Coping Strategies and Workplace Supports for Peers with Substance Use Disorders.

Introduction: Substance use disorder (SUD) peers provide support and navigation through a fragmented treatment system for people who use drugs (PWUD) and those in recovery. While barriers to peers' work are well established, from role ambiguity to stigma surrounding substance use, little research has focused on factors that facilitate peers' work. Methods: We conducted in-depth semi-structured interviews (N=20) with peers as part of an evaluation of a larger project related to the opioid crisis in Western New York. Participants were recruited from a regional peer network via flyers, emails, and a brief presentation. Interviews were conducted in person or by phone, audio recorded, and transcribed. Transcripts were analyzed using thematic content analysis. Results: Peers emphasized two factors: healthy personal coping strategies and strong workplace supports. Coping strategies included a sense of community, setting appropriate boundaries, and self-care routines. At the workplace, peers valued mental and emotional support, as well as professional relationships and organizational policies that made their work easier and supported self-care. For a few peers, professional relationships included advocating on behalf of PWUD by sharing personal experiences of SUD. Conclusions: Peers valued peer colleagues and peer-led organizations, noting how shared experiences of substance use and recovery enabled a unique support system. For peers who lack such support at work, the authors suggest peer networks as an alternative. We also recommend organizational policies and practices to facilitate peers' work, such as promoting peer input and feedback, but further research is needed to measure effects on peer retention and job satisfaction.

European Society of Paediatric Radiology abdominal imaging task force: recommendations for contrast-enhanced ultrasound and diffusion-weighted imaging in focal renal lesions in children.

Contrast-enhanced ultrasound (CEUS) and diffusion-weighted imaging (DWI) are safe, repeatable imaging techniques. The aim of this paper is to discuss the advantages, technical factors and possible clinical applications of these imaging tools in focal renal lesions in children.

Rejuvenation of allogenic red cells: benefits and risks.

BACKGROUND AND OBJECTIVES: To review preclinical and clinical studies that have evaluated the effects of red cell rejuvenation in vivo and in vitro and to assess the potential risks and benefits from their clinical use. MATERIALS AND METHODS: A systematic review and narrative synthesis of the intervention of red cell rejuvenation using a red cell processing solution containing inosine, pyruvate, phosphate and adenine. Outcomes of interest in vitro were changes in red cell characteristics including adenosine triphosphate (ATP), 2,3-diphosphoglycerate (2,3-DPG), deformability and the accumulation of oxidized lipids and other reactive species in the red cell supernatant. Outcomes in vivo were 24-h post-transfusion survival and the effects on oxygen delivery, organ function and inflammation in transfused recipients. RESULTS: The literature search identified 49 studies evaluating rejuvenated red cells. In vitro rejuvenation restored cellular properties including 2,3-DPG and ATP to levels similar to freshly donated red cells. In experimental models, in vivo transfusion of rejuvenated red cells improved oxygen delivery and myocardial, renal and pulmonary function when compared to stored red cells. In humans, in vivo 24-h survival of rejuvenated red cells exceeded 75%. In clinical studies, rejuvenated red cells were found to be safe, with no reported adverse effects. In one adult cardiac surgery trial, transfusion of rejuvenated red cells resulted in improved myocardial performance. CONCLUSION: Transfusion of rejuvenated red cells reduces organ injury attributable to the red cell storage lesion without adverse effects in experimental studies in vivo. The clinical benefits of this intervention remain uncertain.

Postpartum two- and three-dimensional ultrasound evaluation of anal sphincter complex in women with obstetric anal sphincter injury.

OBJECTIVE: To compare the sensitivity and specificity of two- (2D) and three- (3D) dimensional transperineal ultrasound (TPUS) and 3D endovaginal ultrasound (EVUS) with the gold standard 3D endoanal ultrasound (EAUS) in detecting residual defects after primary repair of obstetric anal sphincter injuries (OASIS). METHODS: External (EAS) and internal (IAS) anal sphincters were evaluated by the four ultrasound modalities in women with repaired OASIS. 2D-TPUS was evaluated in real-time, whereas 3D-TPUS, 3D-EVUS and 3D-EAUS volumes were evaluated offline by six blinded readers. The presence/absence of any tear in EAS or IAS was recorded and defects were scored according to the Starck system. Sensitivity, specificity and predictive values were calculated, using 3D-EAUS as reference standard. Inter- and intraobserver analyses were performed for all 3D imaging modalities. Association between patients' symptoms (Wexner score) and ultrasound findings (Starck score) was calculated. RESULTS: Images from 55 patients were analyzed. Compared with findings on 3D-EAUS, the agreement for EAS evaluation was poor for 3D-EVUS (κ = 0.01), fair for 2D-TPUS (κ = 0.30) and good for 3D-TPUS (κ = 0.73). The agreement for IAS evaluation was moderate for both 3D-EVUS (κ = 0.41) and 2D-TPUS (κ = 0.52) and good for 3D-TPUS (κ = 0.66). Good intraobserver (3D-EAUS, κ = 0.73; 3D-TPUS, κ = 0.78) and interobserver (3D-EAUS, κ = 0.68; 3D-TPUS, κ = 0.60) agreement was reported. Significant association between Starck and Wexner scores was found only for 3D-EAUS (Spearman's rho = 0.277, P = 0.04). CONCLUSIONS: 2D-TPUS and 3D-EVUS are not accurate modalities for the assessment of anal sphincters after repair of OASIS. 3D-TPUS shows good agreement with the gold standard 3D-EAUS and a high sensitivity in detecting residual defects. It, thus, has potential as a screening tool after primary repair of OASIS. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Randomized trial of red cell washing for the prevention of transfusion-associated organ injury in cardiac surgery.

BACKGROUND: Experimental studies suggest that mechanical cell washing to remove pro-inflammatory components that accumulate in the supernatant of stored donor red blood cells (RBCs) might reduce inflammation and organ injury in transfused patients. METHODS: Cardiac surgery patients at increased risk of large-volume RBC transfusion were eligible. Participants were randomized to receive either mechanically washed allogenic RBCs or standard care RBCs. The primary outcome was serum interleukin-8 measured at baseline and at four postsurgery time points. A mechanism substudy evaluated the effects of washing on stored RBCs in vitro and on markers of platelet, leucocyte, and endothelial activation in trial subjects. RESULTS: Sixty adult cardiac surgery patients at three UK cardiac centres were enrolled between September 2013 and March 2015. Subjects received a median of 3.5 (interquartile range 2-5.5) RBC units, stored for a mean of 21 ( sd 5.2) days, within 48 h of surgery. Mechanical washing reduced concentrations of RBC-derived microvesicles but increased cell-free haemoglobin concentrations in RBC supernatant relative to standard care RBC supernatant. There was no difference between groups with respect to perioperative serum interleukin-8 values [adjusted mean difference 0.239 (95% confidence intervals -0.231, 0.709), P =0.318] or concentrations of plasma RBC microvesicles, platelet and leucocyte activation, plasma cell-free haemoglobin, endothelial activation, or biomarkers of heart, lung, or kidney injury. CONCLUSIONS: These results do not support a hypothesis that allogenic red blood cell washing has clinical benefits in cardiac surgery. CLINICAL TRIAL REGISTRATION: ISRCTN 27076315.

Apolipoprotein E-ε4 deficiency and cognitive function in hepatitis C virus-infected patients.

Hepatitis C virus (HCV) causes not only liver damage in certain patients but can also lead to neuropsychiatric symptoms. Previous studies have shown that the type 4 allele of the gene for apolipoprotein E (APOE) is strongly protective against HCV-induced damage in liver. In this study, we have investigated the possibility that APOE genotype is involved in the action of HCV in brain. One hundred HCV-infected patients with mild liver disease underwent a neurological examination and a comprehensive psychometric testing of attention and memory function. In addition, patients completed questionnaires for the assessment of fatigue, health-related quality of life and mood disturbances. Apolipoprotein E gene genotyping was carried out on saliva using buccal swabs. The APOE-ε4 allele frequency was significantly lower in patients with an impairment of working memory, compared to those with a normal working memory test result (P = 0.003). A lower APOE-ε4 allele frequency was also observed in patients with definitely altered attention ability (P = 0.008), but here, the P-value missed the level of significance after application of the Bonferroni correction. Our data suggest that the APOE-ε4 allele is protective against attention deficit and especially against poor working memory in HCV-infected subjects with mild liver disease. Considering the role of apolipoprotein E in the life cycle of the virus, the findings shed interesting new light upon possible pathomechanisms behind the development of neuropsychiatric symptoms in hepatitis C infection.

Formation of Highly Ordered Spherical Aggregates from Drying Microdroplets of Colloidal Suspension.

The formation of highly ordered spherical aggregates of silica nanoparticles by the evaporation of single droplets of an aqueous colloidal suspension levitated (confined) in the electrodynamic quadrupole trap is reported. The transient and final structures formed during droplet evaporation have been deposited on a silicon substrate and then studied with SEM. Various successive stages of the evaporation-driven aggregation of nanoparticles have been identified: formation of the surface layer of nanoparticles, formation of the highly ordered spherical structure, collapse of the spherical surface layer leading to the formation of densely packed spherical aggregates, and rearrangement of the aggregate into the final structure of a stable 3D quasi-crystal. The evaporation-driven aggregation of submicrometer particles in spherical symmetry leads to sizes and morphologies of the transient and final structures significantly different than in the case of aggregation on a substrate. The numerical model presented in the article allows us to predict and visualize the observed aggregation stages and their dynamics and the final aggregates observed with SEM.

Mass marking of Leuciscus idus larvae using Artemia salina as a vector of fluorescent dyes.

A method for the mass marking of ide Leuciscus idus larvae by feeding them Artemia salina nauplii that were immersed in different solutions of alizarin red S, tetracycline hydrochloride and calcein was tested. The best quality marks were obtained after feeding fish for 4 days with nauplii that had been immersed in 200 mg l(-1) alizarin red S.

Carbon matrix based magnetic nanocomposites for potential biomedical applications.

It was found that by varying the pyrolysis temperature of the polymeric precursor, carbon matrix magnetic nanocomposites with different constitution and fractions of magnetic component were made. X-ray diffraction, transmission electron microscopy and Raman spectroscopy revealed the presence of nanocrystallites (NCs) of Co, Fe3C and Ni embedded in porous, partially-graphitized carbon matrix. Vibrating sample magnetometer measurements enabled to determine the correlation between NCs size distribution and magnetic properties. The magnetic studies confirmed that the coercivity, saturation and remanent magnetizations, as well as fraction of the magnetic component depend on the pyrolysis temperature. The Co#C and Fe3C#C composites exhibited ferromagnetic behavior with a remanent to saturation magnetization (M(R)/M(S)) ratio ranging from 0.25 to 0.3, whereas in the Ni containing samples a relatively small M(R)/M(S) ratio point to significant contribution of superparamagnetic interactions. As the carbon matrix magnetic nanocomposites are proposed for biomedical application the basic cytotoxicity test were performed to evaluate a potential toxic effect of the materials on MG-63 cells line.

Lithium treatment of a bipolar patient with Wilson's disease: a case report.

We present the case of a male patient with a family history of both bipolar disorder (BD) and Wilson's disease (WD). Wilson's disease was diagnosed for this patient in 2008, at the age of 28 years, and shortly thereafter his bipolar illness began with depressive episodes. The patient has been treated with zinc sulphate for WD and with antidepressants for depression. In 2009, lithium was added, and in 2010 antidepressants were discontinued. During treatment with zinc sulphate, a gradual improvement of hepatic indices and a decrease of mandibulofacial dystonia was noted. In 2011, a hypomanic state occurred which subsided with an increase of the lithium dose. Since then, the patient has been mostly in a euthymic mood with subclinical hypomanic periods. We suggest that lithium may be a viable option for treating bipolar illness in patients with Wilson's disease.

Vitamin B12 level may be related to the efficacy of single ketamine infusion in bipolar depression.

The single infusion of ketamine, an N-methyl-d-aspartic acid (NMDA) glutamate receptor antagonist, exerts a therapeutic effect in both unipolar and bipolar depression. Homocysteine (HCY) acts agonistically on the NMDA receptor, hyperhomocysteinemia is related to depression, and folic acid and vitamin B12 are associated with HCY system. We estimated the serum levels of these substances in 20 bipolar depressed patients before ketamine infusion. 10 patients responded favorably to this procedure, as their score on the Hamilton depression rating scale, compared to baseline, was reduced by more than 50%, after 7 days. The vitamin B12 level was significantly higher in "responders" compared to the remaining patients. No differences between the 2 groups were found with regard to HCY, folic acid levels and such clinical factors as age, duration of illness and duration of current episode. These preliminary data suggest that the vitamin B12 level may be connected with the efficacy of ketamine infusion in bipolar depression.

Applicability of 2,4-dinitrophenylhydrazine (DNPH) method of protein oxidative damage measurement in the seminal plasma of canine ( Canis lupus familiaris) and stallion ( Equus caballus).

Seminal plasma (SP) proteins are responsible for sperm functional quality. Developing a reliable method to determine the degree of oxidative damage of these proteins is important for establishing semen fertilizing ability. The main aim of the study was to verify the applicability of protein carbonyl derivatives measurement in the SP of canine and stallion, using a method with 2,4-dinitrophenylhydrazine (DNPH). The research material consisted of ejaculates obtained from eight English Springer Spaniels, and from seven half-blood stallions during the breeding and non-breeding season. The content of carbonyl groups in the SP was measured on the basis of the reactions with DNPH. The following reagent variants were used to dissolve protein precipitates: Variant 1 (V1) - 6M Guanidine solution and Variant 2 (V2) - 0.1M NaOH solution. It has been shown that to obtain reliable results for the measurement of protein carbonylated groups in the dog and horse SP, both 6M Guanidine and 0.1M NaOH may be used. A correlation was also found between the number of carbonyl groups and the total protein content in the canine (V1: r = -0.724; V2: r = -0.847) and stallion (V1: r = -0.336; V2: r = -0.334) SP. Additionally, the study showed a higher content (p≤0.05) of protein carbonyl groups in the stallion SP in the non-breeding season compared to the breeding season. The method based on the reaction with DNPH, due to its simplicity and cost effectiveness, appears to be suitable for large-scale application in the determination of the SP proteins oxidative damage in dog and horse semen.

Ultrastructural aspects of acute pancreatitis induced by 2, 2'-azobis (2-amidinopropane) dihydrochloride (AAPH) in rats.

Pathophysiology of acute pancreatitis (AP) has not been clearly established; nevertheless, accumulating evidence implicates highly reactive oxygen species (ROS) as important mediators of exocrine tissue damage. In this study, we used a water-soluble radical initiator, 2,2 -azobis-(2-amidinopropane) dihydrochloride (AAPH), to investigate the consequences of oxidative stress insult to the rat pancreas. The detailed characterisation of acini ultrastructural changes in the early course (3, 6, 12, 24 h) of AAPH-induced pancreatitis (40 mg/1 kg body weight) was performed. Considerable damage to the mitochondria in acinar cells manifested by increased translucence of the matrix, partial destruction of cristae, and formation of myelin figures were noted. At the same time, focal dilation, degranulation of rough endoplasmic reticulum, and reduced number of zymogen granules was observed. The most prominent ultrastructural feature was accumulation of highly polymorphic cytoplasmic vacuoles in acinar cells. Double membrane-bound autophagosomes, different in size and shape, with sequestered organelles, autophagolysosomes, and large, empty, single-membrane-bound vacuoles were observed within the cytoplasm. The results indicate that intensive and impaired autophagy mediates pathological accumulation of vacuoles in acinar cells. The rat model of acute pancreatitis induced by AAPH is useful to investigate the early events of oxidative stress insult to the pancreas.

Pelvic floor disorders: role of new ultrasonographic techniques.

The paper presents the role of various ultrasound modalities in the diagnostics of female pelvic floor disorders (PFD). It describes the use of two/three/four-dimensional transperineal ultrasound and endocavitary transducers, which, up to now, have been used for proctological examinations and prostate cancer brachytherapy. Ultrasonography is the most widely available imaging modality. As a result of technical progress, novel transducers and more sophisticated software have recently been introduced to the market providing more information about the anatomy of pelvic organs. Some features of these transducers, such as higher frequency and multiplanar imaging, enable better visualisation of pelvic floor organs. In-depth knowledge of the technical and physical properties of modern ultrasonography, as well as its advantages and limitations, could provide an integrated approach to imaging of PFD. Technical modalities, the wide availability of ultrasonographic techniques, and an understanding of the imaging possible with modern ultrasonography could improve our understanding of PFD and allow better assessment in pre- and post-surgical management.

Herpes simplex virus type 1 DNA is located within Alzheimer's disease amyloid plaques.

The brains of Alzheimer's disease sufferers are characterized by amyloid plaques and neurofibrillary tangles. However, the cause(s) of these features and those of the disease are unknown, in sporadic cases. We previously showed that herpes simplex virus type 1 is a strong risk factor for Alzheimer's disease when in the brains of possessors of the type 4 allele of the apolipoprotein E gene (APOE-epsilon4), and that beta-amyloid, the main component of plaques, accumulates in herpes simplex virus type 1-infected cell cultures and mouse brain. The present study aimed to elucidate the relationship of the virus to plaques by determining their proximity in human brain sections. We used in situ polymerase chain reaction to detect herpes simplex virus type 1 DNA, and immunohistochemistry or thioflavin S staining to detect amyloid plaques. We discovered a striking localization of herpes simplex virus type 1 DNA within plaques: in Alzheimer's disease brains, 90% of the plaques contained the viral DNA and 72% of the DNA was associated with plaques; in aged normal brains, which contain amyloid plaques at a lower frequency, 80% of plaques contained herpes simplex virus type 1 DNA but only 24% of the viral DNA was plaque-associated (p < 0.001). We suggest that this is because in aged normal individuals, there is a lesser production and/or greater removal of beta-amyloid (Abeta), so that less of the viral DNA is seen to be associated with Abeta in the brain. Our present data, together with our finding of Abeta accumulation in herpes simplex virus type 1-infected cells and mouse brain, suggest that this virus is a major cause of amyloid plaques and hence probably a significant aetiological factor in Alzheimer's disease. They point to the usage of antiviral agents to treat the disease and possibly of vaccination to prevent it.

Clinical significance of activin A and myostatin in patients with pancreatic adenocarcinoma and progressive weight loss.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by progressive weight loss and nutritional deterioration. Several cytokines, such as activin A and myostatin, ligands of the transforming growth factor-ß superfamily, have been shown to influence the pathogenesis of muscle wasting and tumor progression. The aim of our study was to assess the clinical significance of these cytokines in patients with different stages of PDAC. The study included 93 patients: 73 with newly diagnosed PDAC and 20 healthy volunteers as the control group. PDAC patients included 42 diagnosed with non-metastatic pancreatic cancer (stage I - III) and 31 patients with metastatic cancer (stage IV). The peripheral venous blood samples were collected from each patients at the time of cancer diagnosis and plasma concentrations of activin A and myostatin have been measured with an enzyme-linked immunoassay. Forty five patients (61.6%) presented weight loss > 5%, including 24 (57.1%) with stage I - II and 21 (67.7%) with metastatic PDAC (P > 0.05). Plasma levels of activing A were significantly higher in metastatic PDAC patients compared with stage I - III PDAC patients and control group (P < 0.01). The relationship between higher activin A levels and weight loss was also observed (P < 0.05). On the other hand, myostatin was not associated with weight loss in analysed group of patients. In conclusion, the current study demonstrates that high activin A plasma levels at the time of PDAC diagnosis is associated with unintentional weight loss and may be an useful biomarker for identifying patients with metastatic disease. However, further prospective studies are needed to fully explore the clinical significance of myostatin in pathogenesis of progressive weight loss in PDAC patients.

Psoralen plus ultraviolet A +/- interferon-alpha treatment resistance in mycosis fungoides: the role of tumour microenvironment, nuclear transcription factor-kappaB and T-cell receptor pathways.

BACKGROUND: Interferon (IFN)-alpha is widely used in the treatment of mycosis fungoides (MF) and when used in combination with photochemotherapy (psoralen plus ultraviolet A, PUVA) both improved response and duration of complete remission have been reported. However, in spite of encouraging results of the initial studies, currently there is no information available on specific prognostic factors enabling prediction of patients' resistance to PUVA +/- IFN-alpha treatment. OBJECTIVES: To identify factors responsible for resistance to PUVA +/- IFN-alpha treatment in MF patients. PATIENTS/METHODS: The gene expression profiling of pretreatment samples from 29 patients diagnosed as IA, IB or IIA stage of MF enrolled in a randomized PUVA vs. PUVA + IFN-alpha clinical trial was analysed using cDNA microarrays. A Cox model (SAM) and gene set enrichment analysis (GSEA) were used for identification of genes and biologically significant pathways related to resistance to treatment. RESULTS: Genes involved in NF-kappaB signalling, T-cell receptor (TCR) signalling, cytokine signalling and proliferation were differentially expressed between responders and nonresponders. Interestingly, expression of markers representative of those pathways was found not only in the tumoral cells, but also in specific subpopulations of macrophages, dendritic cells and other non-neoplastic cell types constituting the tumour microenvironment, likely involved in the promotion of survival and proliferation of cutaneous T-cell lymphoma. CONCLUSIONS: Gene expression changes in both the tumour and the tumour microenvironment are an important determinant of treatment outcome in early-stage MF patients. Some proinflammatory factors such as NF-kappaB, inflammatory cytokines and their receptors in addition to TCR-associated molecules could be promising targets for MF treatment.

Ultrastructural response of arcuate nucleus neurons to fasting in aged rats.

The arcuate nucleus of the hypothalamus (ARH) is involved in the control of energy homeostasis. Leptin - an adipocyte derived hormone - is known to act on the hypothalamic nuclei and thus to control body weight by food intake reduction. Oxidative stress is believed to be implicated in leptin signalling. However, its relevance for leptin-induced signal transduction within ARH remains unclear. The goal of the study was to investigate the effect of fasting on morphological alterations of the neuronal endoplasmic reticulum/Golgi network as well as on the expression of leptin receptors in the arcuate nucleus of aged rats. Male Wistar rats, aged 24 months, were fasted for 96 hours. The control animals were fed ad libitum. Membranous whorls in the ARH neurons were visualized using the electron microscopy technique. Leptin receptors in the membranes of ARH neurons were determined immunohistochemically (IHC), and soluble leptin receptors in the plasma as well as plasma isoprostanes were quantified immunochemically (ELISA). An intense formation of membranous whorls was observed, directly associated with the cisternae of the rough endoplasmic reticulum, as well as lamellar bodies. Interestingly, the whorls were often localized near a well-developed Golgi complex. Moreover, some Golgi complexes displayed an early stage of whorl formation. Groups of residual lipofuscin granules were found in the immediate proximity of the whorls. An increased immunoreactivity with neuronal leptin receptors suggests that hypersensitive neurons may still effectively respond to the fasting serum levels of leptin, mediating ultrastructural transformation of ARH neurons during short-term fasting. Having observed a significant accumulation of lipofuscin granules and a marked increase of total 8-isoprostane serum level in the fasting rats, we hypothesize that signal transduction within the neurons of ARH is dependent on oxidative stress phenomena.

Controlled cholesterol efflux from the aortic smooth muscle cells triggers microheterogeneity of plasma membrane lipids and induces modification of the mitochondrial topology.

It is generally accepted that phospholipids of plasma membrane display lateral segregation into small microdomains commonly known as lipid rafts. Such lateral lipid organization is under the control of cholesterol. Cholesterol depletion evolved by methyl-beta-cyclodextrin (MCD) has been found to induce further marked perturbation in lateral lipid organization, evidenced in the high field part of electron paramagnetic resonance spectra of plasma membranes labelled with a spectroscopic probe, namely 5-doxyl-stearic acid (5DOXS). Such perturbation of surface lipid topo-logy has been found to induce distinct changes in the mitochondrial morpho-logy, i.e. switch from filamentous form into small granular form.

NADH-generating substrates reduce peroxyl radical toxicity in RL-34 cells.

There is general agreement that oxidative stress may induce apoptotic and necrotic cell death. Recently it has been shown that NADH can be considered an important antioxidant as it reacts with peroxyl and alkoxyl radicals under in vitro conditions. Therefore, in the present study we hypothesized that an increase in intracellular NADH using specific substrates will protect RL-34 cells against cytotoxicity of 2'-azobis (2-amidinopropane) dihydrochloride (AAPH), which is a peroxyl radical generating compound. Cells treated for 24 hours with 6.0 mM AAPH were severely damaged: mitochondria were vacuolated, and the level of free radicals significantly increased. Both apoptotic and necrotic cells were detected (11.1% and 11.4%, respectively) even after 5 hours of treatment. Pretreatment of the cells with substrates which increase the intracellular level of NADH, such as lactate, beta-hydroxybutyrate, and ethanol, distinctly inhibited AAPH-induced reactive oxygen species (ROS) formation and cell death. On the other hand, acetoacetate (AcA), which decrease the intracellular level of NADH, had opposite effects. Interestingly, NADH-generating substrates augment, while AcA reduced superoxide radical formation induced by AAPH. These results may suggest that although NADH generating substrates may exert some deleterious effects within a cell by inducing reductive stress, they diminish alkoxyl or peroxyl radical cytotoxicity. The protection is associated with a decrease in ROS formation measured by dichlorofluorescein, but with an increase in superoxide radical formation.