Diazepam diminishes temozolomide efficacy in the treatment of U87 glioblastoma cell line.

AIMS: Many patients with glioblastoma (GBM) suffer from comorbid neurological/psychiatric disorders and, therefore, are treated with psychopharmacological agents. Diazepam (DIA) is widely adopted to treat status epilepticus, alleviate anxiety, and inhibit chemotherapy-associated delayed emesis in GBM patients. Even though temozolomide (TMZ) and DIA could be found as possible combination therapy in clinical practice, there are no reports of their combined effects in GBM. Hence, it may be of interest to investigate whether DIA enhances the antitumor efficacy of TMZ in GBM cells. METHODS: U87 human GBM was used to examine the effects of combined TMZ and DIA on cell viability, and the oxygen consumption within the cells, in order to evaluate mitochondrial bioenergetic response upon the treatment. RESULTS: The cooperative index showed the presence of antagonism between TMZ and DIA, which was confirmed on long-term observation. Moreover, the level of apoptosis after the TMZ treatment was significantly decreased when administered with DIA (p < 0.001). Concomitant use of TMZ and DIA increased the basal cell respiration rate, the oxidative phosphorylation rate, and maximal capacity of mitochondrial electron transport chain, as well as the activities of complexes I and II, vs. TMZ alone (p < 0.001). CONCLUSION: Comparing our results with data reported that DIA elicits cell cycle arrest in the G0/G1 phase and favors senescence reveals that DIA diminishes TMZ efficacy in concomitant use in the treatment of GBM. However, due to its great potency to hinder GBM proliferation and metabolism, it could be considered using DIA as maintenance therapy after TMZ cycles.

Mitochondrial energy metabolism in baby hamster kidney (BHK-21/C13) cells treated with karnozin extra® / Metabolismo energético mitocondrial en células de riñón de hámster bebé (BHK-21 / C13) tratadas con karnozin extra®

SUMMARY: Carnosine is known as a natural dipeptide, which inhibits the proliferation of tumor cells throughout its action on mitochondrial respiration and cell glycolysis. However, not much is known about its effects on the metabolism of healthy cells. We explored the effects of Karnozin EXTRA® capsule with different concentrations of L-carnosine, on the cell viability and the expressions of intermediate filament vimentin (VIM) and superoxide dismutase (SOD2) in normal fibroblasts BHK-21/C13. Furthermore, we investigated its action on the energy production of these cells. Cell viability was quantified by the MTT assay. The Clark oxygen electrode (Oxygraph, Hansatech Instruments, England) was used to measure the "intact cell respiration rate", state 3 of ADP-stimulated oxidation, maximum oxidation capacity and the activities of complexes I, II and IV. Results showed that Karnozin EXTRA® capsule in concentrations of 2 and 5 mM of L-carnosine did not induce toxic effects and morphological changes in treated cells. Our data revealed a dose-dependent immunofluorescent signal amplification of VIM and SOD2 in the BHK-21/C13 cell line. This supplement substantially increased the recorded mitochondrial respiration rates in the examined cell line. Due to the stimulation of mitochondrial energy production in normal fibroblasts, our results suggested that Karnozin EXTRA® is a potentially protective dietary supplement in the prevention of diseases with altered mitochondrial function.

RESUMEN: La carnosina se conoce como dipéptido natural, que inhibe la proliferación de células tumorales a través de su acción sobre la respiración mitocondrial y la glucólisis celular. Sin embargo, no se sabe mucho de sus efectos sobre el metabolismo de las células sanas. Exploramos los efectos de la cápsula Karnozin EXTRA® con diferentes concentraciones de L-carnosina, sobre la viabilidad celular y las expresiones de vimentina de filamento intermedio (VIM) y superóxido dismutasa (SOD2) en fibroblastos normales BHK-21 / C13. Además, estudiamos su acción sobre la producción de energía de estas células. La viabilidad celular se cuantificó mediante el ensayo MTT. Se utilizó el electrodo de oxígeno Clark (Oxygraph, Hansatech Instruments, Inglaterra) para medir la "tasa de respiración de células intactas", el estado 3 de oxidación estimulada por ADP, la capacidad máxima de oxidación y las actividades de los complejos I, II y IV. Los resultados mostraron que la cápsula de Karnozin EXTRA® en concentraciones de 2 y 5 mM de L- carnosina no indujo efectos tóxicos ni cambios morfológicos en las células tratadas. Nuestros datos revelaron una amplificación de señal inmunofluorescente dependiente de la dosis de VIM y SOD2 en la línea celular BHK-21 / C13. Este suplemento aumentó sustancialmente las tasas de respiración mitocondrial registradas en la línea celular examinada. Debido a la estimulación de la producción de energía mitocondrial en fibroblastos normales, nuestros resultados sugirieron que Karnozin EXTRA® es un suplemento dietético potencialmente protector en la prevención de enfermedades con función mitocondrial alterada.

Prevention of Decompression Sickness by Novel Artificial Oxygen Carriers.

For three decades, studies have demonstrated the therapeutic efficacy of perfluorocarbon (PFC) in reducing the onset of decompression trauma. However, none of these emulsion-based preparations are accepted for therapeutic use in the western world, mainly because of severe side effects and a long organ retention time. A new development to guarantee a stable dispersion without these disadvantages is the encapsulation of PFC in nanocapsules with an albumin shell. PURPOSE: Newly designed albumin-derived perfluorocarbon-based artificial oxygen carriers (A-AOC) are used in a rodent in vivo model as a preventive therapy for decompression sickness (DCS). METHODS: Thirty-seven rats were treated with A-AOC (n = 12), albumin nanocapsules filled with neutral oil (A-O-N, n = 12), or 5% human serum albumin solution (A-0-0, n = 13) before a simulated dive. Eleven rats, injected with A-AOC, stayed at normal pressure (A-AOC surface). Clinical, laboratory, and histological evaluations were performed. RESULTS: The occurrence of DCS depended on the treatment group. A-AOC significantly reduced DCS appearance and mortality. Furthermore, a significant improvement of survival time was found (A-AOC compared with A-0-0). Histological assessment of A-AOC-dive compared with A-0-0-dive animals revealed significantly higher accumulation of macrophages, but less blood congestion in the spleen and significantly less hepatic circulatory disturbance, vacuolization, and cell damage. Compared with nondiving controls, lactate and myoglobin showed a significant increase in the A-0-0- but not in the A-AOC-dive group. CONCLUSION: Intravenous application of A-AOC was well tolerated and effective in reducing the occurrence of DCS, and animals showed significantly higher survival rates and less symptoms compared with the albumin group (A-0-0). Analysis of histological results and fast reacting plasma parameters confirmed the preventive properties of A-AOC.

Disturbed Fatty Acid Oxidation, Endoplasmic Reticulum Stress, and Apoptosis in Left Ventricle of Patients With Type 2 Diabetes.

Chronic heart failure is a common complication in patients with type 2 diabetes mellitus (T2DM). T2DM is associated with disturbed metabolism of fat, which can result in excessive accumulation of lipids in cardiac muscle. In the current study, we assessed mitochondrial oxidation of carbohydrates and fatty acids, lipid accumulation, endoplasmic reticulum (ER) stress, and apoptosis in diabetic left ventricle. Left ventricular myocardium from 37 patients (a group of patients with diabetes and a group of patients without diabetes [ejection fraction >50%]) undergoing coronary artery bypass graft surgery was obtained by subepicardial needle biopsy. The group with diabetes had a significantly decreased rate of mitochondrial respiration fueled by palmitoyl-carnitine that correlated with blood glucose dysregulation, while there was no difference in oxidation of pyruvate. Diabetic myocardium also had significantly decreased activity of hydroxyacyl-CoA dehydrogenase (HADHA) and accumulated more lipid droplets and ceramide. Also, markers of ER stress response (GRP78 and CHOP) and apoptosis (cleaved caspase-3) were elevated in diabetic myocardium. These results show that, even in the absence of contractile failure, diabetic heart exhibits a decreased mitochondrial capacity for ß-oxidation, increased accumulation of intracellular lipids, ER stress, and greater degree of apoptosis. Lower efficiency of mitochondrial fatty acid oxidation may represent a potential target in combating negative effects of diabetes on the heart.

Exercise Reveals Proline Dehydrogenase as a Potential Target in Heart Failure.

The benefits of physical activity in cardiovascular diseases have long been appreciated. However, the molecular mechanisms that trigger and sustain the cardiac benefits of exercise are poorly understood, and it is anticipated that unveiling these mechanisms will identify novel therapeutic targets. In search of these mechanisms we took advantage of unbiased RNA-sequencing (RNA-seq) technology to discover cardiac gene targets whose expression is disrupted in heart failure (HF) and rescued by exercise in a rat model. Upon exhaustive validation in a separate rat cohort (qPCR) and human datasets, we shortlisted 16 targets for a cell-based screening, aiming to evaluate whether targeted disruption of these genes with silencing RNA would affect the abundance of a CVD biomarker (BNP, B-type natriuretic peptide) in human cardiomyocytes. Overall, these experiments showed that Proline Dehydrogenase (PRODH) expression is reduced in human failing hearts, rescued by exercise in a rat model of HF, and its targeted knockdown increases BNP expression in human cardiomyocytes. On the other hand, overexpression of PRODH increases the abundance of metabolism-related gene transcripts, and PRODH appears to be crucial to sustain normal mitochondrial function and maintenance of ATP levels in human cardiomyocytes in a hypoxic environment, as well as for redox homeostasis in both normoxic and hypoxic conditions. Altogether our findings show that PRODH is a novel molecular target of exercise in failing hearts and highlight its role in cardiomyocyte physiology, thereby proposing PRODH as a potential experimental target for gene therapy in HF.

Helicobacter pylori infection and severity of coronary atherosclerosis in patients with chronic coronary artery disease.

AIM: Controversy exists concerning the relation between Helicobacter pylori (HP) infection and coronary artery disease (CAD). We aimed to examine the relationship between HP infection and severity of coronary atherosclerosis in patients with chronic CAD. PATIENTS AND METHODS: A total of 150 patients (109 [73%] men; mean age 62.61±10.23 years) scheduled for coronary artery bypass grafting surgery were consecutively enrolled in the cross-sectional study. According to rapid urease test and/or gastric biopsy samples stained with hematoxylin and eosin and according to Giemsa, patients were classified as HP positive (n=87; 58%) or HP negative (n=63; 42%). Coronary angiograms were scored by quantitative assessment, using multiple angiographic scoring system: 1) vessel score (number of coronary arteries stenosed ≥50%), 2) Gensini score (assigning a severity score to each coronary stenosis according to the degree of luminal narrowing and its topographic importance) and 3) angiographic severity score (number of coronary artery segments stenosed ≥50%). RESULTS: In comparison to HP-negative patients, HP-positive patients were more frequently hypertensive (P=0.014), had higher values of systolic (P=0.043) and diastolic (P=0.005) blood pressure and total cholesterol (P=0.013) and had lower values of high-density lipoprotein-cholesterol (HDL-C; P=0.010). There were no significant differences between the groups in the severity of coronary atherosclerosis: vessel score (P=0.152), Gensini score (P=0.870) and angiographic severity score (P=0.734). CONCLUSION: It is likely that HP infection is not a risk factor for the severity of coronary atherosclerosis in chronic CAD patients.

The impact of predive exercise on repetitive SCUBA diving.

AIM: SCUBA diving frequently involves repetitive exposures. The goal of this study was to see how exercise impacts microparticles (MPs), endothelial function and venous gas emboli (VGE) throughout multiple dives. METHODS: Sixteen divers in two groups (G1 and G2) each completed six dives, three preceded by exercise (EX) and three as controls (CON). Blood for MP analysis was collected before and after each dive. VGE were monitored via transthoracic echocardiography 30, 60 and 90 min after surfacing. Exercise before diving consisted of 60-min running including eight, 3-min intervals at 90% VO2max. RESULTS: Exercise did not have a significant impact on VGE. There was no significant difference in MP counts between EX and CON. Both groups experienced a significant decrease in MP counts in the last three dives compared to the first three (G1 P = 0·0008, G2 P = 0001). Other indices of neutrophil/platelet interaction (dual-positive CD63/41 and CD62/41) show a significant increase (P = 0·004 and 0·0001) in G2. CONCLUSION: Both groups experienced a significant decrease in MPs at all measurements in the second series of dives compared to the first, regardless of the placement of exercise. Whether this is related to an effect of suppression of MPs or exercise timing is not clear.

Impact of Percutaneous Coronary Intervention on Exercise-Induced Repolarization Changes in Patients With Stable Coronary Artery Disease.

Recent reports suggest T peak to T end (Tpe) interval and Tpe/QT ratio as valuable indicators of increased arrhythmogenic risk in patients with coronary artery disease (CAD). We aimed to examine the exercise-induced changes in these indexes in patients with stable CAD, before and after percutaneous coronary intervention (PCI). Forty patients were consecutively included in the interventional group (n = 20), with significant lesions (≥75% luminal narrowing) suitable for PCI and in the control group (n = 20), with no significant coronary artery lesions (<50% luminal narrowing). One day before and 30 days after the coronarography, all patients performed treadmill exercise stress testing, and the electrocardiographic (ECG) indexes of repolarization were assessed during baseline and at peak exercise intensity. In the control group, the QT interval, QTc (QT-corrected) interval, Tpe interval, and Tpe/QT ratio measured at peak exercise significantly decreased from baseline values (p = 0.001, p = 0.004, p <0.001, and p = 0.017, respectively). Conversely, in interventional patients before the PCI, an increase in the Tpe interval and the Tpe/QT ratio was observed at exercise (p = 0.009, and p <0.001, respectively), with only the QT interval exhibiting a significant decrease from baseline (p <0.001). Thirty days after the PCI, all the ECG arrhythmogenic indexes measured at peak exercise significantly decreased from baseline values, thus assuming the same trend as detected in controls. In conclusion, restoration of blood supply normalized exercise-induced repolarization changes, suggesting that revascularization of previously ischemic myocardium lowers the cardiac arrhythmogenic potential in patients with stable CAD.

Role of KATP Channels in Beneficial Effects of Exercise in Ischemic Heart Failure.

PURPOSE: Exercise training reduces pathological remodeling and improves cardiac function in ischemic heart failure; however, causal mechanisms underlying the cardiac benefits of exercise are poorly understood. Because opening of adenosine triphosphate (ATP)-sensitive K ⁺(KATP) channels protects the heart during myocardial stress, we hypothesized that such a mechanism is responsible for some of the cardiac benefits induced by exercise in postinfarction chronic heart failure (CHF). METHODS: Left ventricular myocytes were isolated from three groups of rats: Sham, CHF Tr (4 wk after myocardial infarction, rats underwent 8 wk of aerobic interval training 5 d·wk⁻¹) and CHF Sed (rats sedentary for 12 wk after infarction). Cardiomyocyte survival after oxidative stress exposure (200 µM H2O2) and calcium handling (cells loaded with Fura-2 AM and electrically paced at 1 Hz) were assessed in the presence of KATP channel inhibitor glibenclamide. Expression of KATP subunits (SUR2A and Kir6.2) was evaluated using immunoblotting. RESULTS: Exercise improved cardiac function in CHF Tr animals. Cardiomyocytes from CHF Sed rats were more susceptible to oxidative stress-induced cell death than CHF Tr and Sham cardiomyocytes, with glibenclamide completely abolishing the protective effect of exercise. Glibenclamide did not affect cardiomyocyte survival in Sham or CHF Sed rats. In addition, exercise increased the systolic Ca²âº transient amplitude and improved diastolic Ca²âº removal in CHF Tr cardiomyocytes (compared with CHF Sed); both were significantly attenuated by glibenclamide. Exercise resulted in increased expression of KATP channel subunits in CHF Tr hearts, with more pronounced and significant effect on SUR2A. CONCLUSIONS: Our data suggest that KATP channel upregulation induced by chronic exercise likely mediates some of exercise-induced beneficial effects on cardiac function in postischemic heart failure.

Intrapulmonary shunt and SCUBA diving: another risk factor?

Laboratory and field investigations have demonstrated that intrapulmonary arteriovenous anastomoses (IPAVA) may provide an additional means for venous gas emboli (VGE) to cross over to the arterial circulation due to their larger diameter compared to pulmonary microcirculation. Once thought to be the primary cause of decompression sickness (DCS), it has been demonstrated that, even in large quantities, their presence does not always result in injury. Normally, VGE are trapped in the site of gas exchange in the lungs and eliminated via diffusion. When VGE crossover takes place in arterial circulation, they have the potential to cause more harm as they are redistributed to the brain, spinal column, and other sensitive tissues. The patent foramen ovale (PFO) was once thought to be the only risk factor for an increase in arterialization; however, IPAVAs represent another pathway for this crossover to occur. The opening of IPAVAs is associated with exercise and hypoxic gas mixtures, both of which divers may encounter. The goal of this review is to describe how IPAVAs may impact diving physiology, specifically during decompression, and what this means for the individual diver as well as the future of commercial and recreational diving. Future research must continue on the relationship between IPAVAs and the environmental and physiological circumstances that lead to their opening and closing, as well as how they may contribute to diving injuries such as DCS.

Very Few Exercise-Induced Arterialized Gas Bubbles Reach the Cerebral Vasculature.

INTRODUCTION: Arterialization of venous gas emboli (VGE) formed after surfacing from SCUBA diving can become arterial gas emboli (AGE) through intrapulmonary arterial-venous anastomoses that open with exercise. METHODS: We recruited twenty patent foramen ovale-negative SCUBA divers and conducted a field and a laboratory study with the aim of investigating the appearance of AGE in intracranial vessels. At the field, they performed a single dive to a depth of 18-m sea water with a 47-min bottom time and a direct ascent to the surface. Transthoracic echocardiography was used to score VGE and AGE, and transcranial Doppler was used to visualize middle and posterior cerebral arteries with automated objective bubble detection. Observations were conducted for 45-min after dive at rest and at the laboratory after agitated saline injection at rest and throughout an incremental cycle supine exercise test until exhaustion and for 10 min of recovery. RESULTS: After resurfacing, all divers presented endogenous VGE and arterialization was present in three divers. Saline contrast injection led to AGE in nine of 19 subjects at rest. AGE that reached the cerebral arteries after dive were recorded in two divers at 60 W, three at 90 W, five at 120 W, six at 150 W, and four at 180 W and in three, four, five, nine, and nine, respectively, after saline contrast injection in the laboratory. All divers had AGE grades of 1 or 2, and only single AGE reached the cerebral vasculature. CONCLUSIONS: These data suggest that few emboli of venous origin reach the brain through exercise-induced intrapulmonary arterial-venous anastomoses but cerebral embolization is not high risk in the studied population.

The impact of consecutive freshwater trimix dives at altitude on human cardiovascular function.

Self-contained underwater breathing apparatus (SCUBA) diving is regularly associated with numerous asymptomatic changes in cardiovascular function. Freshwater SCUBA diving presents unique challenges compared with open sea diving related to differences in water density and the potential for dive locations at altitude. The aim of this study was to evaluate the impact of freshwater trimix diving at altitude on human cardiovascular function. Ten divers performed two dives in consecutive days at 294 m altitude with the surface interval of 24 h. Both dives were at a depth of 45 m with total dive time 29 and 26 min for the first and second dive, respectively. Assessment of venous gas embolization, hydration status, cardiac function and arterial stiffness was performed. Production of venous gas emboli was low, and there were no significant differences between the dives. After the first dive, diastolic blood pressure was significantly reduced, which persisted up to 24 h. Left ventricular stroke volume decreased, and heart rate increased after both dives. Pulse wave velocity was unchanged following the dives. However, the central and peripheral augmentation index became more negative after both dives, indicating reduced wave reflection. Ejection duration and round trip travel time were prolonged 24 h after the first dive, suggesting longer-lasting suppression of cardiac and endothelial function. This study shows that freshwater trimix dives with conservative profiles and low venous gas bubble loads can result in multiple asymptomatic acute cardiovascular changes some of which were present up to 24 h after dive.

High intensity cycling before SCUBA diving reduces post-decompression microparticle production and neutrophil activation.

BACKGROUND: Venous gas emboli (VGE) have traditionally served as a marker for decompression stress after SCUBA diving and a reduction in bubble loads is a target for precondition procedures. However, VGE can be observed in large quantities with no negative clinical consequences. The effect of exercise before diving on VGE has been evaluated with mixed results. Microparticle (MP) counts and sub-type expression serve as indicators of vascular inflammation and DCS in mice. The goal of the present study is to evaluate the effect of anaerobic cycling (AC) on VGE and MP following SCUBA diving. METHODS: Ten male divers performed two dives to 18 m for 41 min, one dive (AC) was preceded by a repeated-Wingate cycling protocol; a control dive (CON) was completed without exercise. VGE were analyzed at 15, 40, 80, and 120 min post-diving. Blood for MP analysis was collected before exercise (AC only), before diving, 15 and 120 min after surfacing. RESULTS: VGE were significantly lower 15 min post-diving in the AC group, with no difference in the remaining measurements. MPs were elevated by exercise and diving, however, post-diving elevations were attenuated in the AC dive. Some markers of neutrophil elevation (CD18, CD41) were increased in the CON compared to the AC dive. CONCLUSIONS: The repeated-Wingate protocol resulted in an attenuation of MP counts and sub-types that have been related to vascular injury and DCS-like symptoms in mice. Further studies are needed to determine if MPs represent a risk factor or marker for DCS in humans.

Effects of scuba diving on vascular repair mechanisms.

A single air dive causes transient endothelial dysfunction. Endothelial progenitor cells (EPCs) and circulating angiogenic cells (CAC) contribute synergistically to endothelial repair. In this study (1) the acute effects of diving on EPC numbers and CAC migration and (2) the influence of the gas mixture (air/nitrox-36) was investigated. Ten divers performed two dives to 18 meters on Day (D) 1 and D3, using air. After 15 days, dives were repeated with nitrox-36. Blood sampling took place before and immediately after diving. Circulating EPCs were quantified by flow cytometry, CAC migration of culture was assessed on D7. When diving on air, a trend for reduced EPC numbers is observed post-dive, which is persistent on D1 and D3. CAC migration tends to improve acutely following diving. These effects are more pronounced with nitrox-36 dives. Diving acutely affects EPC numbers and CAC function, and to a larger extent when diving with nitrox-36. The diving-induced oxidative stress may influence recruitment or survival of EPC. The functional improvement of CAC could be a compensatory mechanism to maintain endothelial homeostasis.

Exercise before scuba diving ameliorates decompression-induced neutrophil activation.

INTRODUCTION: The goals of this study were to investigate the difference in responses between a scuba dive preceded by aerobic exercise (EX) and a nonexercise control dive (CON) and to further evaluate the potential relation between venous gas emboli (VGE) and microparticles (MP). We hypothesized that exercise would alter the quantity and subtype of annexin V-positive MP and VGE. METHODS: Nineteen divers performed two dives to 18 m seawater for 41 min separated by at least 3 d, one of which was preceded by 60 min of treadmill interval exercise. Blood was obtained before exercise, before diving, and 15 min, 2 h, 4 h, and 24 h after surfacing. Intravascular bubbles were quantified by transthoracic echocardiography at 15, 40, 80, and 120 min. RESULTS: The median VGE remained unchanged between the two dives; however, there was a significant increase in VGE in the exercise dive at 40 and 80 min at rest. MP were significantly elevated by approximately 2 times at all time points after CON compared with those after EX. Markers of neutrophil and platelet activation were elevated by both dives, and these elevations were attenuated in the EX dive. CONCLUSIONS: We conclude that some of the differences observed between the EX and CON related to MP and platelet and neutrophil activation provide additional insight into the potential protective benefits of exercise; however, further study is needed to understand the mechanism and true potential of these benefits.

Acute and potentially persistent effects of scuba diving on the blood transcriptome of experienced divers.

During scuba diving, the circulatory system is stressed by an elevated partial pressure of oxygen while the diver is submerged and by decompression-induced gas bubbles on ascent to the surface. This diving-induced stress may trigger decompression illness, but the majority of dives are asymptomatic. In this study we have mapped divers' blood transcriptomes with the aim of identifying genes, biological pathways, and cell types perturbed by the physiological stress in asymptomatic scuba diving. Ten experienced divers abstained from diving for >2 wk before performing a 3-day series of daily dives to 18 m depth for 47 min while breathing compressed air. Blood for microarray analysis was collected before and immediately after the first and last dives, and 10 matched nondivers provided controls for predive stationary transcriptomes. MetaCore GeneGo analysis of the predive samples identified stationary upregulation of genes associated with apoptosis, inflammation, and innate immune responses in the divers, most significantly involving genes in the TNFR1 pathway of caspase-dependent apoptosis, HSP60/HSP70 signaling via TLR4, and NF-κB-mediated transcription. Diving caused pronounced shifts in transcription patterns characteristic of specific leukocytes, with downregulation of genes expressed by CD8+ T lymphocytes and NK cells and upregulation of genes expressed by neutrophils, monocytes, and macrophages. Antioxidant genes were upregulated. Similar transient responses were observed after the first and last dive. The results indicate that sublethal oxidative stress elicits the myeloid innate immune system in scuba diving and that extensive diving may cause persistent change in pathways controlling apoptosis, inflammation, and innate immune responses.