Robert P. Ostrowski

Effect of coenzyme Q10 on biochemical and morphological changes in experimental ischemia in the rat brain

Abstract The aim of the work was to evaluate an influence of CoQ10 on lactate acidosis, adenosine-5′-triphosphate (ATP) concentrations, oxidized to reduced glutathione ratio and on superoxide dismutase activity in endothelin model of cerebral ischemia in the rat. Light microscopic studies in the central nervous system and morphometric analysis of pyramidal cells in the hippocampus were also performed. Endothelins (ET-1 or ET-3; 20 pmoles) were injected into the right lateral cerebral ventricle (intracerebroventricularly). CoQ10 was given intraperitoneally (i.p.) just before the operation (i.p. 10 mg\kg b. wt.). More severe changes of investigated biochemical parameters were observed in the animals treated with ET-1 in comparison with ET-3. Recovery was noted earlier in the group subjected to ET-3 and CoQ10 administration, than in the animals subjected to ET-1 and CoQ10 treatment. Histopathological observations showed sparse foci of a neuronal loss in the cerebral cortex and in the hippocampus only in the ET-1 model of ischemia. Additionally more numerous dark neurons were present in above brain structures following ET-1 administration comparing with ET-3 one. Morphometrical studies demonstrated that CoQ10 diminished neuronal injury in the hippocampal CA1, CA2 and CA3 zones. Above data indicate on neuroprotective effect of CoQ10 as a potent antioxidant and oxygen derived free radicals scavenger in the cerebral ischemia.

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.

Effect of endothelin receptor antagonist bosentan on plasma leptin concentration in acute myocardial infarction in rats

The aim of the study was to evaluate the effect of endothelin receptor antagonism on plasma leptin level after myocardial infarction (MI). In Wistar rats under chloral hydrate anesthesia, MI was performed by ligation of the left coronary artery. The animals were divided into the following groups: control-sham (thoracotomy only), and two MI groups with or without bosentan treatment. Bosentan was given daily by gavage at the dose of 100 mg/kg. Treatment of animals started 2 days before MI and continued up to the fifth day. Concentration of leptin was measured by radioimmunoassay by means of 125I labeled antigen in the following time intervals: before MI or sham operation, 4, 24 and 48 h after surgery. Electrocardiogram (ECG), blood pressure, heart rate, arterial pO(2), pCO(2) and pH were periodically monitored. Two days after the MI animals were perfused retrograde into descending aorta with 2% triphenyltetrazolium chloride (TTC) and hearts were fixed by immersion in formalin for microscopic examination. Hearts were sectioned transaxially and size of MI was quantitated with morphometric methods. ECG, TTC staining and microscopic results confirmed development of MI. Morphometric methods did not show significant differences in infarct size between bosentan treated and untreated groups. Concentration of leptin in plasma in untreated group significantly increased already 4 h after MI. In bosentan treated animals this increase appeared only after 24 h. In animals treated with bosentan also a significant diminution of MI mortality was observed. Our results indicate that bosentan has an important effect on leptin concentration in ischemic cardiovascular pathology.

Research of medical gases in Poland

Research of medical gases is well established in Poland and has been marked with the foundation of several professional societies. Numerous academic centers including those dealing with hyperbaric and diving medicine conduct studies of medical gases, in vast majority supported with intramural funds. In general, Polish research of medical gases is very much clinical in nature, covering new applications and safety of medical gases in medicine; on the other hand there are several academic centers pursuing preclinical studies, and elaborating basic theories of gas physiology and mathematical modeling of gas exchange. What dominates is research dealing with oxygen and ozone as well as studies of anesthetic gases and their applications. Finally, several research directions involving noble gas, hydrogen and hydrogen sulfide for cell protection, only begin to gain recognition of basic scientists and clinicians. However, further developments require more monetary spending on research and clinical testing as well as formation of new collective bodies for coordinating efforts in this matter.

Hyperbaric oxygen modalities are differentially effective in distinct brain ischemia models

The effectiveness and efficacy of hyperbaric oxygen (HBO) preconditioning and post-treatment modalities have been demonstrated in experimental models of ischemic cerebrovascular diseases, including global brain ischemia, transient focal and permanent focal cerebral ischemia, and experimental neonatal hypoxia-ischemia encephalopathy. In general, early and repetitive post-treatment of HBO appears to create enhanced protection against brain ischemia whereas delayed HBO treatment after transient focal ischemia may even aggravate brain injury. This review advocates the level of injury reduction upon HBO as an important component for translational evaluation of HBO based treatment modalities. The combined preconditioning and HBO post-treatment that would provide synergistic effects is also worth considering.

The efficacy of hyperbaric oxygen in hemorrhagic stroke: experimental and clinical implications

Hemorrhagic stroke, accounting for 10–30% of stroke cases, carries high rates of morbidity and mortality. This review presents the current knowledge on the efficacy of hyperbaric oxygen (HBO)-based modalities in the preclinical research on hemorrhagic stroke. Both preconditioning and post-treatment with HBO are considered as prospective therapeutic options. High efficacy of HBO therapy (HBOT) for brain hemorrhage has been noted. We found that moderate hyperbaric pressures appear optimal for therapeutic effect, while the therapeutic window of opportunity is short. HBO preconditioning offers more modest neuroprotective benefit as compared to HBO post-treatment for experimental intracerebral hemorrhage. We advocate for mandatory calculations of percent changes in the experimentally investigated indexes of HBO effectiveness and stress the need to design new clinical trials on HBO for hemorrhagic stroke.

Commentary on: "Effect of sevoflurane anesthesia on the comprehensive mRNA expression profile of the mouse hippocampus": Postoperative nausea and vomiting conundrum: RNA-seq to the rescue.

The molecular bases for anesthesiology syndromes have attracted substantial research attention in recent years. There is growing evidence to suggest that complex changes in gene expression may predispose to the unpleasant postoperative nausea and vomiting (PONV) manifestations that includes nausea, vomiting, and retching, 24–48 hours after surgery (Sanger and Andrews, 2006). PONV can be difficult to manage, and may result in serious complications. Translational research has accumulated a large body of data that can be usefully extrapolated to humans. A current research focus has been to establish how volatile anesthetics such as sevoflurane are associated with a dose-dependent increase in the risk of PONV. Studies have shown that septohippocampal inactivation mediates the general anesthesia effect, with the suggestion that disruption to this system might be associated with the pro emetic action of anesthetics, as an undesirable side effect (Ma et al., 2002). In their paper published in the current issue of Medical Gas Research, the authors hypothesized that the hippocampus, via dopaminergic neurons, may play a role in sevofluraneinduced PONV (Hayase, 2016). Using whole transcriptome sequencing technology, they collected mouse hippocampus gene expression profiles in response to sevoflurane, a known volatile anesthetic agent that induces PONV. Although a microarray-based approach would also capture expression data for thousands of genes, the RNA sequencing (RNA-seq) methodology, involving an intermediate cDNA library step, was used to generate more complete, discovery-oriented transcriptomes (Dong et al., 2015). After 1-hour anesthesia, it was shown that of 37,681 investigated genes, 5,459 were differentially expressed, including 345 that were markedly altered in response to sevoflurane. The most highly up-regulated gene was the Nogo receptor, which mediates axonal growth inhibition, and plays a role in regulating axonal regeneration and plasticity in the central nervous system. The dopamine receptor and tachykinin genes were also up-regulated. Of note, aprepitant is the first NK1 receptor (aka “tachykinin receptor 1”) antagonist approved for use as an antiemetic COMMENTARY