Exhaled breath condensate profiles of U.S. Navy divers following prolonged hyperbaric oxygen (HBO) and nitrogen-oxygen (Nitrox) chamber exposures.

Prolonged exposure to hyperbaric hyperoxia can lead to pulmonary oxygen toxicity (PO2tox). PO2tox is a mission limiting factor for special operations forces divers using closed-circuit rebreathing apparatus and a potential side effect for patients undergoing hyperbaric oxygen (HBO) treatment. In this study, we aim to determine if there is a specific breath profile of compounds in exhaled breath condensate (EBC) that is indicative of the early stages of pulmonary hyperoxic stress/PO2tox. Using a double-blind, randomized 'sham' controlled, cross-over design 14 U.S. Navy trained diver volunteers breathed two different gas mixtures at an ambient pressure of 2 ATA (33 fsw, 10 msw) for 6.5 h. One test gas consisted of 100% O2(HBO) and the other was a gas mixture containing 30.6% O2with the balance N2(Nitrox). The high O2stress dive (HBO) and low O2stress dive (Nitrox) were separated by at least seven days and were conducted dry and at rest inside a hyperbaric chamber. EBC samples were taken immediately before and after each dive and subsequently underwent a targeted and untargeted metabolomics analysis using liquid chromatography coupled to mass spectrometry (LC-MS). Following the HBO dive, 10 out of 14 subjects reported symptoms of the early stages of PO2tox and one subject terminated the dive early due to severe symptoms of PO2tox. No symptoms of PO2tox were reported following the nitrox dive. A partial least-squares discriminant analysis of the normalized (relative to pre-dive) untargeted data gave good classification abilities between the HBO and nitrox EBC with an AUC of 0.99 (±2%) and sensitivity and specificity of 0.93 (±10%) and 0.94 (±10%), respectively. The resulting classifications identified specific biomarkers that included human metabolites and lipids and their derivatives from different metabolic pathways that may explain metabolomic changes resulting from prolonged HBO exposure.

Protective mechanism of traditional Chinese medicine guizhi fuling pills against carbon tetrachloride-induced kidney damage is through inhibiting oxidative stress, inflammation and regulating the intestinal flora.

BACKGROUND: Chemical or drug-induced kidney damage has been recognized as a critical cause of kidney failure. The oxidative stress, inflammation, and imbalance of intestinal flora caused by carbon tetrachloride (CCl4) play a fundamental role in chronic kidney damage. Guizhi Fuling pills (GZFL) is a traditional formula consisting of five traditional Chinese medicinal herbs, which can promote blood circulation and improve kidney function. The underlying mechanisms of GZFL improving kidney damage are not fully understood yet. AIM: The current study aimed to explore the effects of GZFL on CCl4-induced kidney damage and intestinal microbiota in mice. METHODS: Male ICR mice were intraperitoneally administered with 20% CCl4 (mixed in a ratio of 1:4 in soybean oil) twice a week, for 4 weeks to induce kidney damage. Creatinine (CRE), urea nitrogen, antioxidant enzymes, and inflammatory cytokines were measured and the histology of the kidney, jejunum, and colon examination to assess kidney and intestinal damage. The expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2) family members, nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome in kidney tissues, and the tight junction proteins in colonic tissues were detected by Western blot. The gut microbiota was analyzed through 16S rRNA gene sequencing. RESULTS: GZFL treatment decreased the serum CRE and urea nitrogen levels. Moreover, GZFL reduced the levels of pro-inflammatory cytokines and increased antioxidant enzyme activities in kidney and colonic tissues. GZFL improved the kidney, jejunum, and colon histology. Furthermore, GZFL inhibited the expressions of NLRP3, ASC, and cleaved-Caspase-1, while Nrf2, HO-1, NQO1, GCLM, and tight junction proteins were increased. The dysbiosis of intestinal microbiota improved after GZFL treatment. CONCLUSIONS: This study showed that GZFL could improve kidney damage, which might be mainly via the integrated regulations of the Nrf2 pathway, NLRP3 inflammasome, and composition of intestinal microbiota.

Reconstruction using a frozen autograft for a skull and humeral lesion of synchronous multicentric osteosarcoma after undergoing successful neoadjuvant chemotherapy: a case report and review of the literature.

BACKGROUND: Synchronous multicentric osteosarcoma (SMOS) is a rare disease characterized by simultaneous multicentricity of intraosseous osteosarcoma without visceral involvement. SMOS, including a skull lesion, which occurs relatively rarely, and reconstruction using a frozen autograft after the excision of a lesion of SMOS has been infrequently reported previously. CASE PRESENTATION: We report an 18-year-old girl with SMOS, with lesions located in the left distal femur, right proximal humerus, and left occipital bone. Her major complaint was pain and swelling around the left knee joint. Asymptomatic lesions of the humerus and skull bone were detected on a systemic bone scan. No visceral organ metastasis was observed. A biopsy of the distal femoral lesion revealed osteosarcoma. Based on the histological findings, multiple bone lesions, and absence of visceral lesion, the clinical diagnosis of SMOS was made. After five courses of neoadjuvant chemotherapy with a regimen of doxorubicin and cisplatin, reconstruction using a tumor prosthesis following wide excision of the left distal femur was performed, and total necrosis was histologically observed in the retracted specimen. Following three cycles of adjuvant chemotherapy, tumor excision and reconstruction with a frozen autograft treated with liquid nitrogen was conducted for both lesions of the humerus and skull, rather than tumor prosthesis or synthetics, in order to retain a normal shoulder function, and to obtain a good cosmetic and functional outcome after treatment of the skull lesion. Further adjuvant chemotherapy could not be administered after the completion of the surgical treatment for all lesions because the adverse events due to chemotherapy were observed. At over 5 years after the diagnosis, she remains clinically disease-free. CONCLUSIONS: An early correct diagnosis, the proper management of chemotherapy, and surgical treatment for all lesions are essential for achieving a good clinical outcome, even in SMOS including a skull lesion. By performing reconstruction using a frozen autograft for a proximal humeral lesion and a skull lesion after confirming the good histological efficacy of neoadjuvant chemotherapy for the primary lesion, the excellent function of the shoulder joint and a good cosmetic outcome at the site of the skull lesion was acquired without complications or recurrence.

Nitrogen-bisphosphonate therapy is linked to compromised coenzyme Q10 and vitamin E status in postmenopausal women.

BACKGROUND: Nitrogen-bisphosphonates (N-BPs) are the most widely used drugs for bone fragility disorders. Long-term or high-dose N-BP use is associated with unusual serious side effects such as osteonecrosis of the jaw, musculoskeletal pain, and atypical fractures of long bones. It has escaped notice that the pathway N-BPs block is central for the endogenous synthesis of coenzyme Q10, an integral enzyme of the mitochondrial respiratory chain and an important lipid-soluble antioxidant. Our objective was to assess the coenzyme Q10 and antioxidant status in relation to N-BP exposure in women with postmenopausal osteoporosis. METHODS: Seventy-one postmenopausal women (age, 73.5 ± 5.5 y) with osteoporosis and no other malignancy were included in this cross-sectional study. Seventeen were treatment naive, 27 were on oral N-BP, and 27 were on i.v. N-BP. RESULTS: Vitamin E γ-tocopherol levels (µmol/mL) were significantly reduced in N-BP users [oral, H(2) = 18.5, P = .02; i.v., H(2) = 25.2, P < .001; mean rank comparisons after Kruskal-Wallis test). Length of time (days) of N-BP exposure, but not age, was inversely associated with the coenzyme Q10/cholesterol ratio (µmol/mol) (ß = -0.27; P = .025), which was particularly low for those on i.v. N-BP (mean difference = -35.0 ± 16.9; 95% confidence interval, -65.2 to -4.9; P = .02). CONCLUSION: The degree of N-BP exposure appears related to compromised coenzyme Q10 status and vitamin E γ-tocopherol levels in postmenopausal women with osteoporosis. This phenomenon may link to certain adverse N-BP-associated effects. Confirmation of this would suggest that therapeutic supplementation could prevent or reverse certain complications of long-term N-BP therapy for at-risk individuals.

Nitrogen plasma skin regeneration and aesthetic facial surgery: multicenter evaluation of concurrent treatment.

OBJECTIVE: To evaluate the safety and efficacy of aesthetic facial surgery with concurrent nitrogen plasma skin regeneration. METHODS: During a 28-month period, we independently completed 272 concurrent procedures in 95 patients aged 42 to 80 years in whom nitrogen plasma skin regeneration was performed immediately on completion of various aesthetic procedures, including brow-lift, blepharoplasty, lateral canthoplasty, midface-lift, rhytidectomy, cheek augmentation, lip vermillion advancement, filler injections, and augmentation mentoplasty. The treatment variables evaluated included nitrogen plasma pulse energy, pass number, and pulse count, and outcomes monitored included complications and subjective aesthetic improvement. RESULTS: The various treatment combinations were well tolerated at all anatomical sites. Rhytidectomy flap treatment included escalation of single-pass low-energy to high-energy nitrogen plasma treatment. Although perioperative complications did not otherwise negatively affect results, they included erythema with acneiform eruption (in 2 patients) and presumed herpes simplex virus infection, brief healing delay, and postinflammatory hyperpigmentation (in 1 patient each). In general, the treatment combinations were synergistic. CONCLUSIONS: Combining nitrogen plasma skin regeneration with aesthetic facial surgery enhances outcomes for procedures in the forehead and in the periorbital, midface, and perioral regions. It does not seem to increase the risk of dermatologic or surgical complications for the procedures described herein.

Guiding principles in choosing a therapeutic table for DCI hyperbaric therapy.

Hyperbaric therapy is the basis of treatment for pervasive development disorders. For this reason, the choice of the right therapeutic table for each case is critical. Above all, the delay in recompression time with respect to the first symptoms and to the severity of the case must be considered. In our experience, the use of low-pressure oxygen tables resolves almost all cases if recompression takes place within a short time. When recompression is possible almost immediately, the mechanical effect of reduction on bubble volume due to pressure is of remarkable importance. In these cases, high-pressure tables can be considered. These tables can also be used in severe spinal-cord decompression sickness. The preferred breathing mixture is still disputed. Heliox seems to be favored because it causes fewer problems during the recompression of divers, and above all, because nitrox can cause narcosis and contributes nitrogen. Saturation treatment should be avoided or at least used only in special cases. In cases of arterial gas embolism cerebral injury, it is recommended to start with an initial 6 ATA recompression only if the time between symptom onset and the beginning of recompression is less than a few hours.

Combined effect of denucleation and denitrogenation on the risk of decompression sickness in rats.

We previously hypothesized that the number of bubbles emerging on decompression from a dive, and the resultant risk of decompression sickness (DCS), may be reduced by a process whereby effective gas micronuclei that might otherwise have formed bubbles on decompression are shrunk and eliminated. In a procedure defined by us as denucleation, exposure to hyperbaric oxygen (HBO) would result in oxygen replacing the resident gas in the micronuclei, to be subsequently consumed by the mitochondria when the oxygen pressure is reduced. Support for the validity of our hypothesis may be found in our previous studies on the transparent prawn and the reduction of DCS in the rat. In all of these studies, HBO pretreatment was given before supersaturation with inert gas at high pressure. The purpose of the present study was to compare DCS outcome in rats that underwent nitrogen washout (denitrogenation) alone (9 min O(2) at 507 kPa) after exposure to air at high pressure (33 min at 1,266 kPa), and rats treated by both procedures (denitrogenation + denucleation; 8 min of O(2) breathing followed by 5 min air breathing, both at 507 kPa) after high-pressure air exposure. This was done with the same nitrogen load in both groups before the final decompression (a nitrogen pressure of 467 kPa in fatty and 488 kPa in aqueous tissue). Six of 20 rats in the denitrogenation + denucleation group died, compared with 13 in the denitrogenation group (P < 0.03). Three rats in the denitrogenation + denucleation group suffered mild DCS, recovering completely within 2 h of decompression. The present study indicates an advantage in considering both denitrogenation and denucleation before decompression. This may have practical application before escape from a disabled submarine, when aborting a technical dive, or in the preparation of aviators for high altitude.

The cyclooxygenase-2 inhibitor GW406381X [2-(4-ethoxyphenyl)-3-[4-(methylsulfonyl)phenyl]-pyrazolo[1,5-b]pyridazine] is effective in animal models of neuropathic pain and central sensitization.

The pathogenic form of the cyclooxygenase (COX) enzyme, COX-2, is also constitutively present in the spinal cord and has been implicated in chronic pain states in rat and man. A number of COX-2 inhibitors, including celecoxib and rofecoxib, are already used in man for the treatment of inflammatory pain. Preclinically, the dual-acting COX-2 inhibitor, GW406381X [2-(4-ethoxyphenyl)-3-[4-(methylsulfonyl)phenyl]-pyrazolo[1,5-b]pyridazine, where X denotes the free base], is as effective as rofecoxib and celecoxib in the rat established Freund's Complete Adjuvant model with an ED(50) of 1.5 mg/kg p.o. compared with 1.0 mg/kg p.o. for rofecoxib and 6.6 mg/kg p.o. for celecoxib. However, in contrast to celecoxib (5 mg/kg p.o. b.i.d.) and rofecoxib (5 mg/kg p.o. b.i.d.), which were without significant effect, GW406381X (5 mg/kg p.o. b.i.d.) fully reversed mechanical allodynia in the chronic constriction injury model and reversed thermal hyperalgesia in the mouse partial ligation model, both models of neuropathic pain. GW406381X, was also effective in a rat model of capsaicin-induced central sensitization, when given intrathecally (ED(50) = 0.07 mug) and after chronic but not acute oral dosing. Celecoxib and rofecoxib had no effect in this model. Several hypotheses have been proposed to try to explain these differences in efficacy, including central nervous system penetration, enzyme kinetics, and potency. The novel finding of effectiveness of GW406381X in these models of neuropathic pain/central sensitization, in addition to activity in inflammatory pain models and together with its central efficacy, suggests dual activity of GW406381X compared with celecoxib and rofecoxib, which may translate into greater efficacy in a broader spectrum of pain states in the clinic.

How to feed patients with renal dysfunction.

Renal dysfunction is common in critically ill patients and its presence has, in the past, posed serious challenges to nutritional support. Such challenges were due to the increased azotemia induced by protein or amino acid administration, the fluid overload caused by the administration of nutrients and the difficulties associated with the control of these complications by means of conventional dialytic techniques. The development and increasing application of continuous renal replacement therapy (CRRT) has removed such concerns, because control of azotemia and fluid balance can be predictably and reliably achieved in all patients. Accordingly, the presence of renal failure should in no way influence the amount or type of nutritional support administered to a critically ill patient. We recommend that approximately 30-35 kcal/kg/day be administered enterally and begun within the first few hours of admission to the intensive care unit and that protein intake be kept in the 1.5-2 g/kg/day range. Accumulating evidence also suggests that immune-enhancing enteral preparations decrease the duration of hospital stay, the number of infections and perhaps mortality. Such preparations should be used in these patients. Finally adequate vitamin and trace element supplementation is recommended to counterbalance the decrease in antioxidants and the loss of some vitamins during CRRT. Available evidence suggests that if these steps are applied as part of a protocol-based approach to the nutritional support of patients with renal failure, their morbidity and perhaps mortality can be significantly decreased.

[The effect of measured hypoxia on the development of situational osteopenia]. / Vplyv dozovanoï hipoksiï na rozvytok sytuatsiinoï osteopeniï.

The influence of gas mixture with low PO2 (90-110 mm Hg) on calcium-phosphorus metabolism and biomechanical properties of femur bones at rats, who were kept under condition of hind-limb unloading during 28-days, has been studied. Loss of calcium and phosphorus during a day was less in rats, who was received gas mixture with lower PO2, than rats who was kept in condition of hind-limb unloading only. Hypoxic gas mixture stabilized mechanical properties of bones tissue in femoral bone of rats. Gas mixture with lower pressure of oxygen retard development of osteopenia and may be used with other corrective methods for situation osteopenia prevention.

[The effect of nitrogen silicide thermal mineral water on stomach function in gastroduodenal pathology]. / Vliianie azotno-kremnistoi ternmal'noi mineral'noi vody na funktsional'noe sostoianie zheludka pri gastroduodenal'noi patologii.

Patients with ulcer, hyperacid and normal acid gastritis were given nitrogen silicate mineral water from Annensk thermal springs. The water was found to inhibit acid-pepsin-forming function and to improve gastric motility and evacuation. Acceptable fluoride concentration and not a single case of the disease aggravation make the above mineral water suitable for rehabilitation of patients with ulcer and gastritis.

[The hypolipidemic action of water-soluble enterosorbents of cholesterol and bile acids in an experiment]. / Gipolipidemicheskoe deistvie vodorastvorimykh énterosorbentov kholesterina i zhelchnykh kislot v éksperimente.

Experiments on rats, guinea pigs and rabbits with experimental dyslipoproteinemia have revealed that the new water-soluble high-molecular weight polymers containing digitonin (ED) or a quaternary nitrogen atom (EA) have a more marked hypolipidemic action than cholestyramine and normalize lipoprotein metabolism. The digitonin-containing enterosorbent has been shown to decrease the absorption of 4-14C-cholesterol, while the nitrogen-containing enterosorbent diminishes the absorption of 3H-cholic acid.

[Enhancement of the radioprotective action of gas-induced hypoxia by using dextran sulfate]. / Usilenie radiozashchitnogo deistviia gazovoi gipoksii dekstransul'fatom.

Mice of the strain (CBA X C57Bl) F1 injected with a single dose (40 mg.kg-1) of dextran sulphate (m.w. 5 X 10(5] were used to determine the survival rate after a lethal dose (13.0 Gy) of gamma irradiation, the number of haemopoietic stem cells in bone marrow (CFUs) and that of spleen endogenous colonies. Irradiation was performed in a hypobaric chamber at levels of 20%, 15%, 12% and 10% of the oxygen content. While in the control groups the levels of hypoxia showed a weak radioprotective effect in animals treated with DS, radioprotection was observed both in 10% O2 and in 15% O2. The animals treated exhibited a higher survival rate up to day 30 after irradiation, an elevated number of survived haemopoietic stem cells (CFUs) in the bone marrow, and increased number of endogenous spleen colonies, as compared with the control group. The potentiation of the radioprotective effect of hypoxia (10% O2) was observed till the end of observation (6th day after DS injection). The results obtained support an earlier observation that increased activity of haemopoiesis forms a convenient pool for the potentiation of the radioprotective efficiency of hypoxic hypoxia.

[Radiosensitivity during the irradiation of animals in an altered gaseous environment. A comparative study on mice and rats of the radiation-protective effect of oxygen-deficient gas mixtures]. / Radiochuvstvitel'nost' pri obluchenii zhivotnykh v izmenennoi gazovoi srede. Sravnitel'noe issledovanie na myshakh i krysakh protivoluchevogo éffekta kisloroddefitsitnykh gazovykh smesei.

The radioprotective effect of gas hypoxic mixtures containing 5, 7, 8, 10 and 15% of oxygen on mice and rats was comparatively studied. The dependence of DMF upon oxygen concentration in the mixture was approximated by a hyperbolic function similar to the dependence of the radiomodifying effect of circulatory hypoxia caused by radioprotective agents of the indolylalkylamine series.

Delayed cerebral edema complicating cerebral arterial gas embolism: case histories.

A disquieting and rarely described feature of the treatment of arterial gas embolism (AGE) is the high incidence of relapse following good to excellent initial responses to recompression therapy. This paper includes a discussion of the issues involved in the etiology and clinical approach to the specific problem of relapse and relates experience from selected clinical cases to a modified therapeutic approach that has been introduced into Royal Navy diving and submarine medicine practice. It illustrates how and why current treatment procedures have been expressly designed to minimize the incidence of relapse and to modify favorably the pathophysiological responses (particularly vasogenic cerebral edema) associated with cerebral AGE.