Oxygen therapy for sepsis and prevention of complications.

Patients with sepsis have a wide range of respiratory disorders that can be treated with oxygen therapy. Experimental data in animal sepsis models show that oxygen therapy significantly increases survival, while clinical data on the use of different oxygen therapy protocols are ambiguous. Oxygen therapy, especially hyperbaric oxygenation, in patients with sepsis can aggravate existing oxidative stress and contribute to the development of disseminated intravascular coagulation. The purpose of this article is to compare experimental and clinical data on oxygen therapy in animals and humans, to discuss factors that can influence the results of oxygen therapy for sepsis treatment in humans, and to provide some recommendations for reducing oxidative stress and preventing disseminated intravascular coagulation during oxygen therapy.

Oxycytosis and the role of triboelectricity and oxidation in bacteria clearing from the bloodstream.

Until recently, little was known about the mechanism for killing and clearing bacteria from the bloodstream. Leukocyte phagocytosis could not be a mechanism for catching, killing and removing bacteria from the bloodstream because of many reasons. Recently accumulated data have led to the conclusion that in bacteremia, bacteria are quickly removed from the blood and erythrocytes are the main cells that capture, kill and remove bacteria. Data were also obtained that erythrocytes catch bacteria by triboelectric charge attraction and kill them by oxygen released from oxyhemoglobin. This phenomenon has been named oxycytosis by analogy with the term phagocytosis. Oxycytosis has been discussed in a number of published articles, but the specific mechanism of triboelectric charging and the mechanism of killing bacteria by oxidation, have not yet been detailed. The purpose of this review is to provide a more detailed explanation of the process of triboelectric charging and capture of bacteria by erythrocytes and destruction of bacteria by oxidation. For the first time, the review presents various variants of oxycytosis (two-stage, three-stage, multi-stage), depending on the resistance of the pathogen to oxidation. The review also discusses the biological significance of oxycytosis and its impact on the understanding of bacteremia and sepsis.

Rototrichous: a new type of bacterial flagellation.

A rod-shaped microorganism with unknown type of flagellation has been accidentally discovered during phase-contrast microscopy of a sample of contaminated human donor blood. The flagellum consists of three fragments that form a complex locomotor device attached to bacterial body. The device provides bacterial motility by rotating around longitudinal axis of bacterial body and so this type of flagellation has been named "rototrichous." This newly discovered bacterial flagellation should be included in the classification of bacterial flagellations.

Sepsis: mechanisms of bacterial injury to the patient.

In bacteremia the majority of bacterial species are killed by oxidation on the surface of erythrocytes and digested by local phagocytes in the liver and the spleen. Sepsis-causing bacteria overcome this mechanism of human innate immunity by versatile respiration, production of antioxidant enzymes, hemolysins, exo- and endotoxins, exopolymers and other factors that suppress host defense and provide bacterial survival. Entering the bloodstream in different forms (planktonic, encapsulated, L-form, biofilm fragments), they cause different types of sepsis (fulminant, acute, subacute, chronic, etc.). Sepsis treatment includes antibacterial therapy, support of host vital functions and restore of homeostasis. A bacterium killing is only one of numerous aspects of antibacterial therapy. The latter should inhibit the production of bacterial antioxidant enzymes and hemolysins, neutralize bacterial toxins, modulate bacterial respiration, increase host tolerance to bacterial products, facilitate host bactericidal mechanism and disperse bacterial capsule and biofilm.

Blood coagulation: a powerful bactericidal mechanism of human innate immunity.

Infection proliferates and disseminates rapidly and so innate immunity should react effectively and fast. Innate immunity mechanisms depend upon fluid dynamics and are different in compartments with slow (the tissues) and rapid (the bloodstream) liquid flow. In the tissues, coagulation initiated by clotting factors, platelets and erythrocytes, is prompt and effective mechanism of the first line of antibacterial defense. Resident macrophages, transmigrated neutrophils, monocytes, NETs and platelets are the second line of the defense. In the bloodstream the first line of innate immunity defense are erythrocytes that kill pathogens by oxygen, released from oxyhemoglobin (oxycytosis); the second line of the defense is coagulation that in case of overactivation may cause disseminated intravascular coagulation (DIC). Blood coagulation is the fastest mechanism of infection confinement and inactivation. It is the first and the last line of innate immunity defense and occurs both in the tissues and the bloodstream.

Six-Coordinate Nitrato Complexes of Iron Porphyrins with Trans S-Donor Ligands.

The reaction of dimethyl sulfide (DMS) and tetrahydrothiophene (THT) with thin, amorphous layers of the nitrato complexes Fe(Por)(η2-O2NO) (Por = meso-tetraphenylporphyrinato dianion or meso-tetra- p-tolylporphyrinato dianion) at low temperature leads to formation of the corresponding six-coordinate complexes Fe(Por)(L)(η1-ONO2) (L = DMS, THT) as characterized by Fourier transform infrared and optical spectroscopy measurements. Adduct formation was accompanied by bidentate-to-monodentate linkage isomerization of the nitrato ligand, with the FeIII center remaining in a high-spin electronic state. These adducts are thermally unstable; warming to room temperature restores the initial Fe(Por)(η2-O2NO) species.

Phagocytosis and oxycytosis: two arms of human innate immunity.

Human innate immunity operates in two compartments: extravascular (the tissues) and intravascular (the bloodstream). Physical conditions (fluid dynamics) in the compartments are different and, as a result, bactericidal mechanisms and involved cells are different as well. In relatively static media (the tissues, lymph nodes), bacteria are killed by phagocytes; in dynamic media (the bloodstream), bacteria are killed by erythrocytes. In the tissues and lymph nodes, resident macrophages and transmigrated from blood leukocytes (neutrophils and monocytes) recognize, engulf, kill, and digest bacteria; the clearance of the bloodstream from bacteria is performed by oxycytosis: erythrocytes catch bacteria by electric charge attraction and kill them by the oxygen released from oxyhemoglobin. Killed by erythrocytes, bacteria are decomposed and digested in the liver and the spleen. Phagocytosis by leukocytes in the tissues and oxycytosis by erythrocytes in the bloodstream are the main bactericidal mechanisms of human innate immunity.

Venous pressure during intravenous regional anesthesia: Implications for setting tourniquet pressure.

BACKGROUND AND AIMS: Intravenous regional anesthesia (IVRA) is utilized for upper extremity surgery, but higher tourniquet pressure and longer inflation time increase the risk of soft tissue and nerve injury. We investigated the duration and magnitude of elevated venous pressure during IVRA to assess the possibility of safely lowering the tourniquet pressure during surgery. MATERIAL AND METHODS: Twenty adult patients scheduled for distal upper extremity surgery were enrolled. An additional intravenous catheter was placed in the surgical arm connected to a digital pressure transducer for monitoring venous pressure. Venous pressure was recorded prior to IVRA and every 30 s after injection of local anesthetic (LA) until the completion of surgery. RESULTS: All 20 subjects completed the study without complication. Peak venous pressure was 340 mmHg in one patient which lasted for less than 30 s. Mean venous pressures fell below systolic blood pressure after 4.5 min in all cases except one. This patient had elevated venous pressures for 24 of 25 min of tourniquet time exceeding systolic blood pressure. The only statistically significant intraoperative factor associated with elevated venous pressure was elevated peak systolic pressure (P = 0.001). CONCLUSIONS: We found that the mean peak venous pressure was below systolic blood pressure in only 14 of the 20 subjects, and the peak injection pressure exceeded 300 mmHg in one patient. Another patient's venous pressure remained above systolic blood pressure for 24 of 25 min of tourniquet time. Current precautions to prevent LA toxicity may be insufficient in some patients and attempts to lower tourniquet pressures to just above systolic blood pressures soon after IVRA injection may result in toxicity, specifically if systolic pressure is elevated.

Sepsis and septic shock: Pathogenesis and treatment perspectives.

The majority of bacteremias do not develop to sepsis: bacteria are cleared from the bloodstream. Oxygen released from erythrocytes and humoral immunity kill bacteria in the bloodstream. Sepsis develops if bacteria are resistant to oxidation and proliferate in erythrocytes. Bacteria provoke oxygen release from erythrocytes to arterial blood. Abundant release of oxygen to the plasma triggers a cascade of events that cause: 1. oxygen delivery failure to cells; 2. oxidation of plasma components that impairs humoral regulation and inactivates immune complexes; 3. disseminated intravascular coagulation and multiple organs' failure. Bacterial reservoir inside erythrocytes provides the long-term survival of bacteria and is the cause of ineffectiveness of antibiotics and host immune reactions. Treatment perspectives that include different aspects of sepsis development are discussed.

Mechanisms and pathways for the clearance of bacteria from blood circulation in health and disease.

Available data do not support the concept that leukocytes engulf and kill bacteria in the bloodstream. Leukocytes cannot recognize or engulf bacteria in flowing blood; therefore, phagocytosis is impossible in the bloodstream and occurs instead outside of the bloodstream in the body tissues. Erythrocytes capture bacteria in the circulation using an electric charge and kill them using oxidation. The dead bacteria are then disintegrated and digested by the reticuloendothelial system (RES), particularly in the liver and the spleen.

Monitoring minute ventilation versus respiratory rate to measure the adequacy of ventilation in patients undergoing upper endoscopic procedures.

Endoscopic procedures performed under conscious sedation require careful monitoring of respiratory status to prevent adverse outcomes. This study utilizes a non-invasive respiratory volume monitor (RVM) that provides continuous real-time measurements of minute ventilation (MV), tidal volume and respiratory rate (RR) to assess the adequacy of ventilation during endoscopy. Digital respiratory traces were collected from 51 patients undergoing upper endoscopy with propofol sedation using an impedance-based RVM. Baseline MV for each patient was derived from a 30 s period of quiet breathing prior to sedation (MVBASELINE). Capnography data were also collected. Because RR from capnography was frequently unavailable, the RVM RR's were used for analysis. RR rate values were compared the MV measurements and sensitivity and specificity of RR to predict inadequate ventilation (MV <40 % MVBASELINE) were calculated. Initial analysis revealed that there is a weak correlation between an MV measurement and its corresponding RR measurement (r = 0.05). If MV is an actual indictor of respiratory performance, using RR as a proxy is grossly inadequate. Simulating a variety of RR alarm conditions [4-8 breaths/min (bpm)] showed that a substantial fraction of low MV measurements (MV <40 % MVBASELINE) went undetected (at 8 bpm, >70 % low MV measurements were missed; at 6 bpm, >82 % were missed; and at 4 bpm, >90 % were missed). A cut-off of 6 bpm had a sensitivity of only 18.2 %; while <40 % of all RR alarms would have coincided with a low MV (39.4 % PPV). Low RR measurements alone do not reflect episodes of low MV and are not sufficient for accurate assessment of respiratory status. RVM provides a new way to collect MV measurements which provide more comprehensive data than RR alone. Further work is ongoing to evaluate the use of MV data during procedural sedation.

Erythrocyte and leukocyte: two partners in bacteria killing.

Leukocytes can't perform phagocytosis in blood stream. Blood velocity prevents phagocytosis because there is no time for leukocyte to recognize and catch bacteria. Bloodstream clearance from pathogens is performed by erythrocytes. During motion in bloodstream erythrocytes become charged by triboelectric effect. This charge attracts bacteria and fixes them on the surface of erythrocyte, then bacteria are engulfed and killed by hemoglobin oxygen. In bloodstream, leukocyte thin-wrinkled elastic membrane can't be charged by triboelectric effect and so leukocyte can't catch bacteria by means of electrostatic attraction force. Leukocytes engulf and kill bacteria out of blood circulatory system: in tissues, lymph nodes, slow velocity lymph, etc. Erythrocyte and leukocyte are bactericidal partners: the first kills bacteria in bloodstream, the second kills them locally, out of blood circulation.

Erythrocyte and blood antibacterial defense.

It is an axiom that blood cellular immunity is provided by leukocytes. As to erythrocytes, it is generally accepted that their main function is respiration. Our research provides objective video and photo evidence regarding erythrocyte bactericidal function. Phase-contrast immersion vital microscopy of the blood of patients with bacteremia was performed, and the process of bacteria entrapping and killing by erythrocytes was shot by means of video camera. Video evidence demonstrates that human erythrocytes take active part in blood bactericidal action and can repeatedly engulf and kill bacteria of different species and size. Erythrocytes are extremely important integral part of human blood cellular immunity. COMPARED WITH PHAGOCYTIC LEUKOCYTES, THE ERYTHROCYTES: a) are more numerous; b) are able to entrap and kill microorganisms repeatedly without being injured; c) are more resistant to infection and better withstand the attacks of pathogens; d) have longer life span and are produced faster; e) are inauspicious media for proliferation of microbes and do not support replication of chlamidiae, mycoplasmas, rickettsiae, viruses, etc.; and f) are more effective and uncompromised bacterial killers. Blood cellular immunity theory and traditional view regarding the function of erythrocytes in human blood should be revised.

Cataract halos: a driving hazard in aging populations. Implication of the Halometer DG test for assessment of intraocular light scatter.

OBJECTIVE AND BACKGROUND: Cataract, regardless of etiology, results in light scatter and subjective glare. Senile cataract is emerging as a crucial factor in driving safely, particularly in night driving and adverse weather conditions. The authors examined this visual impairment using a new Halometer DG test in the eyes of older adult drivers with and without cataract. METHOD: Examined subjects consisted of n=65 older adults with cataract in one or both eyes and n=72 adult drivers who did not have a cataract in either eye. Subjects were examined for distance high contrast visual acuity (VA) and red/green disability glare (DG) with a new halo generating instrument. Subjects also completed a subjective Driving Habits Questionnaire (DHQ), designed to obtain information about driving during the past year. RESULTS: DG increased with age of the driver. VA and Halometer DG testing of better and worse eyes prognosticated impairments which significantly affect driving performance. Cataract subjects demonstrated increased Halometer DG scores and were two to four times more likely to report difficulty with driving at night and with challenging driving situations than were cataract-free drivers. CONCLUSION: DG is a specific cataract-induced functional age-related risk factor of driving difficulty, easily measured by a technician with a new Halometer DG device. APPLICATION: Optometrists and ophthalmologists should incorporate Halometer DG testing in their pre-examination vision testing rooms for patients over age 55, and also perform this test on others who complain about glare. Traffic safety engineers should incorporate automotive optical-microprocessor-aided tests for DG into cars, to alert drivers of mild functional impairments and progressive degrees of DG sensitization.