Exploiting a Rose Bengal-bearing, oxygen-producing nanoparticle for SDT and associated immune-mediated therapeutic effects in the treatment of pancreatic cancer.

Sonodynamic therapy (SDT) is an emerging stimulus-responsive approach for the targeted treatment of solid tumours. However, its ability to generate stimulus-responsive cytotoxic reactive oxygen species (ROS), is compromised by tumour hypoxia. Here we describe a robust means of preparing a pH-sensitive polymethacrylate-coated CaO2 nanoparticle that is capable of transiently alleviating tumour hypoxia. Systemic administration of particles to animals bearing human xenograft BxPC3 pancreatic tumours increases oxygen partial pressures (PO2) to 20-50 mmHg for over 40 min. RT-qPCR analysis of expression of selected tumour marker genes in treated animals suggests that the transient production of oxygen is sufficient to elicit effects at a molecular genetic level. Using particles labelled with the near infra-red (nIR) fluorescent dye, indocyanine green, selective uptake of particles by tumours was observed. Systemic administration of particles containing Rose Bengal (RB) at concentrations of 0.1 mg/mg of particles are capable of eliciting nanoparticle-induced, SDT-mediated antitumour effects using the BxPC3 human pancreatic tumour model in immuno-compromised mice. Additionally, a potent abscopal effect was observed in off-target tumours in a syngeneic murine bilateral tumour model for pancreatic cancer and an increase in tumour cytotoxic T cells (CD8+) and a decrease in immunosuppressive tumour regulatory T cells [Treg (CD4+, FoxP3+)] was observed in both target and off-target tumours in SDT treated animals. We suggest that this approach offers significant potential in the treatment of both focal and disseminated (metastatic) pancreatic cancer.

Mitochondria-Targeting Oxygen-Sufficient Perfluorocarbon Nanoparticles for Imaging-Guided Tumor Phototherapy.

BACKGROUND: Although photothermal therapy (PTT) and photodynamics therapy (PDT) have both made excellent progress in tumor therapy, the effectiveness of using PTT or PDT alone is dissatisfactory due to the limitations of the penetration depth in PTT and the hypoxic microenvironment of tumors for PDT. Combination phototherapy has currently become a burgeoning cancer treatment. METHODS AND MATERIALS: In this work, a mitochondria-targeting liquid perfluorocarbon (PFC)-based oxygen delivery system was developed for the synergistic PDT/photothermal therapy (PTT) of cancer through image guiding. RESULTS: Importantly, these nanoparticles (NPs) can effectively and accurately accumulate in the target tumor via the enhanced permeability and retention (EPR) effect. CONCLUSION: This approach offers a novel technique to achieve outstanding antitumor efficacy by an unprecedented design with tumor mitochondria targeting, oxygen delivery, and synergistic PDT/PTT with dual-imaging guidance.

Oxygen self-enriched nanoparticles functionalized with erythrocyte membranes for long circulation and enhanced phototherapy.

In recent years, indocyanine green (ICG) encapsulated in different kinds of nano-carriers have been developed to overcome its short lifetime in vivo and non-selectivity in cancer cells. However, these nanoparticles are still easily recognized and captured by the reticuloendothelial system (RES) and the low singlet oxygen quantum (0.08) of ICG inevitably leads to a limited efficacy of phototherapy. To overcome these limitations, a novel oxygen self-enriched biomimetic red blood cell (RBC) was developed by cloaking albumin nanoparticles which contained ICG and perfluorocarbon (PFC) with RBC membranes. Due to the high oxygen capacity of PFC, the oxygen self-enriched nanoparticles can enhance photodynamic therapy (PDT) by generating more singlet oxygen (1O2). After successfully coated RBC membranes onto nanoparticles, the novel oxygen self-enriched biomimetic RBCs remained the characteristics of photothermal therapy (PTT) and enhanced PDT in vitro. Importantly, it can effectively reduce immune clearance in macrophage cells (RAW264.7) and significantly prolong blood circulation time, achieving high accumulation in tumor. In addition, the tumor growth was effectively inhibited after intravenous injection to tumor-bearing mice. Altogether, this oxygen self-enriched RBCs with long circulation time and high oxygen capacity as natural RBCs provide a new strategy to design biomimetic nano-system for clinical cancer phototherapy treatment. STATEMENT OF SIGNIFICANCE: Near-infrared (NIR) dyes encapsulated in nanocarriers have been achieved great interest in cancer phototherapy treatment. However, the low singlet oxygen (1O2) quantum of NIR dyes and short circulation time of nanoparticles lead to unsatisfactory efficacy, limiting their applications. In this study, a novel oxygen self-enriched biomimetic red blood cell (bio-RBC) was developed to produce fluorescence, imaging-guided for photothermal therapy (PTT) and enhanced photodynamic therapy (PDT). It was composed of RBC membranes and albumin nanoparticles (IPH) which contained indocyanine green (ICG) and perfluorocarbon (PFC). After RBC membranes successfully being coated on nanoparticles, bio-RBC can effectively reduce immune clearance in macrophage cells and achieve longer circulation time in vivo, due to the protein retention in RBC membranes. In addition, PFC with high oxygen capacity can provide more oxygen to generate more 1O2 and dissolve 1O2 to enhance its life-time, enhancing PDT cancer treatment. In summary, the novel bio-RBC with longer lifetime and higher oxygen capacity as natural RBCs can significantly accumulate on tumor and effectively enhance phototherapy. It could serve as a novel strategy to overcome the problems of NIR dyes encapsulated nanoparticles, promising for future clinical application.

Chronic Diseases as Barriers to Oxygen Delivery: A Unifying Hypothesis of Tissue Reoxygenation Therapy.

Modern medical practice has resulted in the accumulation of a growing number of incurable chronic diseases, many of which are inflammatory in nature. Inflammation establishes a hypoxic microenvironment within tissues, a condition of inflammatory hypoxia (IH). Tissues thus affected become severely compromised, are unable to elicit adaptive responses and eventually develop fibrosis and fixed microvascular deficits. Previous work has demonstrated that tissue hypoxia exits even within the simple human model of self-resolving inflammation, the tuberculin reaction. Failed resolution of IH establishes a vicious cycle within tissues that perpetuates tissue hypoxia and resists standard drug therapies. Diseases such as sepsis, chronic cutaneous wounds, kidney disease, traumatic brain injury, solid tumors, inflammatory bowel disease, and chronic bacterial infections (urinary tract infection, cystic fibrosis) are tissue specific manifestations of chronic IH. Successful reversal of IH, through tissue re-oxygenation therapy (TROT), will break this vicious cycle and restore tissue homeostasis. The examples of solid tumors and inflammatory bowel disease are presented to illustrate a theoretical framework to support this hypothesis. Re-oxygenation of compromised tissues must occur before successful treatment of these diverse chronic disease s can be expected.

CLA supplementation and aerobic exercise lower blood triacylglycerol, but have no effect on peak oxygen uptake or cardiorespiratory fatigue thresholds.

This study examined the effects of 6 weeks of conjugated linoleic acid (CLA) supplementation and moderate aerobic exercise on peak oxygen uptake (VO2 peak), the gas exchange threshold (GET), the respiratory compensation point (RCP), and serum concentrations of cholesterol, triacylglycerol, and glucose in humans. Thirty-four untrained to moderately trained men (mean ± SD; age = 21.5 ± 2.8 years; mass = 77.2 ± 9.5 kg) completed this double-blind, placebo controlled study and were randomly assigned to either a CLA (Clarinol A-80; n = 18) or placebo (PLA; sunflower oil; n = 16) group. Prior to and following 6 weeks of aerobic training (50% VO2 peak for 30 min, twice per week) and supplementation (5.63 g of total CLA isomers [of which 2.67 g was c9, t11 and 2.67 g was t10, c12] or 7.35 g high oleic sunflower oil per day), each participant completed an incremental cycle ergometer test to exhaustion to determine their [Formula: see text] peak, GET, and RCP and fasted blood draws were performed to measure serum concentrations of cholesterol, triacylglycerol, and glucose. Serum triacylglycerol concentrations were lower (p < 0.05) in the CLA than the PLA group. For VO2 peak and glucose, there were group × time interactions (p < 0.05), however, post hoc statistical tests did not reveal any differences (p > 0.05) between the CLA and PLA groups. GET and RCP increased (p < 0.05) from pre- to post-training for both the CLA and PLA groups. Overall, these data suggested that CLA and aerobic exercise may have synergistic, blood triacylglycerol lowering effects, although CLA may be ineffective for enhancing aerobic exercise performance in conjunction with a 6-week aerobic exercise training program in college-age men.

Post-operative atelectasis - a randomised trial investigating a ventilatory strategy and low oxygen fraction during recovery.

BACKGROUND: Atelectasis is common during and after general anaesthesia. We hypothesized that a ventilation strategy with a combination of 1) continuous positive airway pressure (CPAP) or positive end-expiratory pressure (PEEP) and 2) a reduced end-expiratory oxygen concentration during recovery would reduce post-operative atelectasis. METHODS: Sixty patients were randomized into two groups. During anaesthesia induction, inspiratory oxygen fraction (FIO2) was 1.0, and depending on weight, CPAP 6, 7 or 8 cmH2O was applied in both groups via facemask. During maintenance of anaesthesia, a laryngeal mask airway (LMA) was used, and PEEP was 6-8 cmH2O in both groups. Before removal of the LMA, FIO2 was set to 0.3 in the intervention group and 1.0 in the control group. Atelectasis was studied by computed tomography (CT) approximately 14 min post-operatively. RESULTS: In one patient in the group given an FIO2 of 0.3 before removal of the LMA a CT scan could not be performed so the patient was excluded. The area of atelectasis was 5.5, 0-16.9 cm(2) (median and range), and 6.8, 0-27.5 cm(2) in the groups given FIO2 0.3 or FIO2 1.0 before removal of the LMA, a difference that was not statistically significant (P = 0.48). Post-hoc analysis showed dependence of atelectasis on smoking (despite all were clinically lung healthy) and American Society of Anesthesiologists class (P = 0.038 and 0.015, respectively). CONCLUSION: Inducing anaesthesia with CPAP/PEEP and FIO2 1.0 and deliberately reducing FIO2 during recovery before removal of the LMA did not reduce post-operative atelectasis compared with FIO2 1.0 before removal of the LMA.

Enhancement of homocysteine toxicity to insulin-secreting BRIN-BD11 cells in combination with alloxan.

Previous studies have shown that homocysteine (HC) has a detrimental impact on insulin secretion and pancreatic beta cell function. The aim of the present study was to determine the role of reactive oxygen species (ROS) in the in vitro toxic effects of HC on insulin secretion and function of BRIN-BD11 insulin-secreting cells. In this study, insulin secretion from BRIN-BD11 cells was determined radioimmunologically, cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and glucokinase activity by a glucose phosphorylation assay following culture with HC plus alloxan (Alx). Treatment with HC resulted in concentration-dependent inhibition of insulin secretion induced by glucose and other insulinotropic agents. HC in combination with Alx resulted in a more pronounced decline in insulin secretion, including that induced by 20  mM alanine, by 43% (P<0.001) and 30  mM KCl by 60% (P<0.001), compared with control culture. The glucokinase phosphorylating capacity in cells cultured with HC plus Alx was significantly lower, compared with control cells. The cells also displayed a significant 84% (P<0.001) decline in cell viability. Prolonged, 72-h culture of insulin-secreting cells with HC followed by 18-h culture without HC did not result in full restoration of beta cell responses to insulinotropic agents. In vitro oxygen consumption was enhanced by a combination of Alx with HC. The study arrived at the conclusion that HC generates ROS in a redox-cycling reaction with Alx that explains the decline in viability of insulin-secreting cells, leading to reduced glucokinase phosphorylating ability, diminished insulin secretory responsiveness and cell death.

Potential use of fluorocarbons in lung surfactant therapy.

Exogenous surfactant therapy based on animal lung extract preparations has been developed successfully for the treatment of neonatal respiratory distress syndrome. However, because of the inherent limitations of these natural preparations, the development of new synthetic surfactants is a major objective. We report here that a perfluorocarbon gas (perfluorooctyl bromide, gPFOB) inhibits the formation of the semi-crystalline domains that occur during compression of a Langmuir monolayer of dipalmitoyl phosphatidylcholine (DPPC), taken as a simplified model of lung surfactant. gPFOB also facilitates the re-spreading of the DPPC monolayer. These results suggest that PFOB, a fluorocarbon already investigated for oxygen delivery, may be useful in lung surfactant replacement compositions.

Dynamics of intramuscular 31P-MRS P(i) peak splitting and the slow components of PCr and O2 uptake during exercise.

The dynamics of pulmonary O(2) uptake (Vo(2)) during the on-transient of high-intensity exercise depart from monoexponentiality as a result of a "slow component" whose mechanisms remain conjectural. Progressive recruitment of glycolytic muscle fibers, with slow O(2) utilization kinetics and low efficiency, has, however, been suggested as a mechanism. The demonstration of high- and low-pH components of the exercising skeletal muscle (31)P magnetic resonance (MR) spectrum [inorganic phosphate (P(i)) peak] at high work rates (thought to be reflective of differences between oxidative and glycolytic muscle fibers) is also consistent with this conjecture. We therefore investigated the dynamics of Vo(2) (using a turbine and mass spectrometry) and intramuscular ATP, phosphocreatine (PCr), and P(i) concentrations and pH, estimated from the (31)P MR spectrum. Eleven healthy men performed prone square-wave high-intensity knee extensor exercise in the bore of a whole body MR spectrometer. A Vo(2) slow component of magnitude 15.9 +/- 6.9% of the phase II amplitude was accompanied by a similar response (11.9 +/- 7.1%) in PCr concentration. Only five subjects demonstrated a discernable splitting of the P(i) peak, however, which began from between 35 and 235 s after exercise onset and continued until cessation. As such, the dynamics of the pH distribution in intramuscular compartments did not consistently reflect the temporal features of the Vo(2) slow component, suggesting that P(i) splitting does not uniquely reflect the activity of oxidative or glycolytic muscle fibers per se.

Two-stage culture process for improved production of ganoderic acid by liquid fermentation of higher fungus Ganoderma lucidum.

Investigations on the impact of pellet size on the cellular oxygen uptake and accumulation of ganoderic acid (GA) suggested the favorable effect of oxygen limitation on GA formation by the higher fungus Ganoderma lucidum. A two-stage fermentation process was thus proposed for enhanced GA production by combining conventional shake-flask fermentation with static culture. A high cell density of 20.9 g of DW/L (DW = dry cell weight) was achieved through a 4-day shake-flask fermentation followed by a 12-day static culture. A change in the cell morphology and a decrease in the sugar consumption rate were observed during the static culture. The GA production in the new two-stage process was considerably enhanced with its content increased from 1.36 (control) to 3.19 mg/100 mg of DW, which was much higher than previously observed.

Enhanced pyruvate dehydrogenase activity does not affect muscle O2 uptake at onset of intense exercise in humans.

It has been proposed that the activation state of pyruvate dehydrogenase (PDH) may influence the rate of skeletal muscle O2 uptake during the initial phase of exercise; however, this has not been directly tested in humans. To remedy this, we used dichloroacetate (DCA) infusion to increase the active form of PDH (PDH(a)) and, subsequently, measured leg O2 uptake and markers of anaerobic ATP provision during conditions of intense dynamic exercise, when the rate of muscle O2 uptake would be very high. Six subjects performed brief bouts of one-legged knee-extensor exercise at approximately 110% of thigh peak O2 uptake (65.3 +/- 3.7 W) on several occasions: under noninfused control (Con) and DCA-supplemented conditions. Needle biopsy samples from the vastus lateralis muscle were obtained at rest and after 5 s, 15 s, and 3 min of exercise during both experimental conditions. In addition, thigh blood flow and femoral arteriovenous differences for O2 and lactate were measured repeatedly during the 3-min work bouts (Con and DCA) to calculate thigh O2 uptake and lactate release. After DCA administration, PDH(a) was four- to eightfold higher (P < 0.05) than Con at rest, and PDH(a) remained approximately 130% and 100% higher (P < 0.05) after 5 and 15 s of exercise, respectively. There was no difference between trials after 3 min. Despite the marked difference in PDH(a) between trials at rest and during the initial phase of exercise, thigh O2 uptake was the same. In addition, muscle phosphocreatine utilization and lactate production were similar after 5 s, 15 s, and 3 min of exercise in DCA and Con. The present findings demonstrate that increasing PDH(a) does not alter muscle O2 uptake and anaerobic ATP provision during the initial phase of intense dynamic knee-extensor exercise in humans.

A modulatory role for oxygen in shaping rhythmic motor output patterns of neuronal networks.

It is becoming increasingly evident that O(2)-uptake in animal tissue is not only devoted to energy production. Here we review recent findings on a novel role of tissue oxygenation, notably in controlling the operation of neuronal networks in the central nervous system. Electrophysiological recordings in vivo and in vitro from rhythmically-active motor pattern generating networks in the lobster stomatogastric ganglion (STG) have revealed that oxygen is able to act in a manner equivalent to a classical neuromodulator. Local P(O(2)) variations within the low, but physiological range of 1-6 kPa are able to shape ongoing activity of these networks and therefore the motor behaviours in which they are involved. Oxygen's contribution to two of these, feeding and moulting, have been investigated. Importantly, the P(O(2)) effects are not related to hypoxic depression but are highly specific in terms of the network, neuron and even the synapse targeted. Our results are discussed in terms of functional significance and new research directions for mammalian physiology.

Improvement of Panax notoginseng cell culture for production of ginseng saponin and polysaccharide by high density cultivation in pneumatically agitated bioreactors.

A Panax notoginseng cell culture was successfully scaled up from shake flask to 1.0-L bubble column reactor and concentric-tube airlift reactor. High-density bioreactor batch cultivation was carried out using a modified MS medium. The maximum cell density in batch cultures reached 20.1, 21.0 and 24.1 g/L in the shake flask, bubble column and airlift reactors, respectively, and their corresponding biomass productivity was 950, 1140 and 1350 mg/(L x d) for each. The productivity of ginseng saponin was 70, 96 and 99 mg/(L x d) in the flask, bubble column and airlift reactors, respectively; and the polysaccharide productivity reached 104, 119 and 151 mg/(L x d) for each. Furthermore, a fed-batch cultivation strategy was developed on the basis of specific oxygen uptake rate (SOUR), i.e., sucrose feeding before a sharp decrease of SOUR, and the highest cell density of 29.7 g/L was successfully achieved in the airlift bioreactor on day 17 with a very high biomass productivity of 1520 mg/(L x d). The concentrations of ginseng saponin and polysaccharide reached about 2.1 and 3.0 g/L, respectively, and their productivity was 106 (saponin) and 158 mg/(L x d) (polysaccharide). This work successfully demonstrated the high-density bioreactor cultivation of P. notoginseng cells in pneumatically agitated bioreactors and the reproduction of the shake flask culture results in bioreactors. The cell density, biomass productivity, production titer and productivity of both ginseng saponin and polysaccharide obtained here were the highest that have been reported on a reactor scale for all the ginseng species.

The influence of different fluoride compounds and treatment conditions on dental enamel: a descriptive in vitro study of the CaF(2) precipitation and microstructure.

Electron and atomic force microscopy techniques have been applied to characterize both the in vitro deposition intensity and the microstructure of the KOH-soluble fluoride precipitates on human dental enamel. The study was focused on the effects of amine fluoride, sodium fluoride and sodium monofluorophosphate having a fluoride concentration of 0.1% F in acidulated and aqueous solutions. Under certain conditions, fluoride globules were formed within an initiation time of less than 20 s. This result supports the potential significance of this process for the cariostatic action of fluorides during dentifrice use. The deposition intensity seems to be dependent on the availability of Ca and F ions on the dental surface. A nanocrystalline calcium fluoride-like microstructure was revealed, with an additional phosphorus and oxygen incorporation as a function of the treatment time.

Improvement of tumor oxygenation by mild hyperthermia.

There is now abundant evidence that oxygenation in rodent, canine and human tumors is improved during and for up to 1-2 days after heating at mild temperatures. An increase in tumor blood perfusion along with a decline in the oxygen consumption rate appears to account for the improvement of tumor oxygenation by mild hyperthermia. The magnitude of the increase in tumor pO(2), determined with oxygen-sensitive microelectrodes, caused by mild hyperthermia is less than that caused by carbogen breathing. However, mild hyperthermia is far more effective than carbogen breathing in increasing the radiation response of experimental tumors, probably because mild hyperthermia oxygenates both (diffusion-limited) chronically hypoxic and (perfusion-limited) acutely hypoxic cells, whereas carbogen breathing oxygenates only the chronically hypoxic cells. Mild hyperthermia is also more effective than nicotinamide, which is known to oxygenate acutely hypoxic cells, in enhancing the radiation response of experimental tumors. The combination of mild hyperthermia with carbogen or nicotinamide is highly effective in reducing the hypoxic cell fraction in tumors and increasing the radiation response of experimental tumors. A primary rationale for the use of hyperthermia in combination with radiotherapy has been that hyperthermia is equally cytotoxic toward fully oxygenated and hypoxic cells and that it directly sensitizes both fully oxygenated and hypoxic cells to radiation. Such cytotoxicity and such a radiosensitizing effect may be expected to be significant when the tumor temperature is elevated to at least 42-43 degrees C. Unfortunately, it is often impossible to uniformly raise the temperature of human tumors to this level using the hyperthermia devices currently available. However, it is relatively easy to raise the temperature of human tumors into the range of 39-42 degrees C, which is a temperature that can improve tumor oxygenation for up to 1-2 days. The potential usefulness of mild hyperthermia to enhance the response of human tumors to radiotherapy by improving tumor oxygenation merits continued investigation.

The estimation of the diffusion constant and solubility of O(2)in tissue using kinetics.

The diffusion of a gas through a substance in which it is soluble is analogous to the passage of electric current through a circuit with both capacitance and resistance. We model steady-state diffusion employing this analogy, and extend the model to include a description of the kinetics of systems under circumstances of changing partial pressure, applying two physical constants from electrical circuitry to gas diffusion: capacitance (zeta) and resistance (R). We represent the substrate of the diffusion as a capacitor being charged through a resistor after the rapid imposition of a voltage change. Using the insight derived from this model we have devised an experimental system that allows us to approximate both D, the diffusion coefficient, and alpha, solubility, directly from the kinetic data. We do this by recording the exponential change in P(O(2))on one side of a sheet of material both with and without the addition of a purely resistive barrier of known resistivity. The method was used to estimate D and alpha for distilled water at a number of temperatures, olive oil, and the belly skin of Rana catesbeiana.

Role of malate synthesis mediated by phosphoenolpyruvate carboxylase in guard cells in the regulation of stomatal movement.

To clarify the pathway and role of malate synthesis in guard cells, epidermal strips isolated from Vicia faba L. leaflets were treated with 3,3-dichloro-2-dihydroxyphosphinoylmethyl-2-propenoate (DCDP), a specific inhibitor of phosphoenolpyruvate carboxylase (PEPC). When dark-closed stomata were illuminated, malate accumulated in guard cells and stomata opened; these were inhibited by 60% and 30%, respectively, by 5 mM DCDP treatment. When light-opened stomata were treated with DCDP, both malate level in guard cells and stomatal aperture decreased. Treatment with 5 mM DCDP partially inhibited CO2 incorporation into malate in guard cells. Treatment with mannitol at 0.4 M (osmotic stress) in the light increased malate level in guard cells and closed stomata. DCDP treatment decreased both malate level and stomatal aperture under stressed condition. These results show that malate synthesis in the light under both non-stressed and stressed conditions is dependent on PEPC activity. The extent of the decrease in malate level by DCDP treatment was larger under stressed condition than under nonstressed condition, suggesting that osmotic stress may enhance the activity of this pathway of malate synthesis which is induced by light. Role of malate synthesis in guard cells is discussed.

Terapia con oxigenación hiperbárica, concepto básico / Therapy with hyperbaric oxygenation. Basic concepts

La Oxigenación Hiperbárica (OHB) es definida como la terapia en que se respira oxigeno al 100 por ciento en un ambiente presurizado a por lo menos 1.4 atmósferas absolutas. Sus inicios se remontan al S.XV cuando se utilizó para tratar enfermedades respiratorias. Durante algún tiempo sus aplicaciones carecieron de bases científicas hasta mediados de este siglo en que se realizan trabajos apegados a la metodología actual demostrando su aplicación en patologías que tienen de base tienen hipoxia/isquemia.Esta modalidad de tratamiento se fundamenta principalmente en tres leyes de los gases: Ley de Henry, Ley de Dalton y Ley de Boyle. Los beneficios en el organismo, como promoción del proceso de cicatrización, aumento de la capacidad bactericida del neutrófilo, efecto tóxico directo sobre algunos microorganismos, vasoconstricción arteriolar con la consecuente reducción del edema y disminución de la lesión por isquemia reperfusión, entre otros, son como resultado de la presión ambiental aumentada y la hiperoxigenación de los tejidos en el organismo. Actualmente existen 13 condiciones aceptadas por la UHMS para ser tratadas con OHB y varias mas se encuentran en investigación. Siguiendo los protocolos de tratamiento indicados por la UHMS, las complicaciones y/o efectos adversos son escasos.