CYBERMED LIFE - ORGANIC  & NATURAL LIVING

Cybermedlife - Therapeutic Actions Oxygen Therapy

A metaanalysis of the effectiveness and safety of ozone treatments for herniated lumbar discs.

Abstract Title: A metaanalysis of the effectiveness and safety of ozone treatments for herniated lumbar discs. Abstract Source: J Vasc Interv Radiol. 2010 Apr;21(4):534-48. Epub 2010 Feb 25. PMID: 20188591 Abstract Author(s): Jim Steppan, Thomas Meaders, Mario Muto, Kieran J Murphy Article Affiliation: ActiveO, Salt Lake City, Utah, USA. Abstract: PURPOSE: To determine statistically significant effects of oxygen/ozone treatment of herniated discs with respect to pain, function, and complication rate. MATERIALS AND METHODS: Random-effects metaanalyses were used to estimate outcomes for oxygen/ozone treatment of herniated discs. A literature search provided relevant studies that were weighted by a study quality score. Separate metaanalyses were performed for visual analog scale (VAS), Oswestry Disability Index (ODI), and modified MacNab outcome scales, as well as for complication rate. Institutional review board approval was not required for this retrospective analysis. RESULTS: Twelve studies were included in the metaanalyses. The inclusion/exclusion criteria, patient demographics, clinical trial rankings, treatment procedures, outcome measures, and complications are summarized. Metaanalyses were performed on the oxygen/ozone treatment results for almost 8,000 patients from multiple centers. The mean improvement was 3.9 for VAS and 25.7 for ODI. The likelihood of showing improvement on the modified MacNab scale was 79.7%. The means for the VAS and ODI outcomes are well above the minimum clinically important difference and the minimum (significant) detectable change. The likelihood of complications was 0.064%. CONCLUSIONS: Oxygen/ozone treatment of herniated discs is an effective and extremely safe procedure. The estimated improvement in pain and function is impressive in view of the broad inclusion criteria, which included patients ranging in age from 13 to 94 years with all types of disc herniations. Pain and function outcomes are similar to the outcomes for lumbar discs treated with surgical discectomy, but the complication rate is much lower (<0.1%) and the recovery time is significantly shorter. Article Published Date : Apr 01, 2010

Hyper- or normobaric oxygen therapy to treat migraine and cluster headache pain. Cochrane review

Abstract Title: [Hyper- or normobaric oxygen therapy to treat migraine and cluster headache pain. Cochrane review]. Abstract Source: Schmerz. 2008 Apr;22(2):129-32, 134-6. PMID: 17885769 Abstract Author(s): A Schnabel, M Bennet, F Schuster, N Roewer, P Kranke Article Affiliation: Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Universitätsklinikum Münster, Münster, Germany. Abstract: BACKGROUND: The aim of this systematic review was to assess the benefits and harms of supplemental oxygen (HBOT/NBOT) for treating and preventing migraine and cluster headaches. MATERIAL AND METHODS: All randomized trials comparing the effect of supplemental oxygen on migraine or cluster headache with those that exclude supplemental oxygen were included in this review. The systematic search included all relevant sources according to the paradigms of the Cochrane Collaboration. Data were analyzed with RevMan 4.2. RESULTS: Nine trials involving 201 participants satisfied the inclusion criteria. HBOT was effective in relieving an acute migraine and seemed to be sufficient in the treatment of an acute cluster attack. NBOT was effective in terminating acute cluster headache compared to sham treatment, but not in comparison to sublingual ergotamine. There was no evidence for any prophylactic effects. Serious adverse effects were not noted in the trials investigated. CONCLUSIONS: There is some evidence that HBOT is effective for termination of acute migraine. NBOT was similarly effective in cluster headache, however with sparse data. Because of costs and poor availability HBOT cannot be regarded as a routine therapy. Further indications in the case of treatment failure using standard therapy need to be defined based on data of future clinical trials. Article Published Date : Apr 01, 2008

Two cases of hepatopulmonary syndrome with improved liver function following long-term oxygen therapy.

Abstract Title: Two cases of hepatopulmonary syndrome with improved liver function following long-term oxygen therapy. Abstract Source: J Gastroenterol. 2007 Feb;42(2):176-80. Epub 2007 Mar 12. PMID: 17351808 Abstract Author(s): Kazuko Y Fukushima, Hiroshi Yatsuhashi, Akitoshi Kinoshita, Toshihito Ueki, Takehiro Matsumoto, Mitsuhiko Osumi, Yohjiro Matsuoka Abstract: Hepatopulmonary syndrome (HPS) is a complication of liver disease that is characterized by hypoxemia and intrapulmonary vascular dilatations. The only established therapy for this disorder is liver transplantation. Here, we report two patients (a 63-year-old woman and a 72-year-old man) with HPS associated with hepatitis C virus-related cirrhosis. We gave the patients low-dose oxygen supplementation to improve their respiratory symptoms. Surprisingly, their liver function improved from Child Pugh class C to class A, and ascites disappeared after a year of oxygen supplementation. We believe that long-term oxygen therapy contributed to the improvement of liver function in these two cases. Long-term oxygen therapy might offer a new therapeutic approach to improve liver function in patients with cirrhosis with hypoxemia. Article Published Date : Feb 01, 2007
Therapeutic Actions Oxygen Therapy

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Prevalence and Factors Contributing to Daytime and Nocturnal Hypoxemia in Chronic Heart Failure Patients.

Related Articles Prevalence and Factors Contributing to Daytime and Nocturnal Hypoxemia in Chronic Heart Failure Patients. Respiration. 2019 Jan 17;:1-10 Authors: Tamisier R, Bocquillon V, Treptow E, Destors M, Salvat M, Borrel E, Pépin JL Abstract BACKGROUND: Despite clinical optimization, many chronic heart failure (CHF) patients remain symptomatic with dyspnea and poor quality of life. STUDY OBJECTIVE: While oxygen therapy is prescribed in severe cases, the actual prevalence of different patterns of hypoxemia is unknown. METHODS: We analyzed 183 stable CHF patients with optimized medical treatment in the "MARS" database. The patients underwent cardiorespiratory sleep recording and complete daytime pulmonary function tests including arterial blood gases. RESULTS: This prospective cohort was predominately male (86.3%) with a mean age of 67.3 years (59.3; 75.7) and a mean BMI of 26.7 kg/m2 (23.7; 31.1). The patients were mainly in NYHA classes II and III with a mean left ventricular ejection fraction of 38%. 102 (55.61%) patients had ischemic cardiomyopathy with multiple comorbidities, and 64 (35.06%) had airflow obstruction. 8 (4.37%) patients had hypoxemia both day and night, and 151 (82.5%) had nocturnal hypoxemia only. All but 3 patients had sleep-disordered breathing (SDB), and either obstructive (59%) or central sleep apnea (39%) with a mean apnea-hypopnea index of 29.59/h (16.48; 48.27), an oxygen desaturation index of 27.09/h (14.09; 45.25), time below 90% saturation of 18 min (2; 64), and a mean nocturnal saturation of 93% (92; 94). Univariate analysis found nocturnal hypoxemia was associated with higher BMI and NT-proBNP levels. In multivariate analysis, only sleep apnea severity (p < 0.0001) and diurnal PaO2 remained significant. CONCLUSION: Most stable CHF patients suffer from nocturnal hypoxemia, while daytime hypoxemia is relatively rare. The degree of nocturnal hypoxemia depends on the severity of SDB. Hypoxemia phenotyping and severity could help better evaluate the need for appropriate therapy in CHF patients. PMID: 30654381 [PubMed - as supplied by publisher]

PEGylated mesoporous Bi2S3 Nanostars loaded with Chlorin e6 and doxorubicin for fluorescence/CT imaging-guided multimodal therapy of Cancer.

Related Articles PEGylated mesoporous Bi2S3 Nanostars loaded with Chlorin e6 and doxorubicin for fluorescence/CT imaging-guided multimodal therapy of Cancer. Nanomedicine. 2019 Jan 14;: Authors: Sun L, Hou M, Zhang L, Qian D, Yang Q, Xu Z, Kang Y, Xue P Abstract Taking advantage of the mesoporous structure of bismuth sulfide nanostars (Bi2S3 NSs), a chemotherapeutic drug of doxorubicin (DOX) and a photosensitizer of chlorin e6 (Ce6) were concurrently loaded in the PEGylated Bi2S3 NSs to formulate a multifunctional nanocomplex (BPDC NSs) for tumor theranostics. BPDC NSs have excellent photothermal conversion efficiency and a capacity of yielding reactive oxygen species (ROS) upon laser irradiation, and can realize on-demand drug release by either pH-activation or thermal induction. Accumulation of the nanodrug could be monitored in real-time by infrared thermal imaging, fluorescence imaging and computed tomography (CT). More importantly, the combination effects of photothermal therapy (PTT), photodynamic therapy (PDT) and chemotherapy was demonstrated to dramatically suppress solid tumors without recurrence in vivo. Featured by the low systemic toxicity and high biocompatibility, this nanoplatform could be a promising derivative of Bi2S3 NSs for imaging-guided theranostics of cancer. PMID: 30654184 [PubMed - as supplied by publisher]

Mesenchymal stem cell-derived extracellular vesicles and retinal ischemia-reperfusion.

Related Articles Mesenchymal stem cell-derived extracellular vesicles and retinal ischemia-reperfusion. Biomaterials. 2019 Jan 09;197:146-160 Authors: Mathew B, Ravindran S, Liu X, Torres L, Chennakesavalu M, Huang CC, Feng L, Zelka R, Lopez J, Sharma M, Roth S Abstract Retinal ischemia is a major cause of vision loss and impairment and a common underlying mechanism associated with diseases such as glaucoma, diabetic retinopathy, and central retinal artery occlusion. The regenerative capacity of the diseased human retina is limited. Our previous studies have shown the neuroprotective effects of intravitreal injection of mesenchymal stem cells (MSC) and MSC-conditioned medium in retinal ischemia in rats. Based upon the hypothesis that the neuroprotective effects of MSCs and conditioned medium are largely mediated by extracellular vesicles (EVs), MSC derived EVs were tested in an in-vitro oxygen-glucose deprivation (OGD) model of retinal ischemia. Treatment of R28 retinal cells with MSC-derived EVs significantly reduced cell death and attenuated loss of cell proliferation. Mechanistic studies on the mode of EV endocytosis by retinal cells were performed in vitro. EV endocytosis was dose- and temperature-dependent, saturable, and occurred via cell surface heparin sulfate proteoglycans mediated by the caveolar endocytic pathway. The administration of MSC-EVs into the vitreous humor 24 h after retinal ischemia in a rat model significantly enhanced functional recovery, and decreased neuro-inflammation and apoptosis. EVs were taken up by retinal neurons, retinal ganglion cells, and microglia. They were present in the vitreous humor for four weeks after intravitreal administration, with saturable binding to vitreous humor components. Overall, this study highlights the potential of MSC-EV as biomaterials for neuroprotective and regenerative therapy in retinal disorders. PMID: 30654160 [PubMed - as supplied by publisher]

Glucocorticoid-mediated effects on angiogenesis in solid tumors.

Related Articles Glucocorticoid-mediated effects on angiogenesis in solid tumors. J Steroid Biochem Mol Biol. 2019 Jan 14;: Authors: Martens B, Drebert Z Abstract Angiogenesis is essential in tumor development to maintain the oxygen and nutrient supply. Glucocorticoids have shown both direct and indirect angiostatic properties in various types of solid cancers. In most of the reported cases glucocorticoid-mediated actions involved suppression of multiple pro-angiogenic factors expression by cancer cells. The anti-angiogenic properties of glucocorticoids correlated with diminished tumor vasculature and reduced tumor growth in multiple in vivo studies. However, when glucocorticoid treatment is considered, possible adverse events should be taken into account. Additional research is needed to further test the use of these steroidal drugs in cancer therapy. PMID: 30654109 [PubMed - as supplied by publisher]

Carbon monoxide poisoning in Denmark with focus on mortality and factors contributing to mortality.

Related Articles Carbon monoxide poisoning in Denmark with focus on mortality and factors contributing to mortality. PLoS One. 2019;14(1):e0210767 Authors: Simonsen C, Thorsteinsson K, Mortensen RN, Torp-Pedersen C, Kjærgaard B, Andreasen JJ Abstract INTRODUCTION: Carbon monoxide (CO) poisoning is frequent worldwide but knowledge regarding the epidemiology is insufficient. The aim of this study was to clarify the extent of this intoxication, its mortality and factors associated with mortality. MATERIALS AND METHODS: National databases from Statistics Denmark were used to identify individuals who suffered from CO-poisoning during 1995-2015, as well as information regarding co-morbidities, mortality and manner of death. RESULTS: During the period from 1995 to 2015, 22,930 patients suffered from CO-poisoning in Denmark, and 21,138 of these patients (92%) were hospitalized. A total of 2,102 patients died within the first 30 days after poisoning (9.2%). Among these, 1,792 (85% of 2,102) were declared dead at the scene and 310 (15% of 2,102) died during hospitalization. Deaths due to CO-poisoning from smoke were intentional in 6.3% of cases, whereas deaths due to CO containing gases were intentional in 98.0% of cases. Among patients who survived >30 days, there was no significant difference in survival when comparing hyperbaric oxygen therapy (HBO) treatment with no HBO treatment after adjustment for age and co-morbidities such as drug abuse, psychiatric disease, stroke, alcohol abuse, arterial embolism, chronic obstructive pulmonary disease, cerebrovascular disease and atrial fibrillation. Several co-morbidities predicted poorer outcomes for patients who survived the initial 30 days. CONCLUSIONS: Poisoning from smoke and/or CO is a frequent incident in Denmark accounting for numerous contacts with hospitals and deaths. Both intoxication and mortality are highly associated with co-morbidities interfering with cognitive and physical function. Treatment with HBO was not seen to have an effect on survival. PMID: 30653615 [PubMed - in process]

Superoxide Radical Photogenerator with Amplification Effect: Surmounting the Achilles' heels of Photodynamic Oncotherapy.

Related Articles Superoxide Radical Photogenerator with Amplification Effect: Surmounting the Achilles' heels of Photodynamic Oncotherapy. J Am Chem Soc. 2019 Jan 17;: Authors: Li M, Xiong T, Du J, Tian R, Xiao M, Guo L, Long S, Fan J, Sun W, Shao K, Song X, Foley JW, Peng X Abstract Strong oxygen dependence, poor tumor targeting, and limited treatment depth have been considered as the "Achilles' heels" facing the clinical usage of photodynamic therapy (PDT). Different from common approaches, here, we propose an innovative tactic by using photon-initiated dyad cationic superoxide radical (O2-•) generator (ENBOS) featuring "0 + 1 > 1" amplification effect to simultaneously overcome these drawbacks. In particular, by taking advantage of the Förster resonance energy transfer theory, the energy donor successfully endows ENBOS with significantly enhanced NIR absorbance and photon utility, which in turn lead to ENBOS more easily activated and generating more O2-• in deep tissues, thus dramatically intensifies the type I PDT against hypoxic deep tumors. Moreover, benefiting from the dyad cationic feature, ENBOS achieves superior "structure-inherent targeting" abilities with the signal-to-background ratio as high as 25.2 at 48 h post intravenous injection, offering opportunities for accurate imaging-guided tumor treatment. Meanwhile, the intratumoral accumulation and retention performance are also markedly improved (> 120 h). Based on these unique merits, ENBOS selectively inhibits the deep-seated hypoxic tumor proliferation at a low light-dose irradiation. Therefore, this delicate design may open up new horizons and cause a paradigm change for PDT in future cancer therapy. PMID: 30652866 [PubMed - as supplied by publisher]

Gamma-Secretase Inhibitor, DAPT, Prevents the Development of Retinopathy of Prematurity in a Rat Model by Regulating the Delta-Like Ligand 4/Notch Homolog-1 (DLL4/Notch-1) Pathway.

Related Articles Gamma-Secretase Inhibitor, DAPT, Prevents the Development of Retinopathy of Prematurity in a Rat Model by Regulating the Delta-Like Ligand 4/Notch Homolog-1 (DLL4/Notch-1) Pathway. Med Sci Monit. 2019 Jan 17;25:492-499 Authors: Sun W, Li J, Li Y, Zheng J, Zhang X, Huang X, Li S Abstract BACKGROUND Retinopathy of prematurity (ROP), or retrolental fibroplasia, affects premature infants who have undergone intensive care with oxygen therapy. This study aimed to investigate the inhibitory effect of the gamma-secretase inhibitor, DAPT, on neovascularization and its mechanism in a rat model of ROP. MATERIAL AND METHODS Sixty neonatal Sprague-Dawley (SD) rats included the control group (n=20), the model group (n=20), and the DAPT-treated group (n=20). The rat model of ROP was established using repeat cycles of oxygen inhalation. Enzyme-linked immunosorbent assay (ELISA) measured serum levels of vascular endothelial growth factor (VEGF), VEGF receptor-1 (VEGFR-1), and VEGFR-2. Histology of the retinal tissue included immunohistochemistry for the expression of Notch homolog-1 (Notch-1) and delta-like ligand 4 (DLL4). Retinal mRNA levels of DLL4, Notch-1, VEGF, VEGFR-1, and VEGFR-2 were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS The rat model of ROP showed increased serum levels of VEGF, VEGFR-1, and VEGFR-2 compared with the control group, which were decreased in the DAPT group. Histology of the retinal tissue in the model group showed degeneration of the retinal ganglion cells, and immunohistochemistry showed increased expression of Notch-1 and DLL4 compared with the control group and DAPT group. Retinal tissue in the model group had increased mRNA levels of DLL4, Notch-1, VEGF, VEGFR-1, and VEGFR-2 compared with the control group, and the DAPT group. CONCLUSIONS In a rat model, treatment with DAPT reduced the retinal changes associated with ROP with a mechanism that involved VEGF and its receptors through the DLL4/Notch-1 pathway. PMID: 30652694 [PubMed - in process]

A Comprehensive Review of Oxidative Stress as the Underlying Mechanism in Atherosclerosis and the Inefficiency of Antioxidants to Revert this Process.

Related Articles A Comprehensive Review of Oxidative Stress as the Underlying Mechanism in Atherosclerosis and the Inefficiency of Antioxidants to Revert this Process. Curr Pharm Des. 2019 Jan 15;: Authors: Cabezas KG, Gómez-Fernandez CR, Vazquez-Padron R Abstract BACKGROUND: Cardiovascular diseases account for the highest mortality rate in the United States. The major underlying mechanism driving the onset and maintenance of cardiovascular diseases is atherosclerosis. Atherosclerosis is a chronic disease affecting large and medium size arteries; it proceeds through four main stages along the different decades of life, beginning at birth. Atherosclerosis is a consequence of Oxidative stress, where homeostasis between endogenous antioxidants and reactive oxygen species is disrupted. Failure of intrinsic antioxidants and prophylactic antioxidant supplements to prevent atherosclerosis formation is an ongoing area of research on the race to avert, manage and cure atherosclerosis. METHODS: The purpose of this work is to elucidate the actions of reactive oxygen species and oxidative stress on the formation of atherosclerosis as well as the different stages of atherosclerosis and the different mechanisms to prevent it. Through extensive review of scientific literature, this paper correlates cell damage caused by oxidative stress to atheromatous plaque formation, as well as an in-depth analysis of high-density lipoproteins and enzymatic and non-enzymatic antioxidant role on atherosclerosis prevention. Antioxidant mechanism are overwhelmed by atherosclerotic processes and fail to be the ideal treatment of atherosclerosis. There is no scientific data that correlates prophylactic and non-prophylactic antioxidant treatment to a decrease in mortality or comorbidities pertaining to atherosclerosis. This is thought to be due to lack of consensus of optimal therapeutic doses, lack reliable markers indicating which patient is to benefit from therapy and the chemical complexity of antioxidants in vivo. Current treatments for atherosclerosis include HMG-CoA reductase inhibitors which target directly low-density lipoproteins to tackle atherosclerotic plaque formation. CONCLUSION: HMG-CoA reductase inhibitors are not enough for the treatment of atherosclerosis given the complexity of the disease which has immune, musculoskeletal, genetic and hematologic aspects besides the involvement of lipids and lipoproteins. Therefore, other pharmacologic targets such as the PCSK9 enzyme and NFK- β should be researched in depth as possible treatments for atherosclerosis. PMID: 30652635 [PubMed - as supplied by publisher]

Impact of hyperoxia on cardiac pathophysiology.

Related Articles Impact of hyperoxia on cardiac pathophysiology. J Cell Physiol. 2019 Jan 16;: Authors: Rodgers JL, Iyer D, Rodgers LE, Vanthenapalli S, Panguluri SK Abstract Mechanical ventilation with high oxygen therapy (hyperoxia) is widely implemented in critical care and ICU settings. Although supplemental oxygen is beneficial to treat hypoxia, its use is also associated with poor outcomes and high mortality in patients. Lung injury due to hyperoxia exposure has been well-documented in patients, including in adults and neonates. Thus, lung injury due to hyperoxia has been extensively researched in both preclinical and clinical studies. However, hyperoxia has also been shown to be associated with hemodynamic changes in patients in ICU, including reductions in heart rate, stroke volume, and cardiac output. In addition, certain experimental studies report that hyperoxia exposure in neonates results in cardiac dysfunction in later adult life. Despite this, until recently, the impact of hyperoxia within the heart has not been well studied, or reported, specifically in adult experimental models. To close this significant gap, our lab has sought to clarify hyperoxia-induced cardiac pathophysiology in adult murine models. This review discusses the current findings regarding the cardiovascular impact of hyperoxia exposure. PMID: 30652312 [PubMed - as supplied by publisher]

Low-Concentration Oxygen/Ozone Treatment Attenuated Radiculitis and Mechanical Allodynia via PDE2A-cAMP/cGMP-NF-κB/p65 Signaling in Chronic Radiculitis Rats.

Related Articles Low-Concentration Oxygen/Ozone Treatment Attenuated Radiculitis and Mechanical Allodynia via PDE2A-cAMP/cGMP-NF-κB/p65 Signaling in Chronic Radiculitis Rats. Pain Res Manag. 2018;2018:5192814 Authors: Wang J, Wu M, Lin X, Li Y, Fu Z Abstract Background: Oxygen/ozone therapy is a minimally invasive technique for the treatment of radiculitis from lumbar disc herniation. This study aimed at investigating whether intrathecal administration of low-concentration oxygen/ozone could attenuate chronic radiculitis and mechanical allodynia after noncompressive lumbar disc herniation and at elucidating the underlying mechanisms. Methods: First, we transplanted autologous nucleus pulposus into dorsal root ganglions to establish chronic radiculitis in rats. Then, filtered oxygen or oxygen/ozone (10, 20, or 30 μg/mL) was intrathecally injected on day 1 after surgery. The ipsilateral paw withdrawal thresholds (PWTs) to mechanical stimuli were tested daily with von Frey filaments. The expression of the tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, IL-6, cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), phosphodiesterase 2A (PDE2A), and nuclear factor- (NF-) κB/p65 in spinal dorsal horns was measured by enzyme-linked immunosorbent assay, polymerase chain reaction, and western blot on day 7 after surgery. Results: Chronic radiculitis was established in rats. Intrathecal administration of 10 μg/mL, 20 μg/mL, or 30 μg/mL oxygen/ozone significantly attenuated the decreased mechanical PWTs, downregulated the overexpression of spinal TNF-α, IL-1β, and IL-6, and increased the expression of cGMP and cAMP in chronic radiculitis rats. In addition, the effects of treatment with 20 μg/mL oxygen/ozone were greater than the effects of the 10 μg/mL or 30 μg/mL doses. Moreover, intrathecal administration of 20 μg/mL oxygen/ozone reversed the increased levels of spinal PDE2A and NF-κB/p65 mRNA and protein expressions in rats with chronic radiculitis. Conclusion: Intrathecal administration of low-concentration oxygen/ozone alleviated mechanical allodynia and attenuated radiculitis, likely by a PDE2A-cGMP/cAMP-NF-κB/p65 signaling pathway in chronic radiculitis rats. PMID: 30651902 [PubMed - in process]

The Siconolfi step test: a valid and reliable assessment of cardiopulmonary fitness in older men with prostate cancer.

Related Articles The Siconolfi step test: a valid and reliable assessment of cardiopulmonary fitness in older men with prostate cancer. Eur Rev Aging Phys Act. 2019;16:1 Authors: Lemanska A, Poole K, Aning JJ, Griffin BA, Manders R, Saxton JM, Wainwright J, Faithfull S Abstract Background: Assessing fitness and promoting regular physical activity can improve health outcomes and early recovery in prostate cancer. This is however, underutilised in clinical practice. The cardiopulmonary exercise test (CPET) is increasingly being used pre-treatment to measure aerobic capacity and peak oxygen consumption (VO2peak - a gold standard in cardiopulmonary fitness assessment). However, CPET requires expensive equipment and may not always be appropriate. The Siconolfi step test (SST) is simpler and cheaper, and could provide an alternative.The aim of this study was to evaluate the validity and reliability of SST for predicting cardiopulmonary fitness in men with prostate cancer. Men were recruited to this two-centre study (Surrey and Newcastle, United Kingdom) after treatment for locally advanced prostate cancer. They had one or more of three risk factors: elevated blood pressure, overweight (BMI > 25), or androgen deprivation therapy (ADT). Cardiopulmonary fitness was measured using SST and cycle ergometry CPET, at two visits three months apart. The validity of SST was assessed by comparing it to CPET. The VO2peak predicted from SST was compared to the VO2peak directly measured with CPET. The reliability of SST was assessed by comparing repeated measures. Bland-Altman analysis was used to derive limits of agreement in validity and reliability analysis. Results: Sixty-six men provided data for both SST and CPET. These data were used for validity analysis. 56 men provided SST data on both visits. These data were used for reliability analysis. SST provided valid prediction of the cardiopulmonary fitness in men > 60 years old. The average difference between CPET and SST was 0.64 ml/kg/min with non-significant positive bias towards CPET (P = 0.217). Bland-Altman 95% limits of agreement of SST with CPET were ± 7.62 ml/kg/min. SST was reliable across the whole age range. Predicted VO2peak was on average 0.53 ml/kg/min higher at Visit 2 than at Visit 1 (P = 0.181). Bland-Altman 95% limits of agreement between repeated SST measures were ± 5.84 ml/kg/min. Conclusions: SST provides a valid and reliable alternative to CPET for the assessment of cardiopulmonary fitness in older men with prostate cancer. Caution is advised when assessing men 60 years old or younger because the VO2peak predicted with SST was significantly lower than that measured with CPET. PMID: 30651889 [PubMed]

Therapeutic effect of combined hyperbaric oxygen and radiation therapy for single brain metastasis and its influence on osteopontin and MMP-9.

Related Articles Therapeutic effect of combined hyperbaric oxygen and radiation therapy for single brain metastasis and its influence on osteopontin and MMP-9. Exp Ther Med. 2019 Jan;17(1):465-471 Authors: Tao J, Gao Z, Huang R, Li H Abstract The present study aimed to investigate the therapeutic effect of combined hyperbaric oxygen and radiation therapy for the treatment of single brain metastasis (SBM), as well as its influence on osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9). A total of 86 patients with SBM were admitted to Hongqi Hospital from January 2013 to January 2016 and those included within the study were randomly divided into two groups. The control group was only treated with whole brain radiotherapy, while the observation group was treated with hyperbaric oxygenation combined with whole brain radiotherapy. OPN and MMP-9 expression was measured in each group by ELISA and the results prior to and following treatment were compared. The total effective rate (patients with complete remission, partial remission or stabilized lesions) in the observation group (95.3%) was significantly increased compared with the control group (67.4%). However, the OPN and MMP-9 protein levels observed in the observation group were significantly reduced compared with the control group (P<0.05). In addition, the quality of life and the incidence of adverse reactions in the observation group were significantly improved compared with the control group (P<0.05). For patients with SBM, hyperbaric oxygenation combined with radiotherapy may improve the efficiency of treatment and should be considered for further investigation and use within a clinical setting. PMID: 30651823 [PubMed]

Evaluation of glutathione peroxidase in the blood and tumor tissue of oral squamous cell carcinoma patients.

Related Articles Evaluation of glutathione peroxidase in the blood and tumor tissue of oral squamous cell carcinoma patients. J Oral Maxillofac Pathol. 2018 Sep-Dec;22(3):447 Authors: Deshpande KC, Kulkarni MM, Rajput DV Abstract Aims and Objectives: The lowered antioxidant capacity and the oxidant-antioxidant imbalance have been considered to play a role in multistage carcinogenesis. The deleterious effects produced by reactive oxygen species depend on the imbalance between oxidant and antioxidant status in the body, so this study is aimed to evaluate the levels of antioxidant enzyme, glutathione peroxidase (GPx), in the blood and tumor tissues of oral squamous cell carcinoma (OSCC) patients in comparison with healthy controls. Materials and Methods: The study comprised of 38 participants divided into two groups. Group 1 comprised of 20 patients with OSCC and Group 2 comprised of age- and sex-matched 18 healthy individuals free of any habits and systemic illness. The levels of GPx were estimated in the blood and tissue samples in both groups by Paglia and Valentine method using a Commercial Biochemical assay kit (RANDOX), by ultraviolet-visible spectrophotometer. Results: The GPx levels were elevated in the whole blood and the tissue samples of OSCC cases as compared to the control group. It was also found that the GPx levels were increased in the tumor tissue with respect to the histopathological grading of the OSCC cases. Conclusion: Detection of antioxidant status may be useful to choose correct radiotherapy or chemotherapy, to monitor the effectiveness of the therapeutic strategy and to determine tumor resistance to therapy. Hence, the evaluation of GPx enzyme level can be used as a prognostic marker in patients with OSCC. PMID: 30651704 [PubMed]

Cascade enzymes within self-assembled hybrid nanogel mimicked neutrophil lysosomes for singlet oxygen elevated cancer therapy.

Related Articles Cascade enzymes within self-assembled hybrid nanogel mimicked neutrophil lysosomes for singlet oxygen elevated cancer therapy. Nat Commun. 2019 Jan 16;10(1):240 Authors: Wu Q, He Z, Wang X, Zhang Q, Wei Q, Ma S, Ma C, Li J, Wang Q Abstract As the first line of innate immune cells to migrate towards tumour tissue, neutrophils, can immediately kill abnormal cells and activate long-term specific adaptive immune responses. Therefore, the enzymes mediated elevation of reactive oxygen species (ROS) bioinspired by neutrophils can be a promising strategy in cancer immunotherapy. Here, we design a core-shell supramolecular hybrid nanogel via the surface phosphatase triggered self-assembly of oligopeptides around iron oxide nanoparticles to simulate productive neutrophil lysosomes. The cascade reaction of superoxide dismutase (SOD) and chloroperoxidase (CPO) within the bioinspired nanogel can convert ROS in tumour tissue to hypochlorous acid (HOCl) and the subsequent singlet oxygen (1O2) species. Studies on both cells and animals demonstrate successful 1O2-mediated cell/tumour proliferation inhibition, making this enzyme therapy capable for treating tumours without external energy activation. PMID: 30651559 [PubMed - in process]

Is an IOTA of evidence enough?

Related Articles Is an IOTA of evidence enough? CJEM. 2019 Jan 17;:1-3 Authors: Davis SNP, Di Nicola N, Gosselin S Abstract Clinical questionDo patients with acute illness admitted to the hospital and treated with liberal oxygen therapy compared with those treated with conservative oxygen therapy have differences in mortality and morbidity?Article chosenChu DK, Kim LH, Young PJ, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet 2018;391(10131):1693-705. OBJECTIVES: To analyse the existing literature to assess the potential benefits or harms of supplemental oxygen use in acutely ill patients. PMID: 30651153 [PubMed - as supplied by publisher]

On the Mechanism of Hyperthermia-Induced BRCA2 Protein Degradation.

Related Articles On the Mechanism of Hyperthermia-Induced BRCA2 Protein Degradation. Cancers (Basel). 2019 Jan 15;11(1): Authors: van den Tempel N, Zelensky AN, Odijk H, Laffeber C, Schmidt CK, Brandsma I, Demmers J, Krawczyk PM, Kanaar R Abstract The DNA damage response (DDR) is a designation for a number of pathways that protects our DNA from various damaging agents. In normal cells, the DDR is extremely important for maintaining genome integrity, but in cancer cells these mechanisms counteract therapy-induced DNA damage. Inhibition of the DDR could therefore be used to increase the efficacy of anti-cancer treatments. Hyperthermia is an example of such a treatment-it inhibits a sub-pathway of the DDR, called homologous recombination (HR). It does so by inducing proteasomal degradation of BRCA2 -one of the key HR factors. Understanding the precise mechanism that mediates this degradation is important for our understanding of how hyperthermia affects therapy and how homologous recombination and BRCA2 itself function. In addition, mechanistic insight into the process of hyperthermia-induced BRCA2 degradation can yield new therapeutic strategies to enhance the effects of local hyperthermia or to inhibit HR. Here, we investigate the mechanisms driving hyperthermia-induced BRCA2 degradation. We find that BRCA2 degradation is evolutionarily conserved, that BRCA2 stability is dependent on HSP90, that ubiquitin might not be involved in directly targeting BRCA2 for protein degradation via the proteasome, and that BRCA2 degradation might be modulated by oxidative stress and radical scavengers. PMID: 30650591 [PubMed]

Can Early Introduction of Palliative Care Limit Intensive Care, Emergency and Hospital Admissions in Patients with Severe Chronic Obstructive Pulmonary Disease? A Pilot Randomized Study.

Related Articles Can Early Introduction of Palliative Care Limit Intensive Care, Emergency and Hospital Admissions in Patients with Severe Chronic Obstructive Pulmonary Disease? A Pilot Randomized Study. Respiration. 2019 Jan 16;:1-10 Authors: Janssens JP, Weber C, Herrmann FR, Cantero C, Pessina A, Matis C, Merlet Viollet R, Boiche-Brouillard L, Stirnemann J, Pautex S Abstract BACKGROUND: Despite their poor prognosis, patients with severe chronic obstructive pulmonary disease (COPD) have little access to palliative care and tend to have a high rate of hospital and intensive care unit (ICU) admissions during their last year of life. OBJECTIVES: To determine the feasibility of a home palliative care intervention during 1 year versus usual care, and the possible impact of this intervention on emergency, hospital and ICU admissions, survival, mood, and health-related quality of life (HRQL). METHODS: Prospective controlled study of patients with severe COPD (GOLD stage III or IV) and long-term oxygen therapy and/or home noninvasive ventilation and/or one or more hospital admissions in the previous year for acute exacerbation, randomized to usual care versus usual care with add-on monthly intervention by palliative care specialists at home for 12 months. RESULTS: Of 315 patients screened, 49 (15.5%) were randomized (26 to early palliative care; 23 to the control group); aged (mean ± SD) 71 ± 8 years; FEV1 was 37 ± 14% predicted; 88% with a COPD assessment test score > 10; 69% on long-term oxygen therapy or home noninvasive ventilation. The patients accepted the intervention and completed the assessment scales. After 1 year, there was no difference between groups in symptoms, HRQL and mood, and there was a nonsignificant trend for higher admission rates to hospital and emergency wards in the intervention group. CONCLUSION: Although this pilot study was underpowered to formally exclude a benefit from palliative care in severe COPD, it raises several questions as to patient selection, reluctance to palliative care in this group, and modalities of future trials. PMID: 30650418 [PubMed - as supplied by publisher]

Alveolar Macrophage Apoptosis-Associated Bacterial Killing Helps Prevent Murine Pneumonia.

Related Articles Alveolar Macrophage Apoptosis-Associated Bacterial Killing Helps Prevent Murine Pneumonia. Am J Respir Crit Care Med. 2019 Jan 16;: Authors: Preston JA, Bewley MA, Marriott HM, Houghton AM, Mohasin M, Jubrail J, Morris L, Stephenson YL, Cross S, Greaves DR, Craig RW, van Rooijen N, Bingle CD, Read RC, Mitchell TJ, Whyte MKB, Shapiro SD, Dockrell DH Abstract RATIONALE: Antimicrobial resistance challenges therapy of pneumonia. Enhancing macrophage microbicidal responses would combat this problem but is limited by our understanding of how alveolar macrophages (AM) kill bacteria. OBJECTIVES: To define the role and mechanism of AM apoptosis-associated bacterial killing in the lung. METHODS: We generated a unique CD68.hMcl-1 transgenic mouse with macrophage-specific over-expression of the human anti-apoptotic Mcl-1 protein, a factor upregulated in AM from patients at increased risk of community-acquired pneumonia, to address the requirement for apoptosis-associated killing. MEASUREMENTS AND MAIN RESULTS: Wild-type and transgenic macrophages demonstrated comparable ingestion and initial phagolysosomal killing of bacteria. Continued ingestion (for > 12 h) overwhelmed initial killing and a second late-phase microbicidal response killed viable bacteria in wild-type macrophages, but this response was blunted in CD68.hMcl-1 transgenic macrophages. The late-phase of bacterial killing required both caspase-induced generation of mitochondrial reactive oxygen species (mROS) and nitric oxide (NO), whose peak generation coincided with the late-phase of killing. The CD68.hMcl-1 transgene prevented mROS but not NO generation. Apoptosis-associated killing enhanced pulmonary clearance of Streptococcus pneumoniae and Haemophilus influenzae in wild-type but not CD68.hMcl-1 transgenic mice. Bacterial clearance was enhanced in vivo in CD68.hMcl-1 transgenic mice by reconstitution of apoptosis with BH3 mimetics or clodronate-encapsulated liposomes. Apoptosis-associated killing was not activated during Staphylococcus aureus lung infection. CONCLUSIONS: Mcl-1 upregulation prevents macrophage apoptosis-associated killing and establishes that apoptosis-associated killing is required to allow AM to clear ingested bacteria. Engagement of macrophage apoptosis should be investigated as a novel host-based antimicrobial strategy. PMID: 30649895 [PubMed - as supplied by publisher]

Nanohydroxyapatite exerts cytotoxic effects and prevents cellular proliferation and migration in glioma cells.

Related Articles Nanohydroxyapatite exerts cytotoxic effects and prevents cellular proliferation and migration in glioma cells. Toxicol Sci. 2019 Jan 15;: Authors: Gorojod RM, Porte Alcon S, Dittler ML, Gonzalez MC, Kotler ML Abstract Hydroxyapatite (Ca10(PO4)6(OH)2; HAP) is an essential component of the human bone inorganic phase. At the nanoscale level, nanoHAP (nHAP) presents marked emergent properties differing substantially from those of the bulk counterpart. Interestingly, these properties depend on nanoparticle characteristics. In this study, we investigated the cytotoxicity of rod-shaped crystalline nHAP (10- 20 nm x 50- 100 nm) in both normal (ARPE-19, BV-2) and tumoral (HepG2, HEp-2, A549 and C6) cells. We found that nHAP was cytotoxic in tumor HEp-2, A549 and C6 cells. Moreover, it induced an expansion of the lysosomal compartment at sub-lethal concentrations in different cell lines, while lysosomal membrane damage was not detected. In C6 glioma cells, the most sensitive cell line to nHAP, these nanoparticles increased reactive oxygen species (ROS) production and induced DNA damage measured by γ-H2AX phosphorylation. Interestingly, our data also shows for the first time that nHAP affects both cell unlimited proliferative capacity and cell migration, two of the major pathways involved in cancer progression. The present results showed the cytotoxic and antiproliferative effects of nHAP and suggest its potential as an alternative agent for glioma therapy. PMID: 30649537 [PubMed - as supplied by publisher]

Cardiac output monitoring: Technology and choice.

Related Articles Cardiac output monitoring: Technology and choice. Ann Card Anaesth. 2019 Jan-Mar;22(1):6-17 Authors: Kobe J, Mishra N, Arya VK, Al-Moustadi W, Nates W, Kumar B Abstract The accurate quantification of cardiac output (CO) is given vital importance in modern medical practice, especially in high-risk surgical and critically ill patients. CO monitoring together with perioperative protocols to guide intravenous fluid therapy and inotropic support with the aim of improving CO and oxygen delivery has shown to improve perioperative outcomes in high-risk surgical patients. Understanding of the underlying principles of CO measuring devices helps in knowing the limitations of their use and allows more effective and safer utilization. At present, no single CO monitoring device can meet all the clinical requirements considering the limitations of diverse CO monitoring techniques. The evidence for the minimally invasive CO monitoring is conflicting; however, different CO monitoring devices may be used during the clinical course of patients as an integrated approach based on their invasiveness and the need for additional hemodynamic data. These devices add numerical trend information for anesthesiologists and intensivists to use in determining the most appropriate management of their patients and at present, do not completely prohibit but do increasingly limit the use of the pulmonary artery catheter. PMID: 30648673 [PubMed - in process]
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