Introduction Cancer is affecting a growing number of persons. Still, the treatment and survival of cancer is improving. Radiation therapy is used in the treatment of cancer. Late radiation-induced injuries afflict 5-15% of irradiated patients. The urinary bladder and bowel may be affected after irradiation of cancer in the pelvic region. Symptoms can be severe, with impaired health related quality of life (HRQoL). Hyperbaric oxygen therapy (HBOT) involves breathing oxygen at high ambient pressure. HBOT can reverse radiation-induced injuries, alleviate patient-perceived symptoms, and improve HRQoL. We aimed to clarify the effects of HBOT on late radiation-induced injuries in the urinary bladder and bowel, and to clarify some of the underlying mechanisms through which HBOT exerts its effects. Methods A prospective cohort study assessed effects of HBOT on patient-perceived symptoms (Paper I). A rat study assessed reversal of radiation-induced stress with HBOT (Paper II). A methodological experiment assessed reversal of HBOT on cellular death induced by radiation (Paper III). A multi-center, randomized, controlled trial assessed patient-perceived symptoms, HRQoL, and objective clinical outcomes (Paper IV). Result HBOT can alleviate patient-perceived symptoms, reduce objective findings, and improve HRQoL in patients affected by late radiation-induced injuries (Paper I, IV). Oxidative stress and downstream effects, induced by the irradiation, can be reversed by HBOT (Paper II). Paper III outlines a method for studies on urothelial cells exposed to radiation and HBOT. Conclusion HBOT can reduce radiation-induced oxidative stress and inflammatory response. HBOT can reverse injuries induced by radiation therapy to the pelvic region, alleviate patient-perceived symptoms and lead to improved HRQoL.

No abstract

SummaryThe closely related B-subunits of cholera toxin (CTB) and Escherichia coli heat-labile enterotoxin (LTB) both bind strongly to GM1 ganglioside receptors but LTB can also bind to additional glycolipids and glycoproteins. A number of mutant CT B-subunits were generated by substituting CTB amino acids with those at the corresponding positions in LTB. These were used to investigate the influence of specific residues on receptor-binding specificity. A mutated CTB protein containing the first 25 residues of LTB in combination with LTB residues at positions 94 and 95, bound to the same extent as native LTB to both delipidized rabbit intestinal cell membranes, complex glycosphingolipids (polyglycosylceramides) and neolactotetraosylceramide, but not to non-GM1 intestinal glycosphingolipids. In contrast, when LTB amino acid substitutions in the 1-25 region were combined with those in the 75-83 region, a binding as strong as that of LTB to intestinal glycosphingolipids was observed. In addition, a mutant LTB with a single Gly-33→Asp substitution that completely lacked affinity for both GM1 and non-GM1 glycosphingolipids could still bind to receptors in the intestinal cell membranes and to polyglycosylceramides. We conclude that the extra, non-GM1 receptors for LTB consist of both sialylated and non-sialylated glycoconjugates, and that the binding to either class of receptors is influenced by different amino acid residues within the protein.

No abstract

Introduction SARS-CoV-2 affects part of the innate immune response and activates an inflammatory cascade stimulating the release of cytokines and chemokines, particularly within the lung. Indeed, the inflammatory response during COVID-19 is likely the cause for the development of acute respiratory distress syndrome (ARDS). Patients with mild symptoms also show significant changes on pulmonary CT-scan suggestive of severe inflammatory involvement. Hypothesis The overall hypothesis is that HBO 2 is safe and reduces the inflammatory response in COVID-19 pneumonitis by attenuation of the innate immune system, increase hypoxia tolerance and thereby prevent organ failure and reduce mortality. Evaluation of the hypothesis HBO 2 is used in clinical practice to treat inflammatory conditions but has not been scientifically evaluated for COVID-19. Experimental and empirical data suggests that HBO 2 may reduce inflammatory response in COVID-19. However, there are concerns regarding pulmonary safety in patients with pre-existing viral pneumonitis. Empirical data Anecdotes from “compassionate use” and two published case reports show promising results. Consequences of the hypothesis and discussion Small prospective clinical trials are on the way and we are conducting a randomized clinical trial.