Hyperosmotic Surroundings

Principles of cryotherapy

Dan S. Gombos , in Clinical Ophthalmic Oncology, 2007

Straight effects

Microscopically, the initial pass up in temperature in the extracellular space forms crystals, leading to a hyperosmotic environment, extracting h2o from the cells and causing them to shrink. Equally the temperature lowers, intracellular crystals form, leading to disruption of organelles and cell membranes. This affects the ability of membrane proteins to control intracellular ionic content. During the thawing phase, as the frozen water crystals dissolve, the extracellular infinite becomes hypotonic. Limited only by a defective cell membrane, extracellular water enters the cell and disrupts it. vii In improver, the common cold temperature physically disrupts the cellular cytoskeleton and denatures proteins. i, half-dozen

Read full chapter

URL:

https://world wide web.sciencedirect.com/science/article/pii/B9781416031673500115

Aquaporin Regulation

Jason P. Breves , in Vitamins and Hormones, 2020

3.2 Growth hormone

Growth hormone (GH) secreted from the anterior pituitary is regarded as a "SW-adapting hormone" because it promotes the survival of teleosts in hyperosmotic environments. This activity is well established in salmonids ( Sakamoto & McCormick, 2006; Sakamoto, McCormick, & Hirano, 1993), whereas evidence in non-salmonid fishes is far more than limited. Contrasting with the regulation of prolactin, the release of GH from the pituitary is stimulated past increases in extracellular/plasma osmolality (Nilsen et al., 2008; Seale, Fiess, Hirano, Cooke, & Grau, 2006; Seale et al., 2002). GH directly controls ion extrusion through branchial ionocytes expressing its cognate receptor, and indirectly through systemic (liver derived) and/or locally produced insulin-like growth-factor ane (IGF1) (Seidelin, Madsen, Byrialsen, & Kristiansen, 1999). Information in non-salmonids regarding the directly effects of IGF1 on hyposmoregulatory mechanisms is peculiarly scarce (Mancera & McCormick, 1998). While GH is likely pleiotropic in its support of SW acclimation, information technology is largely unknown whether it regulates intestinal and renal functions despite the robust expression of its receptor in these tissues (Björnsson, 1997; Fukada et al., 2004).

Read full chapter

URL:

https://www.sciencedirect.com/science/article/pii/S0083672919300846

Dysproteinemias, Plasma Jail cell Disorders, and Amyloidosis

Warren West. Piette , in Dermatological Signs of Internal Disease (Quaternary Edition), 2009

Pathogenesis

Monoclonal proteins may crusade disease directly by acting as cryoglobulins, past raising serum viscosity, or by acting every bit cold agglutinins. Cryoglobulins are immunoglobulins that precipitate on exposure to cold. They may exist unstable in other settings, such as in the hyperosmotic environs constitute in the kidneys, or in microvascular areas with a tedious claret flow. The virtually critical factor that determines the beliefs of the cryoglobulin in vivo is the temperature at which it begins to precipitate. If that temperature approaches those institute in the cutaneous microvasculature on common cold exposure, cold-induced disease is usually significant. If it precipitates just at a temperature well below room temperature, the symptoms will non be cold related. Cryoglobulins are divided into three categories, depending on their composition. Type I cryoglobulins consist of a unmarried monoclonal protein; type II are composed of a monoclonal immunoglobulin with anti-IgG (rheumatoid factor) activity that binds to polyclonal serum IgG; and type III cryoglobulins consist of polyclonal immunoglobulins, usually with anti-IgG activity, that bind to polyclonal serum IgG (a polyclonal rheumatoid factor). Roughly 5–10% of myeloma proteins and macroglobulins are cryoprecipitable. Types I and II cryoglobulinemia are ofttimes (but not always) associated with a lymphoproliferative disorder or plasma cell dyscrasia. Patients with type II cryoglobulinemia may have IgM, IgG, or IgA every bit their monoclonal rheumatoid factor. The possibility that rheumatoid gene may exist an IgM or IgA is of import considering IgM or IgA monoclonal proteins may non be detected past routine serum protein electrophoresis when spring to polyclonal IgG.

The hyperviscosity syndrome results from a meaning increase in whole blood viscosity. Such an increase may be related to an increase in the cellular elements in the claret, as in polycythemia vera or primary thrombocythemia. It may also consequence from a change in serum viscosity as a event of the presence of large amounts of monoclonal poly peptide in the blood. If immunoglobulin related, the hyperviscosity syndrome is usually caused past a monoclonal IgM protein. Monoclonal IgG or IgA can cause the hyperviscosity syndrome, but simply if the monoclonal antibody is present in the serum at college concentrations, or if the patient's serum is decumbent to self-aggregation.

Cold agglutinin affliction is actually a cold antibody-induced autoimmune hemolytic anemia. The antibiotic, usually IgM, binds to the scarlet cell in the cold and initiates complement activation; it then elutes at body temperature while the complement activation gain to reddish cell lysis. The common cold agglutinin also promotes temperature-dependent agglutination of red cells, leading to sludging or occlusion of the blood flow in the microvasculature exposed to cold temperatures.

Read full chapter

URL:

https://www.sciencedirect.com/scientific discipline/article/pii/B9781416061113000227

Fungal Adaptation to Extremely High Salt Concentrations

Cene Gostinčar , ... Ana Plemenitaš , in Advances in Practical Microbiology, 2011

C The importance of energy metabolism in Hortaea werneckii

The uniform-solute strategy of halotolerance requires high energy input to maintain the relevant compatible intracellular solute concentrations and ion homeostasis (Oren, 1999). Adaptation to high energy demands is clearly visible in H. werneckii. During long-term adaptive growth under extreme salinity, H. werneckii needs to maintain a high production of ATP, which powers various transmembrane transporters, such equally H+/glycerol symporters, Na+/H+-antiporters, and the P-blazon ATPases HwENA1/ii, either directly or through the electrochemical driving force of the proton slope (our unpublished information; Gorjan and Plemenitaš, 2006; Vaupotič and Plemenitaš, 2007a). The cells also need to actively maintain a correct intracellular pH and plasma-membrane potential, every bit well equally to synthesize compatible solutes to counteract the loss of turgor (Kogej et al., 2007; Petrovič et al., 2002 ). Therefore, an increment in energy production is ane of the fundamental adaptations that maintain the ion homeostasis and osmotic equilibrium in a hyperosmotic environment.

The functional category of genes associated with energy supply was highly represented among upregulated genes in cells growing at iv.five   M NaCl, and included genes coding for components of the electron-transport chain (HwCOB1, HwCYT1, HwCOX1) and ATP product (HwATP1, HwATP2, HwATP3), and those coding for conveying excessive cytosolic NADH into the mitochondrial respiratory chain (FAD-dependent GPD1, HwGUT2). Energy-production metabolism appears to be additionally enhanced by upregulation of genes coding for the enzymes of the glycolytic pathway (HwTDH1, HwPGK1), the tricarboxylic acrid bike (HwCIT1, HwKGD2, HwLSC2, HwMDH1, HwGDH1), the pentose-phosphate pathway (HwTKL1, HwGND2), and modulation of energy storage (HwUGP1, HwGAL10). A more eightfold upregulation of a specific mitochondrial inner-membrane Pi transporter gene, HwMIR1, further supports the thought of increased cellular ATP synthesis in the mitochondria (Vaupotič and Plemenitaš, 2007a). A supplemental energy source might also be the office of the product of the SOL13 factor that has high similarity to Leptosphaeria maculans rhodopsin, the first proven instance of a fungal low-cal-driven transmembrane proton pump (Waschuk et al., 2005). The increased free energy supply is likewise coupled with elevated poly peptide synthesis, which is supported past the upregulation of specific ribosomal protein isoforms and translation-regulating factors (HwFUN12, HwTIF1, HwEFT2, HwTEF1), upregulation of components of the poly peptide quality command and the unfolded protein response (HwHSP82, HwSSA4, HwERV25, HwRPN2, HwSTT3, HwIRE1, HwKAR2), and upregulation of genes coding for enzymes from the amino acid biosynthetic pathways (HwMET6, HwMET14, HwMET17, HwSAM2, HwGDH1) and transport (HwAGP1; Vaupotič and Plemenitaš, 2007a).

The abundance of mitochondrial enzymes among the proteins involved in adaptation to loftier salinity indicated the of import role of the mitochondria in the farthermost halotolerance of H. werneckii (Vaupotič and Plemenitaš, 2007a). Indeed, with subcellular fractionation, we found that the quantity of the isolated mitochondria was at least twofold greater in cells exposed to hyperosmolar conditions. Observations of living cells stained with Mitotracker Light-green showed that both the ionic and nonionic osmolytes as well affected the distribution of the mitochondria (Vaupotič et al., 2008), which is a typical feature of agile organelle biogenesis (Westermann, 2002). In the hypersaline medium, this was accompanied by increased ATP synthesis and oxidative damage protection, whereas adaptation to the nonionic osmolyte resulted in a decrease in ATP synthesis and lipid peroxidation levels in mitochondria. A proteomic study of the mitochondria has revealed that the mitochondrial proteome remains in an agile respiratory and energy state when H. werneckii grows in hypersaline medium (Kar2, Pdi1, NADH-ubiquinone oxidoreductase, V-type H+-translocating pyrophosphatase, efflux transporter of RND family, putative lipoprotein, and mitochondrial aconitase), whereas growth in high sorbitol medium was mainly characterized by the accumulation of molecular chaperones (ATP-synthase beta subunit, Hsp60, Hsp70Kar2, Hsp60; Vaupotič et al., 2008). Thus, it appears that the basic metabolic network is constitutively working to meet the demands of the increased energy expenditure needed to maintain the ionic and osmotic homeostasis in a changing hyperosmolar surroundings.

Read total affiliate

URL:

https://www.sciencedirect.com/scientific discipline/article/pii/B9780123870445000030

Volume 1

Bernard Robaire , Barry T. Hinton , in Knobil and Neill's Physiology of Reproduction (Quaternary Edition), 2015

Sperm Protection

Information technology is clear that the claret–epididymis bulwark allows for the product of a specialized luminal fluid microenvironment that is important for sperm maturation. However, another critical role played by this barrier is protection of the maturing spermatozoa. In addition, a series of elaborate defense mechanisms that help to protect spermatozoa from the immune organisation, harmful xenobiotics and reactive oxygen species have been developed in the epididymis. The defense force mechanisms include restricting the types of compounds that tin enter the epididymal lumen, the synthesis and secretion of specific proteins such as the defensins and defensin-similar molecules, rapid elimination of potential harmful agents through the synthesis and secretion of antioxidant and conjugating enzymes, and the synthesis and secretion of antioxidant compounds such as glutathione and taurine. Because spermatozoa mature in a hyperosmotic environment, the epididymis too ensures that the spermatozoa are protected from potential rapid changes in osmolality and that spermatozoa can regulate their cell volume.

By 1950, information technology was shown that spermatozoa are highly susceptible to oxidative impairment and that hydrogen peroxide was responsible for loss of move and cell death. 434,435 Through a series of well-designed studies, Jones et al. clearly showed that when spermatozoa were incubated under aerobic atmospheric condition, they produced an organic peroxide and released a substance that was believed to exist a lipid. 436–439 When incubated in the presence of lipid peroxides, spermatozoa became irreversibly immotile and released numerous intracellular enzymes. From these series of studies, information technology was suggested that incubation of spermatozoa under aerobic atmospheric condition resulted in lipid peroxidation past peroxides and/or lipid radicals that were responsible for structural damage, loss of movement, decline in metabolic action and release of intracellular enzymes. Since mammalian spermatozoa take a loftier content of polyunsaturated fat acids in their membranes, they are highly susceptible to lipid peroxidation by reactive oxygen species (ROS). 438–441 Information technology is crucial that spermatozoa be protected from the deleterious effects of too high a product of ROS as they progress forth the epididymal duct; lipid peroxidation of membranes has been correlated with mid-piece defects, 442 decreased motility due to axonemal defects and reduced intracellular ATP levels, 443–445 as well as impaired chapters for fertilization (reviewed in Refs 442,446). In that location exists a delicate balance between the formation of ROS needed for sperm part and production of as well much ROS that will damage sperm membranes and DNA Spermatozoa can protect themselves from ROS via the presence of superoxide dismutase, catalase, glutathione peroxidases, glutathione transferases, and other enzymes regulating the balance between the production and elimination of ROS. 445–448 These enzymes protect spermatozoa from lipid peroxidation past ROS via dismutation of the reactive oxygen to hydrogen peroxide and h2o; hydrogen peroxide is and so speedily converted to h2o via the enzymes catalase and/or glutathione peroxidase; alternatively it is conjugated to glutathione. 442,446,449–453

In a continuing effort to prevent the oxidative harm to spermatozoa, the epididymis has developed an elaborate system to ensure that spermatozoa are protected as they mature along the epididymal duct. Each region or segment of the epididymis has developed its ain sperm protective mechanisms primarily because (1) the metabolic action differs from one region to the next, thereby producing different ROS species that need to be eliminated appropriately, and (two) spermatozoa are in a dissimilar state of maturity in each region, and therefore differ with respect to susceptibility to oxidative damage. For example, spermatozoa need to be especially protected from ROS as they enter the initial segment. The luminal fluid in this region is highly oxygenated, 454 the epithelial cells are surrounded by a dense capillary network, 455 with blood flow exceeding that of the distal epididymal regions, 456,457 and the initial segment cells are highly metabolically active (reviewed in Ref. 458). This unique combination results in the generation of ROS from several sources, including the endothelial and initial segment epithelial cells (reviewed in Refs 442,446). Therefore, it is non surprising that the initial segment expresses antioxidant enzymes. In the distal epididymal regions, the epithelial cells are still metabolically agile, and the spermatozoa are continually exposed to an oxygen-rich environment; however, the degree of vascularization is less compared to the initial segment. Hence, spermatozoa are still subjected to ROS production, but the type of ROS may well exist unlike from the types produced in the initial segment. Hence, the distal epididymal regions have alternative strategies to protect spermatozoa.

The major antioxidant enzymes present in the epididymis include superoxide dismutase, 459,460 gamma-glutamyl transpeptidase, 461–466 glutathione peroxidases, 467–471 glutathione transferases, 167,472–475 peroxyredoxins, 475–478 and indoleamine dioxygenase. 479 In add-on, the lumen of the epididymis contains antioxidant molecules including glutathione, taurine, and tryptophan every bit the substrate for indolamine dioxygenase. Each of these antioxidant enzymes and molecules is institute to varying degrees throughout the length of the epididymis.

Hence, the epididymis plays a disquisitional role in the protection of spermatozoa from oxidative stress and from harmful xenobiotics. Interestingly, the processes by which the epididymis protects spermatozoa accept also been considered to be a prime target for the development of a male contraceptive. 442

Read full chapter

URL:

https://www.sciencedirect.com/science/commodity/pii/B978012397175300017X

International Review of Cell and Molecular Biological science

Frank P. Conte , in International Review of Cell and Molecular Biology, 2012

iii Salinity Adaptation in Development of Opercular/Skin Epithelium versus Filamental Gill Epithelium

The dynamics of basolateral membranes involve many types of membrane kinases. Marshall et al. (2005) observed the disappearance of CFTR from the subapical locus of vesicles past immunocytochemistry and it apparently was part of the rapid turnover (<1   h) by apical catacomb components used in the recycling mechanism. It was believed that de novo synthesis of protein components in these vesicles by transcriptional and translational processes could not have occurred due to time restraints. However, serum and glucocorticoid-inducible kinase-one was shown to be in some manner involved in this mechanism simply as all the same non be resolved. Details of the mechanism of membrane kinases with Golgi have not been made in fish. However, recent studies on membrane kinases in Golgi apparatus taken from mammalian clones take shown that receptor tyrosine kinases function every bit key regulators in the trafficking of membrane components between Golgi and the basolateral tubular network (Charest et al., 2003). In conflict with the higher up estimation, in that location are data obtained from other euryhaline species: coho salmon, tilapia, and guppy, that proteomic ion pumps needed for table salt excretion are made by the mechanism of protein synthesis. This protein synthesis machinery had been a focus for early investigations. It was shown that SW fish had increased levels of polyribosomes and tyrosinyl- and aspartyl-transfer RNA (Conte and Murray, 1973: Conte, 1976) and elevated levels of protein biosynthesis (Tondeur and Sargent, 1979) and enzymatic poly peptide abundance (Tang and Lee, 2007 ). These results propose that gill filamental IC were making new proteins and kinetic assay indicated that it takes more than 1 week to be completed. The evidence that hypo- and hyperosmotic environments initiate cues for ii different osmotic receptors supports the hypothesis that ii developmental pathways may exist in gill filamental epithelium. The most recent bear witness for the existence of ii pathways was obtained using new tools of molecular genetics, such as in translational factor knockout techniques and immunocytochemistry to unravel the role of protein pump domains necessary for maintaining ionic and osmotic rest in the embryonic fish. Hwang and Lee (2007) using antibodies to isoform subunits of Na,Chiliad-ATPase, coupled co-transporter NKCC and chloride aqueduct transporter CFTR for seawater fish and in FW-fish, the isoform subunits of vacuolar H+-ATPase, NHE2 and NHE3 sodium ion uptake, together with carbonic anhydrase complex. It was shown that extrabranchial stem cells (IB) were found to exist in various populations of differentiated flick and in the completely functional (aqIC or haIC). Based upon these data, they interpreted that the extrabranchial stem cells (IB) are responsible for at to the lowest degree three subpopulations of mature IC: (1) Na pump type with apical calcium channel or NaRC IC, (2) proton pump type with acid secretion connected with carbonic anhydrase circuitous and sodium uptake or HRC IC, and (3) Co-transporter of sodium-potassium and chloride assimilation or NCC IC (Fig. 1.3).

Figure 1.3. Model of IC differentiation in dissimilar FW species. In Zebrafish type, at that place are four cell types. For details run across Section 7 in the text.

 Ref.Hwang et al. (2011).

The skin/opercular IC contain all the molecular mechanisms which announced to be responsible for acid-base regulation in the early embryonic pre-gill larval stages while the embryo resides in FW. Later, Hiroi et al. (2005) using immunofluorescence staining for ion ship enzymes, such as Na/Grand-ATPase, NKCC and CFTR, institute that intracellular localization of these 3 enzymes would yield four types of IC in tilapia embryos (Figs i.iv and 1.5).

Effigy 1.4. Model of IC differentiation in Tilapia. Schematic diagram of the four MRC types, showing intracellular localization of the ion transporters for command of ionic movements within the cell. For details run across Section 7 in the text.

 Ref.Hiroi et al. (2005).

Effigy one.5. Model of the four types of MRCs every bit shown in Fig. 1.four and their presumptive interrelationships. These motion-picture show would and then lead to mature IC which would be found in filamental epithelium of fish residing in either FW conditions or seawater conditions. For details refer to Section vii in the text. Ref. Hiroi et al. (2005) . For color version of this figure, the reader is referred to the online version of this book.

Type I jail cell was a nonfunctional immature pIC. Blazon Two cell was a FW HRC using a proton pump in the formation of an ion absorption cell. Type III cell was a prototype and/or fallow type (pIC) of the salt secretory prison cell (NaRC). Type IV was the agile seawater-secreting NaRC containing the sodium pump and chloride channel which handle the movement of sodium and chloride ions. Since the classification of these four types of cells were obtained from embryonic tissue, the consequence of whether the filamental IC only come from embryonic stem cells (IB) which are differentiated into migrating flick that locate in the interlamellar region and become mature IC or does the Type I and Type Iii come from a dormant form of a progenitor (pIC) and can deed as an developed stem cell. It is an important aspect in our understanding of how the integrative and regulatory physiology of transepithelial ion transport in teleost fishes takes identify. Because, as was shown before, the time course data in seawater adaptation are under the influence of apoptosis factors that control destruction of differentiating picture show that permit the full induction of the adult stem cells to have place which is 5 days in length. This delay appears to provide the needed jail cell population of mature haNaRC for long-term adaptation. Can the initiation of apoptosis act upon surface receptors of non-NaRC or HR IC prototypes and cause their intrinsic decease? Recently, Nguyen et al. (2006) studying the interaction between SPAK p63 and Notch-one genes found that summit of p63 counteracts the power of Notch-1 genes to promote growth and differentiation of epithelial cells. Therefore, circuitous cantankerous talk between these gene families could change the selective inhibition of apoptotic factors. This genetic pathway becomes very important in the coordination of the various genes that provide regulatory processes for osmotic and ionic remainder in fish body fluids.

Read full chapter

URL:

https://www.sciencedirect.com/science/commodity/pii/B9780123943101000011

Catheter Ablation

Eric Buch , ... Kalyanam Shivkumar , in Cardiac Electrophysiology: From Prison cell to Bedside (Seventh Edition), 2018

Cryoablation

Cryoablation employs extreme cooling to damage myocardial tissues and create nonconductive ablation lesions. The offset awarding of cryoablation in the treatment of arrhythmia was described by Klein and colleagues for the epicardial ablation of accessory pathways using a surgical approach. 33 After intraoperative mapping localized the accessory pathway, a cryoprobe cooled to −60°C was applied to the target site to ablate the pathway.

Endovascular cryoablation systems use a steerable ablation catheter that tin be cooled to −70°C or lower, resulting in tissue necrosis with a like lesion size to that attained with irrigated RF ablation catheters. 34 Commercially available systems absurd the catheter tip by delivering nitrous oxide under pressure via a hollow injection tube that spans the length of the ablation catheter into a widened lumen at the catheter tip. Nitrous oxide expands and decompresses inside a small chamber at the catheter tip, resulting in cooling based on the Joule-Thomson consequence. The cooled catheter and so extracts heat from the tissue in contact with the distal electrode. 35 Similar to RF catheters, cryoablation systems tin monitor tip temperature and accommodate refrigerant period to maintain a specified temperature.

Lesion formation in cryoablation occurs through direct cellular injury and vascular-mediated tissue injury. Direct injury results from ice formation, resulting in a hyperosmotic environs that causes cells to shrink and amercement the plasma membrane. Irreversible cellular injury can also occur in the rewarming phase. Cooling myocardial tissue to temperatures depression enough to result in extracellular water ice germination causes cellular death when practical for prolonged periods. Still, when only briefly cooled to this temperature, nigh jail cell harm is reversible, and cellular function usually recovers without permanent damage. This makes it possible to deliver a functionally reversible lesion in many cases. A technique referred to equally cryomapping is accomplished by cooling tissue to −30°C for 30–60 seconds to identify transient physiological changes, such as abolition of accessory pathway conduction or prolongation of the A-H interval. 36 If cryomapping achieves the desired result without signs of collateral damage, a cryoablation lesion is delivered at the aforementioned location by maintaining a tissue–catheter tip interface temperature below −50°C for 4 minutes, resulting in irreversible tissue destruction. Another useful feature of cryoablation is catheter stability during ablation, resulting from cryoadhesion of catheter to tissue resulting from ice formation.

In addition to direct tissue injury, cryoablation besides results in lesion formation via vascular-mediated tissue necrosis. Initially, the awarding of cryothermal energy results in decreased perfusion from vasoconstriction. When tissue temperature drops to beneath freezing, circulation ceases, resulting in tissue harm via ischemic necrosis, every bit well as endothelial harm, platelet assemblage, and microthrombus formation. Afterwards, rewarming of frozen tissue causes hyperemia, with increased vascular permeability and edema.

In catheter-based focal cryoablation systems, the coldest area is adjacent to the catheter tip, and the effects are outset observed at these sites. Farther abroad, at the periphery of the cryoablation lesion, cooling is delayed and of a lower magnitude, ofttimes resulting in reversible tissue impairment. Thus furnishings noted late during the awarding of cryoenergy are less probable to be permanent and may contrary upon rewarming. In general, ablation success is correlated with early functional modification, commonly within 30–sixty seconds of cryoenergy application.

Cryoenergy has been used in several different forms for myocardial lesion formation to treat cardiac arrhythmias. In surgical AF ablation, epicardial cryoenergy can be applied to isolate PVs. 37 Ventricular arrhythmias take besides been treated with epicardial cryoablation. 38 Percutaneous endocardial catheter cryoablation is also used in the handling of arrhythmia. An early awarding of focal cryoenergy catheter ablation was slow pathway ablation in the handling of AV node reentrant tachycardia (AVNRT). Cryoablation is useful in this setting because of the proximity of the meaty AV node and concerns about iatrogenic AV block. In this or other high-adventure areas (eastward.thou., near the phrenic nervus, His bundle, or coronary avenue), cryomapping allows assessment of the safe of a potential ablation site before ablation causes permanent irreversible tissue impairment. A randomized comparison between cryoablation and conventional RF ablation for AVNRT showed equivalent acute success and no AV block in the cryoablation grouping but with a higher chance for recurrence (9.iv% vs. iv.four%). 39 The potential benefits of cryoablation over RF ablation must be weighed confronting the possibility of higher risk for recurrence and reoperation.

Another promising application of cryoablation is ablation of accessory pathways in high-hazard anatomical locations, such as nearly the native conduction system or inside the coronary sinus, in which application of RF energy carries a higher risk for complications. Concerns nigh durable efficacy persist; for accessory pathways located within the coronary sinus, Collins and colleagues reported only 71% acute success and 40% risk for recurrence. xl Cryoablation has besides been used in the treatment of typical correct atrial flutter, resulting in longer procedural times, similar acute outcomes, and improved patient tolerability. 41

Endocardial cryoablation is an increasingly mutual modality for PV isolation in the treatment of AF (Fig. 123.iii). In this arrangement, a catheter delivers nitrous oxide to an inner balloon, where it undergoes a phase alter resulting in a temperature drop to well-nigh −80°C. The balloon catheter has a central lumen for a screw mapping catheter to guide balloon position, reduce perforation run a risk, and tape PV potentials during ablation. Kinetics of tissue devastation are like to RF ablation, related both to proximity of targeted tissue to cryoballoon surface, and duration of energy application (Fig. 123.4). In a multicenter written report, 97% of 1403 PVs were acutely isolated using cryothermal energy delivered via a balloon catheter, and 1-year outcomes were similar to those observed with RF ablation. 42 The randomized STOP-AF trial found that cryoballoon ablation was more effective than antiarrhythmic drugs for rhythm command (70% vs. 7% success at i year) but with 11% hazard for transient or persistent phrenic nervus injury. 43 Besides phrenic nerve injury, other complications have been observed, including PV stenosis 44 and esophageal injury. 45 The second-generation cryoballoon, which uses multiple nitrous oxide jets to absurd the unabridged distal hemisphere of the balloon, is likely to exist more constructive but with greater potential for damage to side by side anatomical structures. 46,47 Electric current show suggests that cryoballoon and RF ablation accept like efficacy and safety for PV isolation with shorter procedure time, 48–50 recently confirmed in a large randomized study comparing the two approaches. 51

Read total affiliate

URL:

https://www.sciencedirect.com/scientific discipline/article/pii/B9780323447331001231

The MAP Kinase Network As the Nervous System of Fungi

I. Correia , ... E. Román , in Reference Module in Life Sciences, 2017

2.1 Pig Pathway: Sensing Environmental Stress

In C. albicans, the HOG pathway has been associated to many central processes such as morphogenesis, prison cell wall biogenesis, virulence, although predominantly, in the response and adaptation to stress (Alonso-Monge et al., 1999, 2003; Smith et al., 2004; Enjalbert et al., 2006). Recently, its role on C. albicans response to arsenate and arsenite has also been uncovered (Urrialde et al., 2015). In fact, the MAP kinase of the pathway Hog1 (homolog to Hog1 in the yeast S. cerevisiae) becomes activated in response to a variety of stimuli such as high osmolarity or oxidative stress, which occurs in a Pbs2-dependent manner (the pathway canonical MAPKK) through Ssk2 (MAPKKK) mediated signaling (Arana et al., 2005; Cheetham et al., 2007). The activation of the HOG pathway leads to glycerol accumulation (San José et al., 1996), equally occurs in South. cerevisiae (Albertyn et al., 1994 ), which counteracts prison cell dehydration acquired by hyperosmotic environments. The activation of this route upon oxidative stress ( Alonso-Monge et al., 2003) is of special importance in C. albicans as it constitutes a blazon of stress probably more related to the environment this fungus encounters during its life cycle within the host. Translocation of Hog1 to the nucleus due to oxidative stress generates an adaptive transcriptional response which is partially overlapping, although distinguishable, from the one generated by the transcription factor Cap1 (Alonso-Monge et al., 2003; Enjalbert et al., 2006), homologue of ScYap1 in C. albicans and shown to play a function in multidrug and oxidative stress resistance (Alarco and Raymond, 1999; Zhang et al., 2000). Farnesol and caspofungin have been likewise described to activate Hog1 (Bamford et al., 2009; Kelly et al., 2009), indicating that both treatments induce oxidative stress in this fungus which is sensed by the HOG pathway. The downstream molecular mechanisms that underlie Hog1-mediated oxidative stress resistance remain an expanse of active enquiry. The transcriptional repressor Sko1 mediates in role this oxidative response (Alonso-Monge et al., 2010).

In S. cerevisiae, the HOG pathway is activated upon osmotic stress via two different upstream branches: the SLN1-branch which is a two-component system relying on SLN1, YPD1 and SSK1 genes to mediate the activation of the functionally redundant Ssk2/Ssk22 MAPKKKs; and the SHO1-branch, the 2d input of this cascade, which converges at the Pbs2 MAPKK through the Ste20 PAK-like kinase (Posas et al., 2000; de Nadal et al., 2002; Hohmann, 2002). In dissimilarity, although both branches practise exist in C. albicans, only the orthologues of the mentioned genes for the SLN1-branch mediate the activation of Hog1 past oxidative stress (Chauhan et al., 2003; Cheetham et al., 2007). The C. albicans SHO1-branch is non involved in the activation of Hog1 but rather in the activation of Cek1, a homolog of the South. cerevisiae KSS1, upon osmotic stress (Román et al., 2005). Deletion of upstream components of this pathway (mediated by Cek1), in combination with SSK1, does not impair activation of Hog1 or glycerol accumulation in response to osmotic stress, although cells remain sensitive to high osmolarity. Thus, although the SHO1-branch participates in the response to osmotic and oxidative stress, it does and so through HOG1-independent mechanisms (Román et al., 2005; Román et al., 2009a). Integration of the oxidative stress response is, however, a complex procedure and the precise connections between the HOG pathway and other routes and oxidative defense mechanisms remain to exist determined (Komalapriya et al., 2015).

It has been likewise described the implication of the Squealer pathway in dissimilar morphogenetic programs also as in the biogenesis of the cell wall. Strains defective genes from this signaling cascade such as hog1, pbs2 or ssk2 display enhanced truthful hyphal formation as evidenced nether non-inducing conditions (Alonso-Monge et al., 1999; Arana et al., 2005; Cheetham et al., 2007). In contrast, ssk1 mutants show a reduced ability to filament even in the presence of serum, a phenotype that is not suppressed by HOG1 overexpression (Alex et al., 1998; Calera et al., 2000). This is partially achieved via the activation of the Cek1-pathway (Eisman et al., 2006), which promotes filamentation in this fungus. In addition, the Brg1 transcription factor and a positive regulator of filamentation, is expressed in hog1, pbs2 and ssk2 mutants independently of rapamycin, an activator of the TOR pathway, therefore suggesting that the TOR pathway is involved in hyphal elongation via the Hog pathway (Su et al., 2013). Interestingly, sko1 mutants, which are sensitive to oxidative stress and increase damage in hog1 mutants, display increased filamentation (Alonso-Monge et al., 2010). In addition to the yeast-to-hypha transition, Hog1 is also essential for chlamydospore formation, interim independently from Efg1 which was the first regulatory factor shown to be involved in this developmental procedure (Sonneborn et al., 1999). Both efg1 and hog1 are unable to form chlamydospores and overexpression of EFG1 gene in a hog1 mutant – and vice versa – did non restore the phenotype (Alonso-Monge et al., 2003). Other genes that control chlamydospore development accept been uncovered (Staib and Morschhauser, 2007). The Hog1 MAPK has been recently linked to another morphogenetic program in C. albicans, the white–opaque switching. In lodge to mate, homozygous cells for the MTL need to undergo an epigenetic switch from the standard white phenotype to the opaque and mating-competent country. The activation of the Squealer pathway seems to be crucial for this process as the absence of Hog1, Pbs2 or Ssk2, besides as point mutations at the conserved phosphorylation sites of Hog1, increases the switching frequency and suppresses mating and pheromone-stimulated prison cell adhesion (Liang et al., 2014; Chang et al., 2016).

Regarding jail cell wall biogenesis, it was originally described that the deletion of hog1 confers a resistant phenotype to certain compounds such as nikkomycin Z (which inhibits chitin synthesis) and Congo ruddy or calcofluor white which change the correct cell wall associates (Alonso-Monge et al., 1999; Román et al., 2005). It has been proposed, based on transcriptional studies, that the HOG pathway regulates chitin synthesis coordinately with other pathways (Munro et al., 2007). This could involve other MAPKs, such as Cek1, which has been also shown to exist of import in cell wall germination (Navarro-García et al., 2005; Eisman et al., 2006).

The Squealer pathway as well mediates metabolic adaptation in C. albicans. In fact hog1 mutants are hypersensitive to inhibitors of the respiratory chain similar azide and display an increased basal respiration, indicating that hog1 mutants are more dependent on mitochondrial ATP synthesis (Alonso-Monge et al., 2009a). Kaba and coworkers take farther described a transient Hog1 phosphorylation under high atomic number 26 concentrations, essential for the flocculent phenotype observed in a wild blazon strain, and a loss of viability of the hog1 mutant when exposed to high concentrations of fe (Kaba et al., 2013).

Since the Sus scrofa pathway plays and then many crucial roles in the biology of C. albicans, it is non surprising the relevance of this pathway in fungal pathogenesis. In fact, though hog1 mutants are hyperfilamentous (therefore, expecting to crusade increased tissue damage), they prove an attenuated virulence in a mouse model of systemic infection (Alonso-Monge et al., 1999). A phenotype of hog1 mutants that could explain this is their sensitivity to oxidative and nitrosative stress, even more than pronounced in pbs2 strains (Arana et al., 2005). This could result in sensitivity to the phagocytic attack by macrophages and neutrophils which generate ROS or reactive nitrogen species (RNS) to permit fungal clearance (Missall et al., 2004; Du et al., 2005; Arana et al., 2007). In add-on, strains with a compromised HOG pathway are hypersensitive to some antimicrobial peptides such as the salivary cationic peptide histatin-v (Hst 5) (Vylkova et al., 2007) and β-defensins ii and iii (Argimon et al., 2011). Hog1 (and Pbs2) take been too shown to play a critical role in the establishment of C. albicans in the mouse gut (colonization) which could exist explained past their decreased adherence to the gut mucosa and/or sensitivity to bile salts (Prieto et al., 2014).

Read full chapter

URL:

https://www.sciencedirect.com/science/article/pii/B9780128096338120941

Enzymes involved in osmolyte synthesis: How does oxidative stress affect osmoregulation in renal cells?

Jesús A. Rosas-Rodríguez Elisa M. Valenzuela-Soto , in Life Sciences, 2010

Oxidative stress in the renal medulla

The chief sources of reactive oxygen species in the renal medulla are hyperosmolality, NADH oxidase activity and the mitochondrial respiratory chain. Medulla cells are surrounded by a hyperosmotic environment considering an osmotic gradient is needed for water reabsorption to occur during the urinary concentrating mechanism. Zhang et al. (2004) establish testify which suggests that the medulla cells are ordinarily nether oxidative stress.

Superoxide concentration is high in renal cells, and superoxide is so converted to hydrogen peroxide by superoxide dismutase (Harper et al. 2004; Zou et al. 2001). In addition, ROS concentration is influenced past endogenous (metabolism, direct and indirect producing ROS enzymes, and diseases) and exogenous factors (radiation, toxins, and food) (Kohen and Nyska 2002; Nohl et al. 2005).

Loftier ROS levels play a role in a diversity of renal diseases such equally glomerulonephritis and tubulointerstitial nephritis, renal insufficiency, proteinuria and hypertension, also as contributing to the pathogenesis of ischemia reperfusion injury in the kidney (Martin and Goeddeke-Merickel 2005; Vaziri 2004). The relationship betwixt ROS and renal diseases shows that kidney is particularly sensitive to ROS.

In kidney, ROS are kept at low concentrations and office equally signalling molecules that maintain vascular integrity by regulating endothelial function and vascular wrinkle (Touyz 2004). Notwithstanding, the molecular events that increase the reactive oxygen species during stress, such as osmotic stress, are not completely understood (Kültz 2004). In many types of stress, the action of some proteins increases in order to alert other systems. Cellular oxidases such as NADPH oxidase are very quickly activated, which may explicate increased in ROS levels (about 0.1   mM in injured tissue). In this case, ROS and cellular redox potential function as cellular stress response signals (Kültz 2005). Among ROS, attention has been focused on the free radical superoxide anion, which is highly reactive, and the more than stable hydrogen peroxide (H2O2). The reaction of HtwoO2 leads directly to the formation of the highly reactive hydroxyl radical and has been implicated in endothelial dysfunction (Wilcox 2005).

Medulla cells have antioxidant enzymes (MnSOD, CuZn-SOD, glutathione peroxidase, and catalase), scavenging antioxidants and metal-binding proteins to avoid the deleterious furnishings of ROS. In addition, osmolytes such every bit glycine betaine, glycerophosphocholine and inositol (Fig. 1), amongst others, are good candidates for playing a part in the oxidative stress response machinery. However, the imbalance betwixt the antioxidant arrangement and oxidant generation, as upshot of diabetes, hypertension, constant high osmolarity, etc., results in a renal damage.

Identifying the proteins that are susceptible to oxidative damage in cellular stress response molecules could lead to a meliorate understanding of the complexity of the alterations acquired by oxidative stress, and allow us to counteract the injury acquired past ROS.

Read full article

URL:

https://www.sciencedirect.com/scientific discipline/article/pii/S0024320510003504

Advances in Barrett's Esophagus

Charlotte N. Frederiks Physician , ... Bas L.A.Grand. Weusten MD, PHD , in Gastrointestinal Endoscopy Clinics of North America, 2021

Background and principles of cryotherapy

Cryotherapy is an ablative modality triggering tissue destruction through the repetition of rapid cooling and ho-hum thawing (freeze-thaw bike). 6 3 major mechanisms of activeness are involved in the destructive changes caused past cryotherapy.

The first machinery of activeness comprises direct cell injury mediated by ice crystal formation. Initially, extracellular ice crystal formation generates a hyperosmotic environment, resulting in cell dehydration through water extraction from the cells. Later, intracellular ice crystals are formed which disrupt organelles and prison cell membranes. During thawing disturbances in the osmotic slope crusade water to reenter the damaged cells promoting membrane rupture. 7 This deleterious cascade eventually leads to prison cell expiry inside hours to days. half-dozen

Jail cell death is further affected within hours to days past the induction of apoptosis, the 2nd mechanism of action. eight Apoptosis results from the activation of an extrinsic rapid membrane-related apoptotic pathway in the cadre of the cryogenic lesion, and intrinsic delayed mitochondrial damage in the peripheral zone of the cryogenic lesion, partly due to severe oxidative stress. vi

The third mechanism of action consists of the failure of microcirculation and vascular stasis, over days to weeks. half dozen At first freezing of tissue induces vasoconstriction and stagnation of the blood menstruum. After thawing of the tissue the circulation is restored with vasodilation propagating endothelial damage. seven This endothelial damage facilitates edema, platelet aggregation and microthrombus formation, ultimately leading to tissue ischemia and secondary necrosis. eight

Multiple factors contribute to the degree of cell injury, including the number of the freeze-thaw cycles, the duration of freezing, and the achieved nadir tissue temperature. 6 , viii , nine Although it has been demonstrated that a temperature below −50°C sufficiently induces prison cell expiry in a single freeze-thaw wheel, cycles are typically repeated to heighten the lethal issue. 8 , 9 Nevertheless, the exact dosimetry of cryotherapy remains challenging due to the heterogeneity in application techniques and device types, and variability within the target tissue. 6

Cryotherapy holds several potential advantages over heat-based ablation techniques, such as radiofrequency ablation (RFA) and argon plasma coagulation (APC). In contrast to cryotherapy, heat-based techniques induce denaturation of (extracellular) structural proteins leading to irreversible changes in poly peptide construction. With cryotherapy, the extracellular matrix compages is believed to be preserved. half-dozen Specifically for the esophagus, this preservation might enable deeper ablation without increasing the hazard of stricture germination. Furthermore, cryotherapy might have a favorable tolerability due to directly effects of the cold. For example, in patients with renal tumors less sedation and analgesia medication were required during cryotherapy compared to RFA. 10 , 11 Besides, lower hurting levels were associated with cryotherapy in patients treated for atrioventricular reentrant tachycardia. 12 Potential underlying mechanisms previously described include an anesthetic effect on the tissue, and the inactivation of nerve conduction. thirteen

Read total article

URL:

https://www.sciencedirect.com/scientific discipline/article/pii/S1052515720301057