Hyperbaric Oxygen Therapy Improves the Osteogenic and Vasculogenic Properties of Mesenchymal Stem Cells in the Presence of Inflammation In Vitro.

Hyperbaric oxygen (HBO) therapy has been reported to be beneficial for treating many conditions of inflammation-associated bone loss. The aim of this work was to in vitro investigate the effect of HBO in the course of osteogenesis of human Mesenchymal Stem Cells (MSCs) grown in a simulated pro-inflammatory environment. Cells were cultured with osteogenic differentiation factors in the presence or not of the pro-inflammatory cytokine Tumor Necrosis Factor-α (TNF-α), and simultaneously exposed daily for 60 min, and up to 21 days, at 2,4 atmosphere absolute (ATA) and 100% O2. To elucidate osteogenic differentiation-dependent effects, cells were additionally pre-committed prior to treatments. Cell metabolic activity was evaluated by means of the MTT assay and DNA content quantification, whereas osteogenic and vasculogenic differentiation was assessed by quantification of extracellular calcium deposition and gene expression analysis. Metabolic activity and osteogenic properties of cells did not differ between HBO, high pressure (HB) alone, or high oxygen (HO) alone and control if cells were pre-differentiated to the osteogenic lineage. In contrast, when treatments started contextually to the osteogenic differentiation of the cells, a significant reduction in cell metabolic activity first, and in mineral deposition at later time points, were observed in the HBO-treated group. Interestingly, TNF-α supplementation determined a significant improvement in the osteogenic capacity of cells subjected to HBO, which was not observed in TNF-α-treated cells exposed to HB or HO alone. This study suggests that exposure of osteogenic-differentiating MSCs to HBO under in vitro simulated inflammatory conditions enhances differentiation towards the osteogenic phenotype, providing evidence of the potential application of HBO in all those processes requiring bone regeneration.

Clinical and morphological effects of hyperbaric oxygen therapy in patients with interstitial cystitis associated with fibromyalgia.

BACKGROUND: Interstitial Cystitis (IC) is a debilitating disorder of the bladder, with a multifactorial and poorly understood origin dealing with microcirculation repeated damages. Also Fibromyalgia (FM) is a persistent disorder whose etiology is not completely explained, and its theorized alteration of pain processing can compromise the quality of life. Both these conditions have a high incidence of conventional therapeutic failure, but recent literature suggests a significant beneficial response to Hyperbaric Oxygen Therapy (HBOT). With this study, this study we evaluated the effects of HBOT on quality of life, symptoms, urodynamic parameters, and cystoscopic examination of patients suffering from both IC and FM. METHODS: We structured an observational clinical trial design with repeated measures (questionnaires, urodynamic test, and cystoscopy) conducted before and 6 months after a therapeutic protocol with hyperbaric oxygen for the treatment of patients suffering from both IC and FM. Patients were exposed to breathing 100% oxygen at 2 atm absolute (ATA) in a multiplace pressure chamber for 90 min using an oro-nasal mask. Patients undertook a cycle of 20 sessions for 5 days per week, and a second cycle of 20 sessions after 1 week of suspension. RESULTS: Twelve patients completed the protocol. Changes after HBOT were not significant, except for hydrodistension tolerance (mean pre-treatment: 409.2 ml; mean post-treatment: 489.2 ml; p < 0.05). A regression of petechiae and Hunner's ulcers was also noted 6 months after the completion of HBOT. CONCLUSIONS: Our study showed no improvement of symptoms, quality of life, and urodynamic parameters, except for hydrodistension, and a slight improvement in cystoscopic pattern. However, to date, we could not demonstrate the significance of overall results to justify the use of HBOT alone in patients with IC and FM. This observation suggests that additional studies are needed to better understand if HBOT could treat this subset of patients. TRIAL REGISTRATION: NCT03693001 ; October 2, 2018. Retrospectively registered.

Hyperbaric oxygen therapy ameliorates osteonecrosis in patients by modulating inflammation and oxidative stress.

Early stages of avascular necrosis of the femoral head (AVNFH) can be conservatively treated with hyperbaric oxygen therapy (HBOT). This study investigated how HBOT modulates inflammatory markers and reactive oxygen species (ROS) in patients with AVNFH. Twenty-three male patients were treated with two cycles of HBOT, 30 sessions each with a 30 days break between cycles. Each session consisted of 90 minutes of 100% inspired oxygen at 2.5 absolute atmospheres of pressure. Plasma levels of tumor necrosis factor alfa (TNF-α), interleukin 6 (IL-6), interleukin 1 beta (IL-1ß) and ROS production were measured before treatment (T0), after 15 and 30 HBOT sessions (T1 and T2), after the 30-day break (T3), and after 60 sessions (T4). Results showed a significant reduction in TNF-α and IL-6 plasma levels over time. This decrease in inflammatory markers mirrored observed reductions in bone marrow edema and reductions in patient self-reported pain.

An overview of protective strategies against ischemia/reperfusion injury: The role of hyperbaric oxygen preconditioning.

Introduction: Ischemia/reperfusion (I/R) injury, such as myocardial infarction, stroke, and peripheral vascular disease, has been recognized as the most frequent causes of devastating disorders and death currently. Protective effect of various preconditioning stimuli, including hyperbaric oxygen (HBO), has been proposed in the management of I/R. Methods: In this study, we searched and reviewed up-to-date published papers to explore the pathophysiology of I/R injury and to understand the mechanisms underlying the protective effect of HBO as conditioning strategy. Results: Animal study and clinic observation support the notion that HBO therapy and conditioning provide beneficial effect against the deleterious effects of postischemic reperfusion. Several explanations have been proposed. The first likely mechanism may be that HBO counteracts hypoxia and reduces I/R injury by improving oxygen delivery to an area with diminished blood flow. Secondly, by reducing hypoxia-ischemia, HBO reduces all the pathological events as a consequence of hypoxia, including tissue edema, increased affective area permeability, postischemia derangement of tissue metabolism, and inflammation. Thirdly, HBO may directly affect cell apoptosis, signal transduction, and gene expression in those that are sensitive to oxygen or hypoxia. HBO provides a reservoir of oxygen at cellular level not only carried by blood, but also by diffusion from the interstitial tissue where it reaches high concentration that may last for several hours, improves endothelial function and rheology, and decreases local inflammation and edema. Conclusion: Evidence suggests the benefits of HBO when used as a preconditioning stimulus in the setting of I/R injury. Translating the beneficial effects of HBO into current practice requires, as for the "conditioning strategies", a thorough consideration of risk factors, comorbidities, and comedications that could interfere with HBO-related protection.

Spirometry and oxidative stress after rebreather diving in warm water.

INTRODUCTION: Hyperbaric oxygen (HBO2) therapy and use of enriched air can result in oxidative injury affecting the brain, lungs and eyes. HBO2 exposure during diving can lead to a decrease in respiratory parameters. However, the possible effects of acute exposure to oxygen-enriched diving on subsequent spirometric performance and oxidative state in humans have not been recently described recently. We aim to investigate possible effects of acute (i) hyperbaric and (ii) hyperbaric hyperoxic exposure using scuba or closed-circuit rebreather (CCR) on subsequent spirometry and to assess the role of oxidative state after hyperoxic diving. METHODS: Spirometry and urine samples were obtained from six well-trained divers (males, mean ± SD, age: 43.33 ± 9.16 years; weight: 79.00 ± 4.90 kg; height: 1.77 ± 0.07 meters) before (CTRL) and after a dive breathing air, and after a dive using CCR (PO2 1.4). In the crossover design (two dives separated by six hours) each subject performed a 20-minute session of light underwater exercise at a depth of 15 meters in warm water (31-32°C). We measured urinary 8-isoprostane and 8-OH-2-deoxyguanosine evaluating lipid and DNA oxidative damages. RESULTS: Different breathing conditions (air vs. CCR) did not significantly affect spirometry. A significant increase of 8-OH-dG (1.85 ± 0.66 vs. 4.35 ± 2.12; P ⟨ 0.05) and 8-isoprostane (1.35 ± 0.20 vs. 2.59 ± 0.61; P ⟨ 0.05) levels after CCR dive with respect to the CTRL was observed. Subjects did not have any ill effects during diving. CONCLUSIONS: Subjects using CCR showed elevated oxidative stress, but this did not correlate with a reduction in pulmonary function.

Effect of mild hyperbaric oxygen therapy on children diagnosed with autism.

INTRODUCTION: Hyperbaric oxygen (HBO2) therapy is emerging internationally as the primary treatment modality for inflammatory pathways related to neurological disorders. Currently, literature concerning its effectiveness in autistic children is limited. Using neurocognitive tests and clinical-diagnostic evaluations, this study evaluates the clinical, cognitive and behavioral effects of HBO2 on children diagnosed with autism. METHODS: An experimental HBO2 group (EXP: F = 1; M = 7; mean age: 7 ± 2.33; years) and a control non-HBO2 group of autistic children (CTRL: F = 2; M= 5; mean age: 6.6 ± 2.7 years) correctly completed the Aberrant Behavior Checklist-Community (ABC) before HBO2 (T0), after 40 sessions of HBO2 (T1), and one month after the end of treatments (T2). Additionally, the experimental HBO2 group was evaluated with the Childhood Autism Rating Scale at T0 and T2. RESULTS: Total ABC score was lower at T2 (mean ± SD: 50.38 ± 18.55; p ⟨ 0.001) compared to scores obtained at T0 (mean ± SD: 57.5 ± 19.01). Similarly, in the control group the total ABC score differed statistically (p ⟨ 0.05) between T0 (103.6 ± 20.38) and (T2: 59 ± 25.25). CONCLUSION: Despite the improvements reported in both groups, our results do not support the utility of HBO2 in children diagnosed with autism..

Cave canem: HBO2 therapy efficacy on Capnocytophaga canimorsus infections: a case series.

BACKGROUND: Dog bites are a frequent injury, but the incidence and type of lesions vary across countries. Although only few patients develop complications, the treatment of advanced injuries has a considerable medical, social and economic impact. A frequently isolated pathogen in dog bite wounds is Capnocytophaga canimorsus, a bacterium that can cause sepsis or meningitis. Hyperbaric oxygen (HBO2) therapy has been shown to be useful in treating anaerobic infections, most likely because it creates an inhospitable environment for the bacterium and enhances the patient's immune response. AIM: We present a case series of C. canimorsus infections treated with HBO2 in adjunction to antibiotic therapy. Furthermore, we tested the in vitro activity of ceftaroline against C. canimorsus, alone and in association with hyperbaric oxygen therapy. METHODS: We included nine (9) patients admitted to the surgery department of "A. Cardarelli" Hospital (Naples) after dog bite, from 2010 to 2016. All were initially treated with antibiotics and required transfer to the intensive care unit due to worsening conditions. C. canimorsus was isolated from wounds, and HBO2 therapy was administered in adjunction to antibiotics, until clinical improvement and microbiological test negativity. We tested the activity of hyperbaric oxygen therapy in adjunction to ceftaroline on cultured plates with C. canimorsus versus ceftaroline alone. Minimal inhibitory concentration was evaluated. CONCLUSIONS: Our findings confirm the utility of HBO2 therapy after biting injuries. Indeed, increased oxygen supply to the wound (as well as in vitro) may be toxic for bacteria, can improve healing and may improve the effectiveness of antibiotics.

Hyperbaric oxygen therapy modulates serum OPG/RANKL in femoral head necrosis patients.

Hyperbaric oxygen therapy (HBOT) has beneficial effects on avascular necrosis of femoral head (ANFH), but its mechanism of action is still unclear. We investigated if HBOT upregulates serum osteoprotegerin (OPG) and/or inhibits osteoclast activation. 23 patients with unilateral ANFH at stage I, II and III consented to the study: the patients received standard HBOT. Serum OPG levels were obtained at the beginning of HBOT (T0), after 15 sessions (T1), 30 sessions (T2), after a 30-day break (T3), and after 60 sessions (T4). Magnetic resonance imaging (MRI) was obtained at T0 and about one year from the end of HBO treatments. Lesion size was compared between pre- and post-HBOT. 19 patients completed the study. HBOT reduced pain symptoms in all patients. HBOT significantly reduced lesion size in all stage I and II patients and in 2 of 11 stage III patients. HBOT increased serum OPG levels but receptor activator of nuclear factor kappa-B ligand (RANKL) levels did not change.