The role of environmental sensitivity in the mental health of Syrian refugee children: a multi-level analysis.

Individuals with high environmental sensitivity have nervous systems that are disproportionately receptive to both the protective and imperilling aspects of the environment, suggesting their mental health is strongly context-dependent. However, there have been few consolidated attempts to examine putative markers of sensitivity, across different levels of analysis, within a single cohort of individuals with high-priority mental health needs. Here, we examine psychological (self-report), physiological (hair hormones) and genetic (polygenic scores) markers of sensitivity in a large cohort of 1591 Syrian refugee children across two waves of data. Child-caregiver dyads were recruited from informal tented settlements in Lebanon, and completed a battery of psychological instruments at baseline and follow-up (12 months apart). Univariate and multivariate Bayesian linear mixed models were used to examine a) the interrelationships between markers of sensitivity and b) the ability of sensitivity markers to predict anxiety, depression, post-traumatic stress disorder, and externalising behaviour. Self-reported sensitivity (using the Highly Sensitive Child Scale) significantly predicted a higher burden of all forms of mental illness across both waves, however, there were no significant cross-lagged pathways. Physiological and genetic markers were not stably predictive of self-reported sensitivity, and failed to similarly predict mental health outcomes. The measurement of environmental sensitivity may have significant implications for identifying and treating mental illness, especially amongst vulnerable populations, but clinical utility is currently limited to self-report assessment.

Pharmacogenomics in Pediatric Oncology: Mitigating Adverse Drug Reactions While Preserving Efficacy.

Cancer is the leading cause of death in American children older than 1 year of age. Major developments in drugs such as thiopurines and optimization in clinical trial protocols for treating cancer in children have led to a remarkable improvement in survival, from approximately 30% in the 1960s to more than 80% today. Short-term and long-term adverse effects of chemotherapy still affect most survivors of childhood cancer. Pharmacogenetics plays a major role in predicting the safety of cancer chemotherapy and, in the future, its effectiveness. Treatment failure in childhood cancer-due to either serious adverse effects that limit therapy or the failure of conventional dosing to induce remission-warrants development of new strategies for treatment. Here, we summarize the current knowledge of the pharmacogenomics of cancer drug treatment in children and of statistically and clinically relevant drug-gene associations and the mechanistic understandings that underscore their therapeutic value in the treatment of childhood cancer.

War exposure, post-traumatic stress symptoms and hair cortisol concentrations in Syrian refugee children.

Altered secretion of cortisol, the primary effector of the hypothalamus-pituitary-adrenal axis, has been proposed as a means by which traumatic experiences compromise later mental health. However, despite the popularity of cortisol as a potential biomarker for stress and adversity, findings are inconsistent, and little is known about the impact of war-related trauma on stress physiology of children and adolescents. Here we aimed to evaluate the relationships between war exposure, current living conditions, hair cortisol concentrations (HCC) and post-traumatic stress disorder (PTSD) symptoms in a large cohort of Syrian refugee children and adolescents (6-18 years) and their caregiver. This longitudinal observational study assessed Syrian refugee children and adolescents in two waves, 1 year apart, within informal tented settlements in Lebanon. The relationships between war exposure, time since leaving Syria, PTSD symptoms and HCC were investigated using linear mixed-model regression utilising both waves of data collected (Y1: N = 1574, Y2: N = 923). Hair cortisol concentration was positively, but weakly associated with the number of war-related events experienced. This was limited to those who were at least 12 years old at the time of war exposure. Conversely, HCC decreased with time since leaving Syria. HCC was also associated with PTSD symptoms but not with the quality of their current living conditions. This study revealed that changes to hypothalamic-pituitary-adrenal axis activity may accompany both earlier war exposure and current PTSD symptoms in children and adolescents. Additionally, early adolescence may be a particularly sensitive time in terms of trauma-related changes to the hypothalamic-pituitary-adrenal axis.

Relationships among Cortisol, Perceived Stress, and Dental Caries Experience in Adolescents and Young Adults.

INTRODUCTION: Stress can impact mental and physical health, especially during adolescence and young adulthood, but the extent of its contribution to dental caries is poorly understood. The present study assessed the association between perceived stress, cortisol levels (in hair and saliva), and overall caries experience of adolescents and young adults aged 15-25 years. METHODS: Hair and saliva samples were obtained from 93 participants free of periodontal disease. Cortisol in hair and saliva was determined using a competitive enzyme-linked immunosorbent assay. Participants completed a perceived stress questionnaire and underwent full-mouth oral examination by a calibrated examiner. Dental caries experience was based on the decayed, missing, and filled teeth (DMFT) index. Sociodemographic variables were also recorded. RESULTS: There were significantly higher hair cortisol levels and perceived stress scale (PSS) scores in individuals with dental caries experience (DMFT≥1) than in those without (DMFT = 0). However, there was no significant difference in salivary cortisol concentration. A binary logistic regression revealed that higher hair cortisol levels and greater scores on the perceived stress scale were associated with increased odds of having experienced dental caries. In contrast, no significant association was found between salivary cortisol concentration and dental caries. Using multivariable regression models, caries experience was found to be significantly associated with both hair cortisol levels and PSS scores. These associations remained statistically significant even after adjusting for sociodemographic variables. CONCLUSION: Hair cortisol levels and perceived stress have a significant association with dental caries experience, whereas salivary cortisol concentrations do not.

Medical cannabis for children: Evidence and recommendations.

Interest in using cannabis products for a medical purpose in children under the age of 18 years is increasing. There are many medical cannabis products available that can include cannabidiol (CBD) or delta-9-tetrahydrocannabinol (THC), or both. Despite many therapeutic claims, there are few rigorous studies to inform the dosing, safety, and efficacy of medical cannabis in paediatric clinical practice. This statement reviews the current evidence and provides recommendations for using medical cannabis in children. Longer-term (2-year) reports support the sustained tolerability and efficacy of cannabidiol therapy for patients with Lennox-Gastaut and Dravet syndromes. CBD-enriched cannabis extracts containing small amounts of THC have been evaluated in a small number of paediatric patients, and further research is needed to inform clinical practice guidelines. Given the widespread use of medical cannabis in Canada, paediatricians should be prepared to engage in open, ongoing discussions with families about its potential benefits and risks, and develop individualized plans that monitor efficacy, reduce harms, and mitigate drug-drug interactions.

Les données probantes et les recommandations sur le cannabis à des fins médicales chez les enfants.

L'intérêt envers l'utilisation des produits du cannabis à des fins médicales chez les enfants de moins de 18 ans augmente. De nombreux produits du cannabis à des fins médicales contiennent du cannabidiol, du delta-9-tétrahydrocannabinol ou ces deux produits. Malgré les nombreuses prétentions thérapeutiques, peu d'études rigoureuses guident la posologie, l'innocuité et l'efficacité du cannabis à des fins médicales en pédiatrie clinique. Le présent document de principes passe en revue les données probantes à jour et expose les recommandations sur l'utilisation du cannabis à des fins médicales chez les enfants. Les rapports à plus long terme (deux ans) souscrivent à la tolérabilité et à l'efficacité soutenues d'un traitement au cannabidiol chez les patients ayant le syndrome de Lennox-Gastaut ou le syndrome de Dravet. Les extraits de cannabis enrichis de cannabidiol qui renferment de petites quantités de delta-9-tétrahydrocannabinol ont été évalués auprès d'un petit nombre de patients d'âge pédiatrique, et d'autres recherches devront être réalisées pour éclairer les guides de pratique clinique. Étant donné l'utilisation répandue du cannabis à des fins médicales au Canada, les pédiatres devraient être prêts à participer à des échanges ouverts et continus avec les familles au sujet de ses avantages potentiels et de ses risques, ainsi qu'à préparer des plans individuels en vue d'en surveiller l'efficacité, de réduire les méfaits et de limiter les interactions médicamenteuses.

Removing barriers to accessing medical cannabis for paediatric patients.

Medical cannabis (MC) may offer therapeutic benefits for children with complex neurological conditions and chronic diseases. In Canada, parents, and caregivers frequently report encountering barriers when accessing MC for their children. These include negative preconceived notions about risks and benefits, challenges connecting with a knowledgeable healthcare provider (HCP), the high cost of MC products, and navigating MC product shortages. In this manuscript, we explore several of these barriers and provide recommendations to decision-makers to enable a family-centered and evidence-based approach to MC medicine and research for children.

Metabolomic identification of predictive and early biomarkers of cisplatin-induced acute kidney injury in adult head and neck cancer patients.

AIM: Cisplatin causes acute kidney injury (AKI) in approximately one third of patients. Serum creatinine and urinary output are poor markers of cisplatin-induced AKI. Metabolomics was utilized to identify predictive or early diagnostic biomarkers of cisplatin-induced AKI. METHODS: Thirty-one adult head and neck cancer patients receiving cisplatin (dose ≥70 mg/m2 ) were recruited for metabolomics analysis. Urine and serum samples were collected prior to cisplatin (pre), 24-48 h after cisplatin (24-48 h) and 5-14 days (post) after cisplatin. Based on serum creatinine concentrations measured at the post timepoint, 11/31 patients were classified with clinical AKI. Untargeted metabolomics was performed using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Metabolic discrimination was observed between "AKI" patients and "no AKI" patients at all timepoints. Urinary glycine, hippuric acid sulfate, 3-hydroxydecanedioc acid and suberate were significantly different between AKI patients and no AKI patients prior to cisplatin infusion. Urinary glycine and hippuric acid sulfate were lower (-2.22-fold and -8.85-fold), whereas 3-hydroxydecanedioc acid and suberate were higher (3.62-fold and 1.91-fold) in AKI patients relative to no AKI patients. Several urine and serum metabolites were found to be altered 24-48 h following cisplatin infusion, particularly metabolites involved with mitochondrial energetics. CONCLUSIONS: We propose glycine, hippuric acid sulfate, 3-hydroxydecanedioc acid and suberate as predictive biomarkers of predisposition to cisplatin-induced AKI. Metabolites indicative of mitochondrial dysfunction may serve as early markers of subclinical AKI.

Risk and resilience in Syrian refugee children: A multisystem analysis.

Refugee children are often exposed to substantial trauma, placing them at increased risk for mental illness. However, this risk can be mitigated by a capacity for resilience, conferred from multiple ecological systems (e.g., family, community), including at an individual biological level. We examined the ability of hair cortisol concentrations and polygenic scores for mental health to predict risk and resilience in a sample of Syrian refugee children (n = 1359). Children were categorized as either at-risk or resilient depending on clinical thresholds for posttraumatic stress disorder, depression, and externalizing behavior problems. Logistic regression was used to examine main and interacting effects while controlling for covariates. Elevated hair cortisol concentrations were significantly associated with reduced resilience (odds ratio (OR)=0.58, 95%CI [0.40, 0.83]) while controlling for levels of war exposure. Polygenic scores for depression, self-harm, and neuroticism were not found to have any significant main effects. However, a significant interaction emerged between hair cortisol and polygenic scores for depression (OR=0.04, 95%CI [0.003 0.47]), suggesting that children predisposed to depression were more at risk for mental health problems when hair cortisol concentrations were high. Our results suggest that biomarkers (separately and in combination) might support early identification of refugee children at risk for mental health problems.

Pathophysiology of drug hypersensitivity.

Drug hypersensitivity reactions (DHRs) are type B adverse drug reactions (ADRs) traditionally defined as unpredictable, dose independent and not related to the drug pharmacology. DHRs, also called drug allergy if the immune system involvement is confirmed, represent around one-sixth of all ADRs and can cause major clinical problems due to their vague clinical presentation and irregular time course. Understanding the underlying pathophysiology of DHRs is very important for their diagnosis and management. Multiple layers of evidence exist pointing to the involvement of the immune system in DHRs. Recent data have led to a paradigm shift in our understanding of the exact pathophysiology of these reactions. Numerous hypotheses proposing explanation on how a low molecular weight drug molecule can elicit an immune reaction have been proposed. In addition to the classical "hapten" hypothesis, the reactive metabolite hypothesis, the pharmacological interaction with the immune system (p-i) concept, the danger/injury hypothesis and the altered peptide repertoire hypothesis have been proposed. We here introduce the inflammasome activation hypothesis and the cross-reactivity hypothesis as additional models explaining the pathophysiology of DHRs. Available data supporting these hypotheses are briefly summarized and discussed. We also introduced the cross-reactivity model, which may provide a platform to appreciate the potential role played by other factors leading to the activation of the immune system. We believe that although the drug in question could be the trigger of the reaction, the components of the immune system mediating the reaction do not act in isolation but rather are affected by the proinflammatory milieu occurring at the time of the reaction. This review attempts to summarize the available evidence to further illustrate the pathophysiology of DHRs.

Drug reaction with eosinophilia and systemic symptoms (DRESS): A tertiary care centre retrospective study.

AIMS: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, drug-induced severe adverse reaction that usually occurs 3-6 weeks after initial exposure to certain drugs. It affects mainly adults and children to a lesser extent. Clinical features include fever, facial oedema, generalized skin rash, lymphadenopathy, haematological abnormalities and internal organ involvement. The objective was to investigate the clinical and laboratory features of patients with DRESS in our centre. METHODS: We retrospectively describe and analyse 19 cases of DRESS whose diagnosis was based on the RegiSCAR criteria (≥6 points) that occurred from January 2009 to December 2019. RESULTS: Patient age ranged from 4 to 76 years (4 children/15 adults); 10 were female (52.3%). The most common culprit drugs were antibiotics (74%) and anticonvulsants (21%). The most common comorbidities were epilepsy (26%) and hypertension (26%). All patients developed cutaneous manifestations and of those, 58% presented facial oedema. Liver function tests, urea/creatinine and troponin elevation were present in 74, 32 and 42%, respectively. The median time to develop the skin rash after the drug exposure was 3.7 weeks (interquartile range 2.4-4.2 wk). Eosinophilia (≥0.7 × 109 /L) was present in 95% of the patients and peaked around 10 days after the skin manifestations. Leucocytosis and reactive lymphocytes were reported in 84% and 26% of all patients respectively. Treatment with systemic steroids was reported in 16 patients. The mean recovery time was 2 weeks (interquartile range 2-3.5 wk) and mortality was 5%. CONCLUSION: DRESS is a serious condition with significant morbidity and mortality, which requires more research for a better understanding.

Pharmacogenomic testing in paediatrics: Clinical implementation strategies.

Pharmacogenomics (PGx) relates to the study of genetic factors determining variability in drug response. Implementing PGx testing in paediatric patients can enhance drug safety, helping to improve drug efficacy or reduce the risk of toxicity. Despite its clinical relevance, the implementation of PGx testing in paediatric practice to date has been variable and limited. As with most paediatric pharmacological studies, there are well-recognised barriers to obtaining high-quality PGx evidence, particularly when patient numbers may be small, and off-label or unlicensed prescribing remains widespread. Furthermore, trials enrolling small numbers of children can rarely, in isolation, provide sufficient PGx evidence to change clinical practice, so extrapolation from larger PGx studies in adult patients, where scientifically sound, is essential. This review paper discusses the relevance of PGx to paediatrics and considers implementation strategies from a child health perspective. Examples are provided from Canada, the Netherlands and the UK, with consideration of the different healthcare systems and their distinct approaches to implementation, followed by future recommendations based on these cumulative experiences. Improving the evidence base demonstrating the clinical utility and cost-effectiveness of paediatric PGx testing will be critical to drive implementation forwards. International, interdisciplinary collaborations will enhance paediatric data collation, interpretation and evidence curation, while also supporting dedicated paediatric PGx educational initiatives. PGx consortia and paediatric clinical research networks will continue to play a central role in the streamlined development of effective PGx implementation strategies to help optimise paediatric pharmacotherapy.

Recommendations for procedural sedation in infants, children, and adolescents.

Many paediatric patients require sedation and analgesia for diagnostic testing and therapeutic procedures outside the operating room. This statement reviews the literature on procedural sedation, focusing on the prevention of adverse events through the selection of appropriate patients, advance preparation for emergency situations, and adequate monitoring during and after the administration of pharmacologic agents. Procedural sedation should only be performed by clinicians who are competent in airway management and resuscitation, as part of a hospital program with active and engaged quality assurance and safety initiatives. Recommendations include the development of institutional policies and procedures for the safe delivery of procedural sedation in infants, children, and adolescents.

The use of oral opioids to control children's pain in the post-codeine era.

Pain is a common problem for children, and pain management comprises both pharmacologic and nonpharmacologic measures. For moderate to severe pain, oral opioids have been a popular choice for the last few decades. Codeine has historically been the best-known oral opioid for use in children. However, availability and use of codeine have sharply declined due to safety concerns. A variety of other opioids have been used in place of codeine, but data are limited regarding their efficacy and safety in children. While the same pathways metabolize oral oxycodone as codeine, oxycodone's pharmacokinetics varies widely. There are also limited data on the safety and efficacy of oral hydromorphone and tramadol use for children. Oral morphine is the opiate alternative to codeine for which there is the most evidence of safety and efficacy in children. Research is needed to investigate both other opioids and non-opioid approaches to guide evidence-based analgesic therapy and treatment for moderate-to-severe pain in children.

Recommandations sur la sédation lors d'une intervention diagnostique ou thérapeutique chez les nourrissons, les enfants et les adolescents.

De nombreux patients pédiatriques ont besoin de sédation et d'analgésie lors de tests diagnostiques et d'actes thérapeutiques hors de la salle d'opération. Le présent document de principes contient une analyse bibliographique de la sédation interventionnelle (qu'on appelle aussi sédation procédurale), axée sur la prévention des événements indésirables grâce à la sélection des patients appropriés, à la préparation aux situations d'urgence et à la surveillance nécessaire pendant et après l'administration des agents pharmacologiques. Seuls des cliniciens formés en assistance respiratoire et en réanimation devraient être autorisés à l'effectuer, dans le cadre d'un programme hospitalier comportant des initiatives à la fois dynamiques et soutenues en matière de sécurité et d'assurance de la qualité. La rédaction de politiques et de protocoles sur la sédation interventionnelle sécuritaire chez les nourrissons, les enfants et les adolescents fait partie des recommandations.

Les opioïdes par voie orale en remplacement de la codéine pour contrôler la douleur chez les enfants.

La douleur est un problème courant chez les enfants. Des mesures pharmacologiques et non pharmacologiques sont utilisées pour la prendre en charge. Depuis quelques décennies, les opioïdes par voie orale sont populaires pour soulager la douleur modérée à grave. La codéine a longtemps été l'opioïde par voie orale le plus connu pour les enfants. Pour des raisons de sécurité, elle est désormais nettement moins accessible et moins employée. Divers autres opioïdes la remplacent, mais les données sur leur efficacité et leur sécurité sont limitées chez les enfants. L'oxycodone par voie orale emprunte les mêmes voies métaboliques que la codéine, mais sa pharmacocinétique est très variable. Les données sur la sécurité et l'efficacité de l'hydromorphone et du tramadol par voie orale chez les enfants sont également limitées. Lorsqu'on y recourt au lieu de la codéine, la morphine par voie orale est l'opiacé dont la sécurité et l'efficacité sont les mieux démontrées chez les enfants. Des recherches devront être réalisées pour explorer d'autres approches relatives aux médicaments opioïdes et non opioïdes, afin d'orienter les traitements analgésiques fondés sur des données probantes qui soulageront la douleur modérée à grave chez les enfants.

Paediatric serum sickness-like reaction: A 10-year retrospective cohort study.

BACKGROUND: Serum sickness-like reaction (SSLR) is an acute inflammatory condition affecting predominantly children. The pathophysiology remains unclear, but drugs are considered the main trigger. OBJECTIVE: The aim of this study was to describe the clinical and laboratory features, triggers, and treatment modalities in children diagnosed with SSLR. METHODS: We conducted a 10-year retrospective cohort study including all paediatric patients (0 to 18 years old) with query SSLR referred to the Adverse Drug Reactions Clinic at the Children's Hospital of Western Ontario. Diagnostic criteria included acute skin rash plus joint inflammation with or without fever. RESULTS: We included 83 patients (47 females). Age ranged from 11 months to 12 years (mean 3.2 years). Amoxicillin was the trigger in 82.7% of patients. The mean time between the exposure to the triggering drug and the development of the symptoms was 8.5 days. Urticaria-like and Erythema multiforme-like lesions were present in 35% and 38.5% of the cases, respectively. Joint inflammation affecting hands/feet was present in 60%. Pruritus, lip/eye swelling, and fever were reported in 33, 31, and 45% of patients, respectively. The lymphocyte toxicity assay (LTA) showed incremental T-cell toxicity in 32 of 34 patients. Children that received treatment with antihistamines/nonsteroidal anti-inflammatory drugs (NSAIDs) plus oral steroids had a mean recovery time shorter than those treated only with antihistamines/NSAIDs (6 versus 8 days; P=0.09). CONCLUSIONS: In our study, SSLR was mostly triggered by amoxicillin and had a mean time presentation of 8.5 days. Further prospective and well-conducted studies are needed.

Dietary intake of sodium by children: Why it matters.

Dietary sodium is required in very small amounts to support circulating blood volume and blood pressure (BP). Available nutritional surveillance data suggest that most Canadian children consume sodium in excess of their dietary requirements. Approximately 80% of the sodium Canadians consume comes from processed and packaged foods. High sodium intakes in children may be an indicator of poor diet quality. Results from systematic reviews and meta-analyses have demonstrated that decreasing dietary sodium in children leads to small but clinically insignificant decreases in BP. However, population-level strategies to reduce sodium consumption, such as food product reformulation, modifying food procurement processes, and federal healthy eating policies, are important public health initiatives that can produce meaningful reductions in sodium consumption and help to prevent chronic disease in adulthood.

Beta-lactam allergy in the paediatric population.

Beta-lactam allergy is commonly diagnosed in paediatric patients, but over 90% of individuals reporting this allergy are able to tolerate the medications prescribed after evaluation by an allergist. Beta-lactam allergy labels are associated with negative clinical and administrative outcomes, including use of less desirable alternative antibiotics, longer hospitalizations, increasing antibiotic-resistant infections, and greater medical costs. Also, children with true IgE-mediated allergy to penicillin medications are often advised to avoid all beta-lactam antibiotics, including cephalosporins, which is likely unnecessary in greater than 97% of those reporting penicillin allergies. Most patients can be safely treated with penicillin or amoxicillin if they do not have a history compatible with IgE-mediated or systemic, delayed reactions such as Stevens-Johnson syndrome (SJS), serum sickness-like reactions, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, or acute generalized exanthematous pustulosis (AGEP). Guidance is provided on how to stratify risk of beta-lactam allergy, and on test dosing and monitoring in the outpatient setting for patients deemed low risk. Guidance for patients at higher risk of beta-lactam allergy includes criteria for appropriate referral to allergists and the use of alternative antimicrobials, such as cephalosporins, while awaiting specialist assessment.

HIV-1 tat expression and sulphamethoxazole hydroxylamine mediated oxidative stress alter the disulfide proteome in Jurkat T cells.

BACKGROUND: Adverse drug reactions (ADRs) are a significant problem for HIV patients, with the risk of developing ADRs increasing as the infection progresses to AIDS. However, the pathophysiology underlying ADRs remains unknown. Sulphamethoxazole (SMX) via its active metabolite SMX-hydroxlyamine, when used prophylactically for pneumocystis pneumonia in HIV-positive individuals, is responsible for a high incidence of ADRs. We previously demonstrated that the HIV infection and, more specifically, that the HIV-1 Tat protein can exacerbate SMX-HA-mediated ADRs. In the current study, Jurkat T cell lines expressing Tat and its deletion mutants were used to determine the effect of Tat on the thiol proteome in the presence and absence of SMX-HA revealing drug-dependent changes in the disulfide proteome in HIV infected cells. Protein lysates from HIV infected Jurkat T cells and Jurkat T cells stably transfected with HIV Tat and Tat deletion mutants were subjected to quantitative slot blot analysis, western blot analysis and redox 2 dimensional (2D) gel electrophoresis to analyze the effects of SMX-HA on the thiol proteome. RESULTS: Redox 2D gel electrophoresis demonstrated that untreated, Tat-expressing cells contain a number of proteins with oxidized thiols. The most prominent of these protein thiols was identified as peroxiredoxin. The untreated, Tat-expressing cell lines had lower levels of peroxiredoxin compared to the parental Jurkat E6.1 T cell line. Conversely, incubation with SMX-HA led to a 2- to 3-fold increase in thiol protein oxidation as well as a significant reduction in the level of peroxiredoxin in all the cell lines, particularly in the Tat-expressing cell lines. CONCLUSION: SMX-HA is an oxidant capable of inducing the oxidation of reactive protein cysteine thiols, the majority of which formed intermolecular protein bonds. The HIV Tat-expressing cell lines showed greater levels of oxidative stress than the Jurkat E6.1 cell line when treated with SMX-HA. Therefore, the combination of HIV Tat and SMX-HA appears to alter the activity of cellular proteins required for redox homeostasis and thereby accentuate the cytopathic effects associated with HIV infection of T cells that sets the stage for the initiation of an ADR.