO2 and a reduction in the slow component. Seven healthy, active males (age: 21.4 ± 1.6 years, weight: 89.1 ± 11.0 kg, height: 183 ± 5 cm) completed an incremental ramp test until exhaustion for the determination of peak VO2 and power. Four tests were subsequently performed at power outputs corresponding to 80, 90, 100, and 110% Pmax under NAC and placebo (PLA) conditions. NAC resulted in a significant increase in [tGSH] in red blood cells compared to baseline and PLA condition. TTF was significantly increased only in the 80% Pmax trial (p = 0.033). CP was also significantly higher with NAC (NAC: 232 ± 28 W vs PLA: 226 ± 31 W; p = 0.032), but W’ showed a tendency to decrease (NAC: 15.5 ± 3.8 kJ vs W’: 16.4 ± 4.5 kJ). The change in W’ was negatively related to CP (r = -0.96), indicating that the increase in CP was associated with a decrease in W’. EMG analysis revealed a tendency for MdPF and RMS to demonstrate less of a change with NAC. There were no significant differences in VO2 kinetics, but an inverse relationship was observed between the change in τp and the magnitude of the slow component expressed both in absolute terms (r = -0.632, p = 0.007) and as a gain (r = -0.751, p = 0.0005). We conclude that NAC was effective in delaying fatigue and improving exercise performance at 80% peak power, although the exact mechanisms are still unclear.

Thesis (MSc)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: This thesis aims to determine whether supplementation with a grape-seed derived antioxidant, oligomeric proanthocyanidin (PCO) or the glutathione precursor, N-acetylcysteine (NAC) may prove beneficial as treatment for exercise induced muscle damage (EIMD) in athletes. In this double-blind cohort study, 21 healthy, uninjured male rugby-players in mid-season training phase, aged between 18 and 25 years were randomly divided into three treatment groups. Participants received 210 mg PCO, NAC or placebo treatment for 9 consecutive days. The study comprised a 6-day wash-out period (protocol days: -12 to -7), followed by a 6-day supplement loading period (protocol days: -6 to -1) a plyometric exercise intervention (protocol day 0) and continued supplementation for 2 days (protocol days: 1 to 2). The exercise intervention comprised 15 sets of 10 near maximal, vertical plyometric squat jumps. Blood samples and delayed onset of muscle soreness (DOMS) scores were collected on protocol days: -6, 0, 1 and 2. Assessments included serum creatine kinase (CK) activity, oxygen radical absorbance capacity (ORAC), malondialdehyde (MDA) and soluble vascular cell adhesion molecule-1 (sVCAM-1) concentrations over time as well as a differential circulating leukocyte count (neutrophils, lymphocytes, monocytes, eosinophils and basophils). Data analysis of CK activity revealed no significant differences between groups. However, PCO treatment prevented a significant peak in the CK response at 24 h (as seen in the placebo and NAC groups) when compared to baseline, pre and post readings (p<0.05). NAC supplementation significantly improved serum ORAC after the exercise intervention. By 48 h, serum ORAC had improved significantly from readings taken immediately post exercise (p<0.05) only in the NAC group. For all groups, absolute neutrophil counts peaked at 6 h post exercise from baseline or pre readings (p<0.05). In both NAC and placebo treated groups, neutrophil counts had decreased significantly in circulation by 24 h post exercise from the 6 h time-point (p<0.05). However, neutrophil counts only reached significantly lower levels by 48 h post exercise (p<0.05) in the group supplemented with PCO. The monocyte count also peaked significantly at 6 h post exercise when compared with other time-points before and after the exercise intervention (p<0.05) in all treatment groups. Neither antioxidant treatment significantly altered the responses of other leukocyte sub-populations, MDA or sVCAM-1 concentrations where main effects of plyometric exercise was evident. Although not statistically significant, a trend toward diminished sVCAM-1 expression with either antioxidant supplementation was apparent. These findings suggest that PCO supplementation (210mg/d) which includes a 7 day loading period may diminish plyometric EIMD by limiting (but not completely inhibiting) the neutrophil response. Secondary muscle damage may be prevented by partially blunting neutrophil infiltration, rather than only quenching free radicals released during the neutrophil oxidative burst. Furthermore, the finding that NAC supplementation improves serum ORAC only after exercise may provide added benefit when administered in combination with PCO. / AFRIKAANSE OPSOMMING: Hierde tesis is daarop gerig om vas te stel of aanvulling met ‘n druifsaadekstrak (DSE) gederiveerde antioksidant: pro-antosianiedoliese oligomeer (PSO), of die glutathione voorloopermolekule, N-asetielsistien (NAS) voordelig beskou kan word as behandeling vir atlete onderhewig aan spierskade veroorsaak deur oefening. Gedurende hierdie dubbelblinde kohort studie is 21 gesonde, manlike rugbyspelers sonder beserings tussen die ouderdom van 18 en 25 jaar in middel-seison fase ewekansig in drie behandelingsgroepe verdeel. Deelneemers het elk 210 mg PSO, NAS of placebo-aanvulling geneem vir nege agtereenvolgende dae. Die studie het bestaan uit ‘n 6-dag uitwasperiode (protokoldae: -12 tot -7), as ook ‘n 6-dag aanvullings periode (protokoldae: -6 tot -1), gevolg deur ‘n pliometriese oefeningsintervensie (protokol dag 0) en verdere aanvulling tot en met 2 dae na die oefening (protokol dae: 1 tot 2). Die oefeningsintervensie het 15 stelle van 10 naastenby maksimale, vertikale pliometriese hurkspronge behels. Bloedmonsters en vertraagde aanvang spierseerheid (VAS) tellings is op protokoldae: -6, 0, 1 en 2 geneem. Analiese het serum kreatien kinase (KK) aktiwiteit, suurstof radikaal absorpsie kapasiteit (SRAK), Malondialdahied (MDA) en oplospare vaskulêresel adhesie molekule-1 (oVAM-1) konsentrasie bepalings asook ‘n differentiële sirkulerende leukosiet seltelling ingesluit. KK aktiewiteit het geen merkwaardige verskil tussen groepe getoon nie. PSO aanvulling het wel gelei tot die voorkoming van ‘n merkwaardige piek in die KK response soos in die placebo en NAC behandelde groepe bevind is by die 24 h tydspunt in vergelyking met basislyn-, voor- en na-oefeningslesings (p<0.05). NAS het ‘n merkwaardige verbetering in serum SRAK getoon, maar eers teen 48 h na oefening. Slegs die NAS behandelde groep het op hierdie tydspunt ‘n betekenisvolle verbetering in SRAK getoon in vergelyking met lesings direk na oefening (p<0.05). Vir alle groepe is ‘n betekenisvolle toename in absolute neutrophiltellings waargeneem 6 h na oefening in vergelyking met basislyn- en vooroefeningslesings (p<0.05). Beide NAS en placebo-behandelde groepe het ‘n betekenisvolle afname in neutrophiltellings teen 24 h na oefening getoon in vergelyking met die 6 h tydspunt (p<0.05) maar met die PSO-behandelde groep word hierde afname eers teen 48 h waargeneem (p<0.05). Monosiettellings het in alle groepe 6 h na oefening ‘n betekinsvolle piek getoon (p<0.05). Waar slegs die hoofeffek van die pliometriese oefening betekenisvol was, het nie een van die twee antioksidant aanvullings ‘n merkwaardige verandering aan die respons van ander leukosiet sub-populasies, MDA of oVAM-1 konsentrasies getoon nie. Al kon statistiese beduidenheid nie bewys word nie, wil dit blyk dat ‘n verminderde oVAM-1 uitdrukking onstaan het in die geval van beide antioksidant-behandelde groepe. Tesame stel hierdie bevindinge voor dat PSO toediening (210mg/d) insluitende ‘n 7-dag aanvullingsperiode die vermoë verleen om die neutrophielrespons gedeeltelik te onderdruk (sonder om dit heeltemal te inhibeer) en sodoende spierskade verminder. Dus word verdere spierskade moontlik verlaag deur die voorkoming van neutrophil weefsel infiltrasie eerder as verwydering van reaktiewe spesies wat vrygestel word tydens oefening. Die bevinding dat NAS aanvulling serum SRAK eers na oefening merkwaardig verbeter, kan as voordelig beskou word, veral wanneer toegedien in samewerking met PSO om verdere spierskade te voorkom en herstelling vinniger te bewerkstellig.

Na infecção pelo HIV o equilíbrio entre antioxidantes e pró-oxidantes e a produção de citocinas encontram-se alterados, causando estresse oxidativo crônico. Presume-se que o estresse oxidativo crônico e a ativação do sistema imunológico favorecem a replicação do vírus através da ativação do NF-kB e a apoptose de células mononucleares do sangue periférico. O objetivo deste estudo foi avaliar o efeito da suplementação, durante 180 dias, com 600mg/dia de N-acetilcisteína (NAC), sobre a carga viral, os níveis de sub-populações de linfócitos, a viabilidade de linfócitos e sobre os níveis séricos de citocinas, proteínas, lipídeos, &#946;2 microglobulina e outros marcadores da ativação do sistema imunológico em pacientes assintomáticos, submetidos ao primeiro tratamento anti-retroviral. Participaram deste estudo, duplo cego controlado por placebo, que teve a duração de 180 dias, 30 indivíduos que iniciaram a terapia anti-retroviral. O grupo estudo foi constituído por 14 indivíduos que além do tratamento anti-retroviral foram suplementados com NAC, enquanto o grupo controle foi constituído por 16 indivíduos que além do tratamento anti-retroviral receberam placebo. Os marcadores avaliados foram determinados no dia anterior ao início do tratamento a que foram submetidos e após 60, 120 e 180 dias. Verificou-se aumento significante dos linfócitos CD4+, da relação CD4/CD8, de linfócitos viáveis, albumina, cisteína e glutationa, bem como diminuição significante dos níveis de TNF-&#945;, IL-8, haptoglobina e &#945;1-glicoproteína ácida, &#946;2-microglobulina, IgA e IgM, nos dois grupos estudados. Os níveis séricos de IL-6, colesterol total, LDL-colesterol, VLDL-colesterol e triglicerídeos não apresentaram alteração significante ao final deste estudo. Concluindo, a suplementação com 600 mg/dia de NAC, em pacientes submetidos ao tratamento anti-retroviral, não proporcionou benefícios adicionais àqueles decorrentes deste tratamento. / In HIV infection, the balance between antioxidants and pró-oxidants and the production of citokines are disturbed leading to a chronic state of oxidative stress and immune activation. It is presumed that HIV takes advantage of the proinflammatory and prooxidative environment to replicate through the NF-kB pathway leading to the apoptosis of peripheral blood mononuc1ear cells. The aim of this work was to study the effect of oral administration of N-acetylcysteine (NAC) 600 mg per day during 180 days on viral load, viability of lymphocytes, cytokines, proteins, lipids, &#946;2-microglobulin and other immune activation markers in asymptomatic patients under their first antiretroviral therapy. This was a double-blind, placebo-controlled study with 30 individuals who started antiretroviral therapy and were followed for 180 days. These individual were divided into two subgroups: the study group consisted of 14 participants who received NAC supplementation, whereas the control group had 16 individuals who received placebo. The studied markers were determined on the day before the beginning of treatment and after 60, 120 and 180 days of treatment. A significant increase was seen for CD4+ lymphocytes, the CD4/CD8 ratio, albumin, cysteine and glutathione; also, a significant reduction was found for levels of TNF-&#945;, IL-8, &#946;2 microglobulin, IgA, IgG, IgM, haptoglobin, and acid &#945;1-glycoprotein as a consequence of antiretroviral treatment. After 180 days of treatment, the levels of total protein, globulins and HDL-cholesterol presented significant alteration on1y in the control group, while the serum levels of IL-6, total cholesterol, LDL-cholesterol, VLDL-cholesterol and triglyceride did not show significant alteration at the end of the present study. In conclusion, the supplementation of HIV-positive patients with 600 mg/day of NAC did not bring additional benefits to those resulting from antiretroviral treatment.