Hyperbaric Oxygen Administration Research Articles

P08.58 Impact of selected pentabromobenzylisothiourea (ZKK-3) combined with hyperbaric oxygen therapy on therapeutic response and oxygenation status of T98G glioblastoma cell line

Abstract Introduction: Glioblastoma (GBM), the primary brain tumour derived from astroglial cells, is the most frequently diagnosed intracranial malignancy in adults. Poor prognosis for GBM patients results from high invasiveness of neoplastic cells related with faulty angiogenesis and persistent hypoxia states. In such conditions glioma cells develop radio- and chemotherapy-resistant phenotype. It is postulated that application of hyperbaric oxygen (HBO) may improve therapeutic response via refinement of tumour tissue oxygenation. The more effective therapeutic strategies are also required. One of the novel compounds that exhibit anti-tumour properties are pentabromobenzylisothioureas. The aim of this study was to examine whether HBO may enhance anti-tumour efficacy of selected pentabromobenzylisothiourea when both agents were administered as combined ZKK-3/HBO therapy. Materials and Methods: Human glioblastoma T98G cell line was cultured in medium supplemented with novel isothiourea derivative - ZKK-3. The proliferation and viability of glioma cells cultured in hypoxia or hyperbaric oxygen conditions were examined. Cell proliferation was tested 24 hours after ZKK-3 addition using Nikon Inverted Microscope and Multisizer 3 Beckman Coulter. The viability assay was taken 24 and 48 hours post ZKK-3 supplementation by CellTiter 96®AQueous One Solution Cell Proliferation Assay (Promega). Hypoxia state of T98G cells was determined via the evaluation of HIF-1α protein expression using HIF-1A ELISA Kit (Thermo Scientific). Tests were performed on cells treated with ZKK-3 and cultured in various oxygen conditions: 1/ normoxia (24 hours), 2/ hypoxia (24 hours), 3/ HBO (2 ATA, 1 hour followed by 23 hours of normoxia), 4/ double hypoxia, 5/ hypoxia/HBO. Results: Proliferation of T98G cells treated with ZKK-3 was significantly decreased after hyperbaric oxygenation in comparison to hypoxia conditions. Administration of HBO resulted also in statistically significant diminution of glioma cells’ viability. Expression of HIF-1α in T98G cells strongly depended on oxygen conditions: in hypoxia and double hypoxia the level of protein was significantly elevated compared with normoxia, while after hyperbaric oxygenation no changes or even decrease of HIF-1α level was observed. Comparison of double hypoxia and hypoxia/HBO groups showed that HBO addition after ZKK-3 supplementation caused significant reduction of HIF-1α expression. Conclusions: Treatment of malignant glioma cells with selected isothiourea derivative is significantly more efficient when combined with hyperbaric oxygen administration. Beneficial effect of HBO on decreasing HIF-1α expression allows to consider hyperbaric oxygenation as the way to overcome tumour hypoxia.ACKNOWLEDGEMENT: The research was supported by the KNOW-MMRC project and Foundation for the Development of Diagnostic and Therapy.

Hyperbaric oxygen as an adjunctive therapy in treatment of malignancies, including brain tumours.

Hyperbaric oxygen (HBO) therapy is widely used as an adjunctive treatment for various pathological states, predominantly related to hypoxic and/or ischaemic conditions. It also holds promise as an approach to overcoming the problem of oxygen deficiency in the poorly oxygenated regions of the neoplastic tissue. Occurrence of local hypoxia within the central areas of solid tumours is one of the major issues contributing to ineffective medical treatment. However, in anti-cancer therapy, HBO alone gives a limited curative effect and is typically not applied by itself. More often, HBO is used as an adjuvant treatment along with other therapeutic modalities, such as radio- and chemotherapy. This review outlines the existing data regarding the medical use of HBO in cancer treatment, with a particular focus on the use of HBO in the treatment of brain tumours. We conclude that the administration of HBO can provide many clinical benefits in the treatment of tumours, including management of highly malignant gliomas. Applied immediately before irradiation, it is safe and well tolerated by patients, causing rare and limited side effects. The results obtained with a combination of HBO/radiotherapy protocol proved to be especially favourable compared to radiation treatment alone. HBO can also increase the cytostatic effect of certain drugs, which may render standard chemotherapy more effective. The currently available data support the legitimacy of conducting further research on the use of HBO in the treatment of malignancies.

Hyperbaric Oxygen Intervention Modulates Early Brain Injury after Experimental Subarachnoid Hemorrhage in Rats: Possible Involvement of TLR4/NF-κ B-Mediated Signaling Pathway

Background/Aims: Previous studies have proved that the activation of TLR4/NF-κ B signaling pathway is involved in inflammatory processes in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Hyperbaric oxygen (HBO) intervention has successfully been used to treat several animal models of tissue injury via its anti-inflammation property. This study was undertaken to investigate the influence of HBO administration on the TLR4/NF-κ B signaling pathway in rats at the early stage of SAH. Methods: Male Sprague-Dawley rats (n = 150) were randomly divided into 5 groups: the sham, the sham + 2.8 atmospheres absolute (ATA) HBO group, the SAH group, the SAH + 2.0ATA HBO group, the SAH + 2.8ATA HBO group. Each group (n = 30) was randomly subdivided into three subgroups that were examined at the following time points: 24 h, 48 h and 72 h post-injury. HBO (100% O2, 2.0ATA or 2.8ATA for 90mins) was initiated 12 h after injury. Neurological deficit, brain edema and blood-brain barrier (BBB) permeability were assessed to evaluate the development of EBI. The expressions of TLR4, NF-κ B and pro-inflammatory cytokines in the cortical were determined by real time polymerase chain reaction (RT-PCR), western blot, immunohistochemistry, or enzyme-linked immunosorbent assay (ELISA). Results: Our study showed that treatment with HBO significantly decreased the expressions of TLR4, NF-κ B and the downstream inflammatory agents, such as TNF-α, IL-6, IL-1β and ICAM-1, and also improved brain edema, blood-brain barrier permeability and neurologic function. Conclusions: These findings indicate that HBO treatment may result in abatement of the development of EBI after SAH, possibly through suppression of TLR4/NF-κ B signaling pathway.

Effects of Hyperbaric Oxygen and Preconditioning on Wound Healing in Colonic Anastomoses

ABSTRACTAim: The purpose of this study was to evaluate the effects of hyperbaric oxygen (HBO) and HBO preconditioning (pre-HBO) on experimental wound healing and tensile strength in the colonic anastomosis of rats. Materials and Methods: A total of 21 Sprague–Dawley rats were divided into three random groups of equal numbers: sham operation, pre-HBO, and HBO. Sham group was given standard left colon resection and end-to-end anastomosis; pre-HBO group received HBO as one dose + colonic resection + anastomosis; HBO group was given colonic resection + anastomosis + HBO. HBO was administrated at 24-hr intervals and relaparatomy was performed on the fifth day. Malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), interleukin (IL)-10, IL-6, tumor necrosis factor-alpha (TNF-α), and hydroxy (OH)-proline levels and anastomotic burst pressure were evaluated. Results: Burst pressure and OH-proline levels markedly increased in the HBO group compared with the sham and pre-HBO groups. When compared with the sham group, MDA and MPO levels were significantly decreased in the HBO and pre-HBO groups. In contrast to these findings, SOD and GSH-Px levels were increased in the HBO group as compared with the sham and pre-HBO groups. TNF-α, IL-6, and IL-10 values were detected at low levels in the HBO group as compared with other groups. Conclusions: HBO administration accelerated wound healing and strengthened the anastomotic tissue. In the light of these results, the HBO administration has beneficial effects and contributed to wound healing in colonic anastomosis. But, as expected, pre-HBO did not alter the results significantly.

Cognitive enhancement of healthy young adults with hyperbaric oxygen: A preliminary resting-state fMRI study

ObjectiveTo date, no study has examined the effect of hyperbaric oxygen (HBO) on the cognitive performance and spontaneous brain activity in healthy adults using resting-state functional magnetic resonance imaging (rsfMRI). Our aim was to reveal the neural mechanism underlying the change in cognitive performance caused by increased oxygen. MethodsIn this study, we acquired fMRI data from 20 healthy young adults and used placebo-controlled (PBO) rsfMRI to identify the effect of HBO on the cognitive measures and the regional homogeneity (ReHo) in healthy adults. ResultsCompared to the PBO group, the HBO group showed the following: (1) the scores of the spatial working memory and memory quotient were significantly increased after HBO administration; (2) the ReHo value was significantly increased in three clusters, the left hippocampus, right inferior frontal, and lingual gyri, and for these three clusters, their functional connectivity with the subcortical brain system was significantly increased after HBO administration; and (3) the changes of ReHo values in these clusters generated by HBO administration were correlated with several aspects of cognitive performance, clarifying the cognitive locus of the effect. ConclusionOur results suggested that the increased availability of oxygen can, to some extent, improve memory performance. SignificantOur findings may improve our understanding of the role of HBO in clinical and practical applications.

A new utilization area for hyperbaric oxygen? Improving quality of stored blood.

Since blood bags have the ability for diffusion of gases, we investigated whether hyperbaric oxygen (HBO) exposure affects several vital parameters of stored blood. Bloods obtained from the same persons were used as both control and HBO groups and stored in pediatric bags with citrate-phosphate-dextrose solution. HBO administration was performed at 2.5 atm for 90 min, started 1 day after blood collection and repeated every 2 days for a total of 10 times. The study was terminated on the 21st day. Complete blood count, glucose, pH, and osmotic fragility values were measured every week. Glucose and pH levels decreased in stored blood. In the HBO-exposed group, these decreases were less than in the control. In addition, mean corpuscular and platelet volumes tended to increase during storing process, but with HBO, these indexes remained lower, near physiologic levels. Another interesting finding of the study was the relative stable osmotic fragility ratio in the HBO group compared to the control blood. HBO exposure has positive effects on pH, stability of erythrocytes, and energy source (glucose) of the medium. Thus, we concluded that HBO may be a useful application for life and quality of stored blood.

The apoptosis of peripheral blood lymphocytes promoted by hyperbaric oxygen treatment contributes to attenuate the severity of early stage acute pancreatitis in rats

The aim of this study was to investigate the immunoregulatory effects of hyperbaric oxygen (HBO) via promoting the apoptosis of peripheral blood lymphocytes (PBLs) to attenuate the severity of early stage acute pancreatitis (AP) in rats. Additionally, the persistence of the HBO treatment effects was evaluated. One hundred and twenty male Wistar rats were randomized into four groups: sham, AP, AP + normobaric oxygen (NBO), and AP + HBO. Each group consisted of 30 rats. Four hours after the induction of AP, the 30 rats in the AP + NBO group were given normobaric oxygen treatment with 100 % oxygen at 1 atm for 90 min. The 30 rats in the AP + HBO group received 100 % oxygen at 2.5 atm for 90 min, with a compression/decompression time of 15 min. The 30 rats in the AP group remained untreated. At 6, 12, and 24 h after the induction of AP, surviving rats from each group were sacrificed, and the blood and tissue samples were collected for the following measurements: the partial pressure of oxygen (PaO2) and oxygen saturation (SaO2) of the arterial blood, the levels of serum amylase, lipase, interleukin-2 (IL-2), interferon-γ (IFN-γ), interleukin-10 (IL-10), hepatocyte growth factor (HGF), and reactive oxygen species (ROS), and the mitochondrial membrane potential (∆Ψm) of the PBLs. The expression levels of procaspase-3, caspase-3, procaspase-9, and caspase-9 were also evaluated in the PBLs. Additionally, the apoptosis of PBLs was assessed, and the pancreatic tissues were subjected to a histopathological analysis by pathological grading and scoring. The histopathology of the lung, liver, kidney, duodenum, and heart was also analyzed at 12 h after the induction of AP. Significant differences were found at 6 and 12 h after AP induction. The HBO treatment significantly elevated the PaO2 and SaO2 levels, and the ROS levels in the PBLs. Additionally, HBO downregulated the levels of amylase and lipase. The HBO treatment also reduced the ∆Ψm levels, upregulated the expression of caspase-3 and caspase-9, and increased the apoptosis rate of the PBLs. Moreover, the HBO treatment decreased the serum concentrations of IL-2, IFN-γ and HGF, and reduced the pathological scores of the pancreatic tissue. The histopathological changes of the lung, liver, kidney, duodenum, and heart were also improved. A significant elevation of IL-10 occurred only at the 12-h time point. However, no obvious differences were found at the 24-h time point. This study demonstrated that the HBO treatment can promote the apoptosis of PBLs via a mitochondrial-dependent pathway and inhibit the inflammatory response. These immunoregulatory effects may play an important therapeutic role in attenuating the severity of early stage AP. The repeated administration of HBO or the use of HBO in combination with other approaches may further improve outcomes.

Combined administration of hyperbaric oxygen and hydroxocobalamin improves cerebral metabolism after acute cyanide poisoning in rats

Hyperbaric oxygen therapy (HBOT) or intravenous hydroxocobalamin (OHCob) both abolish cyanide (CN)-induced surges in interstitial brain lactate and glucose concentrations. HBOT has been shown to induce a delayed increase in whole blood CN concentrations, whereas OHCob may act as an intravascular CN scavenger. Additionally, HBOT may prevent respiratory distress and restore blood pressure during CN intoxication, an effect not seen with OHCob administration. In this report, we evaluated the combined effects of HBOT and OHCob on interstitial lactate, glucose, and glycerol concentrations as well as lactate-to-pyruvate ratio in rat brain by means of microdialysis during acute CN poisoning. Anesthetized rats were allocated to three groups: 1) vehicle (1.2 ml isotonic NaCl intra-arterially); 2) potassium CN (5.4 mg/kg intra-arterially); 3) potassium CN, OHCob (100 mg/kg intra-arterially) and subsequent HBOT (284 kPa in 90 min). OHCob and HBOT significantly attenuated the acute surges in interstitial cerebral lactate, glucose, and glycerol concentrations compared with the intoxicated rats given no treatment. Furthermore, the combined treatment resulted in consistent low lactate, glucose, and glycerol concentrations, as well as in low lactate-to-pyruvate ratios compared with CN intoxicated controls. In rats receiving OHCob and HBOT, respiration improved and cyanosis disappeared, with subsequent stabilization of mean arterial blood pressure. The present findings indicate that a combined administration of OHCob and HBOT has a beneficial and persistent effect on the cerebral metabolism during CN intoxication.

The effects of hyperbaric air and hyperbaric oxygen on blood–brain barrier integrity in rats

Hyperbaric oxygen (HBO) treatment yields conflicting results on blood–brain barrier (BBB) integrity under various pathological conditions and the effects of HBO on healthy brain is poorly understood. In this experimental study, the effects of HBO on BBB integrity were investigated in comparison with hyperbaric air (HBA) in intact rats. Four sessions of HBA or HBO were applied to intact rats in 24h. BBB integrity was functionally and structurally evaluated by determining extravasation of Evans blue (EB) dye and horseradish peroxidase (HRP) tracers. In immunohistochemical evaluation, relative staining intensity for occludin, a tight junction (TJ) protein, and aquaporin 4 (AQP4), a water-channel protein, was detected in the barrier type of microvessels of brain by image analysis. BBB permeability to EB dye significantly increased in animals in HBO treatment group compared to those in HBA and control groups (p<0.05). The immunoreactivity of occludin, a tight junction protein, remained essentially unaltered in capillaries of hippocampus in all groups. In animals exposed to HBO, AQP4 immunoreactivity significantly increased in parietal cortex compared to those in HBA and control groups (p<0.01). Ultrastructurally, frequent vesicles containing HRP reaction products were observed in capillary endothelial cells in cerebral cortex and hippocampus of rats subjected to both HBA and HBO. Our results indicate that the HBO administration to intact rats increased BBB permeability to both EB and HRP while HBA increased only HRP extravasation in these animals. The results of this study suggest that HBA also impairs the BBB integrity in intact rats as well as HBO.

Response of Rat Erythrocyte Oxidative Stress Markers to Repetitive Hyperbaric Oxygen Exposures Up to 40 Daily Sessions / Odgovor Markera Oksidativnog Stresa U Eritrocitima Pacova Na Višestruko Izlaganje Hiperbaričnom Kiseoniku Do 40 Seansi Dnevno

Summary Background: Studies with single-session hyperbaric oxygen exposures have shown that HBO-induced oxidative stress is proportional to exposure pressure and duration. Since the efficacy of hyperbaric oxygen mainly depends on repetitive exposures, this study aimed to investigate the oxidative effect of hyperbaric oxygen administered for 5 to 40 sessions. Methods: Sixty rats were divided into one control and 6 study groups. Study groups were exposed to 5, 10, 15, 20, 30, and 40 daily consecutive 2.8 atm/90 min hyperbaric oxygen sessions. Animals were sacrificed 24 h after the last hyperbaric oxygen administration. Malondialdehyde and carbonylated protein levels as well as superoxide dismutase activities were determined in isolated rat erythrocytes. Results: Carbonylated protein levels increased significantly after just 5 hyperbaric oxygen exposures; reached a peak level with 10 exposures; were still significantly higher than controls after 15 sessions; and decreased to normal limits after 20 exposures. Malondialdehyde levels were found to be significantly increased in the 10 to 30, but not in the 5 and 40-session groups. Superoxide dismutase activity showed elevated levels only in the 5 and 10 times hyperbarical oxygen-exposed groups. Conclusions: The suppressed oxidative stress level after 40 exposures suggests an effective endogenous antioxidant defense in repetitive HBO administrations.

Does Hyperbaric Oxygen Administration Before or After Irradiation Decrease Side Effects of Irradiation on Implant Sites?

One of the main limitations of implant-based breast reconstruction is the high rate of complications such as capsular contracture and poor aesthetic outcome, due to adjuvant radiotherapy. Hyperbaric oxygen treatment (HBOT) has been used to assist wound healing in the prevention and treatment of the side effects of irradiation. We aimed to investigate this effect of HBOT on the capsule reaction and skin, applied before and after irradiation, following the placement of an implant under the dorsal skin of the rat. Fifteen Wistar rats were randomly divided into 3 groups. A 18-mL smooth testicular implant was introduced into a subcutaneous pocket located on the dorsum of each rat. A single dose of 17-Gy irradiation was given to the implanted area of each rat at the third week. HBOT which lasted 3 weeks was administered to group I before irradiation, group II after irradiation. The control group did not receive HBOT. All of the rats were killed at the ninth week (6 weeks after irradiation). The dorsal skin with the capsule overlying the implant were excised for histopathological processing. The thickness of the capsule reaction of each group was evaluated statistically. Our histopathological examination revealed changes due to radiation in the control group. Many of these findings were found to be more subtle in group I and nearly absent in the group II. There was not any statistical difference between the thickness of the capsule reactions of the control group and group I, or group I and group II, but the capsular thickness of the control group was statistically higher than group II. It can be predicted that the use of HBOT following irradiation is an effective tool to reduce the capsule reaction of the implanted area and the tissue damage seen in radiodermatitis.

Hyperbaric oxygen for carbon monoxide poisoning

Poisoning with carbon monoxide (CO) remains an important cause of accidental and intentional injury worldwide. Several unblinded non-randomized trials have suggested that the use of hyperbaric oxygen (HBO) prevents the development of neurological sequelae. This has led to the widespread use of HBO in the management of patients with carbon monoxide poisoning. To examine randomised trials of the efficacy of hyperbaric oxygen (HBO) compared to normobaric oxygen (NBO) for the prevention of neurologic sequelae in patients with acute carbon monoxide poisoning. We searched the following electronic databases; Cochrane Injuries Group Specialised Register (searched June 2010), Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 2), MEDLINE (Ovid SP) 1950 to June 2010, EMBASE (Ovid SP) 1980 to June 2010, ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) 1970 to June 2010, ISI Web of Science: Conference Proceedings Citation Index-Science (CPCI-S) 1990 to June 2010. All randomised controlled trials of HBO compared to NBO, involving non-pregnant adults who are acutely poisoned with carbon monoxide (regardless of severity). Two authors independently extracted from each trial information on: the number of randomised patients, types of participants, the dose and duration of the intervention, and the prevalence of neurologic symptoms at follow-up. Seven randomised controlled trials of varying quality were identified; one was excluded because it did not evaluate clinical outcomes. Of the six remaining trials involving 1361 participants, two found a beneficial effect of HBO for the reduction of neurologic sequelae at one month, while four others did not. One of these is an incomplete publication (an abstract of an interim analysis). Although pooled random effects meta-analysis does not suggest a significant benefit from HBOT (OR for neurological deficits 0.78, 95%CI 0.54 to 1.12), significant methodologic and statistical heterogeneity was apparent among the trials, and this result should be interpreted cautiously. Moreover, design or analysis flaws were evident in all trials. Importantly, the conclusions of one positive trial may have been influenced by failure to adjust for multiple hypothesis testing, while interpretation of the other positive trial is hampered by a high risk of bias introduced during the analysis including an apparent change in the primary outcome. Both were also stopped early 'for benefit', which is likely to have inflated the observed effect. In contrast three negative trials had low power to detect a benefit of HBO due to exclusion of severely poisoned patients in two and very poor follow-up in the other. One trial that was said to be finished around eight years ago has not reported the final analysis in any forum. Existing randomised trials do not establish whether the administration of HBO to patients with carbon monoxide poisoning reduces the incidence of adverse neurologic outcomes. Additional research is needed to better define the role, if any, of HBO in the treatment of patients with carbon monoxide poisoning. This research question is ideally suited to a multi-center randomised controlled trial.

QUALITY OF LIFE AMONG THE PATIENTS WITH CARDIOVASCULAR DISEASE ISCHEMICAL GENESIS AT THE ADMINISTRATION OF THE HYPERBARIC OXYGENATION IN «LITTLE» REGIMES IN THE 2-YEARS INVESTIGATORS

Administration of hyperbaric oxygenation in the treatment of cardiovascular disease ischemical genesis indicate high efficacy and statistical reliable improvement integral score of physical component of health (47,7 ± 1,2 in test group, 41,1 ± 0,5 points in control group) and mental component of health (51,6 ± 1,1 in test group, 45,2 ± 0,2 in control group) in the patients in the 2-years observation (p < 0,01), it high correlate do decrease survive patients in the test group.

Osteoradionecrosis of the jaws—a current overview—part 2: dental management and therapeutic options for treatment

The aim of this paper is to explore the current theories about pretreatment assessment and dental management of patients receiving head and neck radiotherapy, and the therapeutic options to treat osteoradionecrosis of the jaws, based on the literature review. Osteoradionecrosis is one of the most serious oral complications of head and neck cancer treatment. Osteoradionecrosis is a severe delayed radiation-induced injury, characterized by bone tissue necrosis and failure to heal. Osteoradionecrosis either stabilizes or gradually worsens and is notoriously difficult to manage. Because most cases occur in patients who were dentulous in the mandible at tumor onset, proper dental management is the single most important factor in prevention. Complete dental clearance before treatment is no longer necessary. Controversy exists regarding the management of osteoradionecrosis of the maxillofacial skeleton because of the variability of this condition. The treatment of osteoradionecrosis has included local wound care, antibiotic therapy, surgical procedures, and the administration of hyperbaric oxygenation. Recently, new methods of treatment were introduced, according to the new theory about its pathophysiology.

Human Amniotic Fluid Mesenchymal Stem Cells in Combination with Hyperbaric Oxygen Augment Peripheral Nerve Regeneration

Attenuation of pro-inflammatory cytokines and associated inflammatory cell deposits rescues human amniotic fluid mesenchymal stem cells (AFS) from apoptosis. Hyperbaric oxygen (HBO) suppressed stimulus-induced pro-inflammatory cytokine production in blood-derived monocyte-macrophages. Herein, we evaluate the beneficial effect of hyperbaric oxygen on transplanted AFS in a sciatic nerve injury model. Peripheral nerve injury was produced in Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The AFS were embedded in fibrin glue and delivered to the injured site. Hyperbaric oxygen (100% oxygen, 2 ATA, 60 min/day) was administered 12 h after operation for seven consecutive days. Transplanted cell apoptosis, oxidative stress, inflammatory cell deposits and associated chemokines, pro-inflammatory cytokines, motor function, and nerve regeneration were evaluated 7 and 28 days after injury. Crush injury induced an inflammatory response, disrupted nerve integrity, and impaired nerve function in the sciatic nerve. However, crush injury-provoked inflammatory cytokines, deposits of inflammatory cytokines, and associated macrophage migration chemokines were attenuated in groups receiving hyperbaric oxygen but not in the AFS-only group. No significant increase in oxidative stress was observed after administration of HBO. In transplanted AFS, marked apoptosis was detected and this event was reduced by HBO treatment. Increased nerve myelination and improved motor function were observed in AFS-transplant, HBO-administrated, and AFS/HBO-combined treatment groups. Significantly, the AFS/HBO combined treatment showed the most beneficial effect. AFS in combination with HBO augment peripheral nerve regeneration, which may involve the suppression of apoptotic death in implanted AFS and the attenuation of an inflammatory response detrimental to peripheral nerve regeneration.

Early complications following haematopoietic SCT in children

Early complications can be defined as those occurring within 100 days after transplant. Both epithelial and endothelial damage represent the pathogenetic basis for the onset of the most frequent complications. Clinical features related to endothelial damage depend on the involved district or on the grade and type of general distribution. Veno-occlusive disease (VOD) most often occurs within the first 20 days of haematopoietic SCT (HSCT) and is characterized by the obstruction of small intrahepatic venules and is caused by an initial injury of the sinusoid endothelial cells. The incidence in children ranges between 27 and 40%, and symptoms include hepatomegaly, portal hypertension and ascites. Early intervention with defibrotide (DF) proved to be effective for the treatment; however, overall mortality ranges between 20 and 50%. Thrombotic microangiopathy (TAM) incidence is 4-13%. It is often associated with the use of CYA or tacrolimus, and symptoms include haemolytic anaemia, thrombocytopenia and renal and/or central nervous system impairment. Treatment includes plasmapheresis and supportive care. The promising role of DF needs to be confirmed. The onset of engraftment syndrome may occur 1 or 2 days before the neutrophil count in peripheral blood increases. Clinical symptoms include fever not related to infection, respiratory involvement with pulmonary infiltrates or hypoxia and skin rash. Treatment consists of steroid administration for a few days. Haemorrhagic cystitis (HC) may occur early or later following transplant. Early-onset HC is related to mucosal damage caused by the catabolites of chemotherapy drugs, and late-onset HC is mostly caused by viral infections. The incidence ranges between 1 and 25%. Clinical symptoms include haematuria and dysuria without infections. Treatment includes hyperhydration and platelet support. In case of vescical clots, bladder irrigation is indicated. In advanced cases, hyperbaric oxygen administration or surgery may be useful. The use of cidofovir for BK virus-related HC seems encouraging, but further studies are needed to confirm its real efficacy.

Effects of Methylprednisolone and Hyperbaric Oxygen on Oxidative Status after Experimental Spinal Cord Injury: A Comparative Study in Rats

The effects of hyperbaric oxygen (HBO) therapy or methylprednisolone on the oxidative status were evaluated in experimental spinal cord injury. Clip compression method was used to produce acute spinal cord injury rats. Hyperbaric oxygen was administered twice daily for a total of eight 90 min-sessions at 2.8 atmospheres. Methylprednisolone was first injected with a bolus of 30 mg/kg followed with an infusion rate of 5.4 mg/kg/h for 24 h. Five days after clip application animals were sacrificed and their traumatized spinal cord segment were excised. Tissue levels of thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were evaluated to reflect oxidant/antioxidant status. Non-treated clip-operated animals reflected significantly higher SOD, GSH-Px and TBARS levels that were found to be significantly higher than the sham-operated. Methylprednisolone was not able to lower these levels. HBO administration diminished all measured parameters significantly; however, their levels appeared already to be high when compared with sham animals. According to these results obtained on the 5th day after induction, HBO, but not methylprednisolone, seems to procure prevention against oxidative spinal cord injury.

Osteonecrosis of the jaws due to bisphosphonate use. A review of 60 cases and treatment proposals

Purpose Bisphosphonates are compounds used in the treatment of various metabolic and malignant bone diseases. In the last two and a half years, there has been a striking increased referral of patients with exposed necrotic jawbone, mostly after several teeth extractions. The only clinical feature common in all patients was the use of bisphosphonates in the treatment of bone diseases. Patients and methods We performed a retrospective multicentric study of 60 patients with necrotic bone lesions of the jaws of various extent from July 2003 to October 2005. The necrotic bone involved the maxilla (37%), the mandible (50%), or both (13%). The bisphosphonate administered was mostly zoledronate. The management of the patients included cessation of bisphosphonate therapy for more than 6 months, long-term antibiotics, hyperbaric oxygen administration in some cases, and various surgical restorative procedures. Results The implementation of the treatment protocol in 7 patients so far lead to high cure rates, whereas surgical restoration of the defect without previous cessation of bisphosphonate therapy had discouraging results. Conclusions Clinicians and dentists should have in mind this new complication of bisphosphonate administration to identify and treat osteonecrosis of the jaws.

Effects of hyperbaric oxygen on gene expressions of procollagen, matrix metalloproteinase and tissue inhibitor of metalloproteinase in injured medial collateral ligament and anterior cruciate ligament

Animal experiments were performed to investigate whether and how the administration of hyperbaric oxygen (HBO) affects gene expressions of procollagens, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in injured medial collateral ligament (MCL) and anterior cruciate ligament (ACL). In 64 Sprague-Dawley rats, the MCL of the left knee was lacerated at the midsubstance, and the ACL of the left knee was lacerated adjacent to the tibial insertion in another 64 rats. Of these, 32 rats with lacerated MCL and 32 rats with lacerated ACL were housed in individual cages at normal atmospheric pressure (Groups MC and AC, respectively), while the remaining 64 rats were exposed to 100% oxygen at 2.5 atmospheres absolute for 2 h for 5 days a week (Groups MH and AH, respectively). Rats were sacrificed at 3, 7, 14 and 28 days postoperatively. After macroscopic examination, bilateral MCLs were harvested from Groups MC and MH, and bilateral ACLs from Groups AC and AH. Total RNA was extracted from each specimen and gene expressions of type I and type III procollagens, MMP-2, -9 and -3, and TIMP-1 and -2 were estimated using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Macroscopically, lacerated MCL healed by scar tissue formation, the amount of which appeared to be greater in Group MH than in Group MC. In contrast, no lacerated ACLs united, and little, if any, differences were apparent in macroscopic findings between Groups AH and AC. Gene expression of type I procollagen was significantly greater in Group MH than in Group MC at 7 days postoperatively and was also significantly greater in Group AH than in Group AC at 28 days (P<0.05). No significant differences in type III procollagen gene expression were noted between Groups MH and MC or between Groups AH and AC. In addition, no significant differences in gene expressions of MMPs were seen in either ligament, except that gene expression of MMP-13 was significantly lower at 7 days in Group MH than in Group MC (P<0.05). Gene expressions of TIMPs did not differ significantly between Groups MH and MC in each time interval, whereas gene expressions of TIMPs were significantly greater in Group AH than in Group AC at 7, 14 and 28 days for TIMP-1 and at 3, 7 and 14 days for TIMP-2 (P<0.05). RT-PCR results suggested that HBO enhances structural protein synthesis and inhibits degradative processes by enhancing TIMP activities in the lacerated ACL. However, none of the lacerated ACLs united macroscopically despite administration of HBO, indicating that the effect of HBO is insufficient for healing of the injured ACL. If HBO therapy is used as an adjunctive therapy after primary repair of the injured ACL, the success rate of surgery seems likely to be increased.

Negative Effect of Immediate Hyperbaric Oxygen Therapy in Acute Acoustic Trauma

The functional evaluation of the effect of the hyperbaric oxygen therapy (HBOT) onset time on cochlea by using distortion product otoacoustic emission. Animal study. Twenty-four Wistar albino rats were divided into six groups and their right ears were directly exposed to a 110-dB sound pressure level (1-12 kHz) white noise for 25 minutes. The first group was considered the control group. HBOT was started at 1 hour postexposure for the second group, at 2 hours postexposure for the third group, at 6 hours postexposure for the fourth group, at 24 hours postexposure for the fifth group, and at 48 hours postexposure for the sixth group. Signal-to-noise ratios (SNRs) were recorded before the noise exposure; immediately after the noise exposure; and on the 3rd, 7th, and 10th day of postexposure. SNRs at 6 to 8 kHz were significantly decreased after the acoustic trauma. The evaluation on the third day of postexposure showed that recovery begun in all groups except the group in which the HBOT was started at 1 hour postexposure. SNRs in the control group and HBOT groups were back to the preexposure levels at 10 days postexposure, except the 1- and 2-hour postexposure groups. However, in the group in which the HBOT was started at 1 hour postexposure, distortion product otoacoustic emissions were lost except at 4 kHz. The recovery of the SNRs in hyperbaric oxygen administration at 2 hours postexposure almost completed on the 10th day after noise exposure. Immediate HBOT in acoustic trauma treatment is not necessary; on the contrary, it has an adverse effect.