scholarly journals Bacterial Burden Declines But Neutrophil Infiltration and Ocular Tissue Damage Persist in Experimental Staphylococcus epidermidis Endophthalmitis

2021 ◽  
Vol 11 ◽  
Author(s):  
Susmita Das ◽  
Sukhvinder Singh ◽  
Ashok Kumar
Keyword(s):  
Tissue Damage ◽  
Visual Function ◽  
Time Course ◽  
Bacterial Load ◽  
Experimental Studies ◽  
Neutrophil Infiltration ◽  
Ocular Tissue ◽  
Bacterial Burden ◽  
Similar Time

Coagulase-negative staphylococci (CoNS), including Staphylococcus (S) epidermidis, are responsible for ~70% of all post-surgical endophthalmitis, a potentially blinding eye infection. However, the pathobiology of CoNS endophthalmitis is limited to epidemiological and clinical case studies with few experimental studies. Here, we report both in vitro and in vivo models to study the pathobiology of S. epidermidis endophthalmitis in mice. We found that S. epidermidis is rapidly cleared from mouse eyes, and a relatively higher dose (i.e., 107 CFU/eye) was needed to cause endophthalmitis. Our time-course study revealed that bacterial load peaked at 24 h post-infection followed by a gradual decline up to 72 h. A similar time-dependent decrease in levels of inflammatory mediators and Toll-like receptor (TLR) expression was also observed. In contrast, neutrophil infiltration continued to increase up to 72 h coinciding with significant retinal tissue damage and loss of visual function. In vitro, S. epidermidis induced the activation of various inflammatory signaling pathways (i.e., NF-kB, ERK, and P38) and the production of both cytokines and chemokines in mouse BMDMs, human RPE, and retinal Muller glia. Altogether, we show that bacterial burden is reduced in S. epidermidis endophthalmitis, while tissue damage and visual function loss continue. Thus, our study provides new insights into the pathogenesis of CoNS endophthalmitis.

Liver X Receptor Activation Impairs Neutrophil Functions and Aggravates Sepsis

2019 ◽  
Vol 221 (9) ◽  
pp. 1542-1553 ◽  
Author(s):  
Fabrício O Souto ◽  
Fernanda V S Castanheira ◽  
Silvia C Trevelin ◽  
Braulio H F Lima ◽  
Guilherme Cesar Martelossi Cebinelli ◽  
...  
Keyword(s):  
Multiorgan Failure ◽  
Bacterial Load ◽  
Cecal Ligation ◽  
Neutrophil Infiltration ◽  
Receptor Activation ◽  
Messenger Ribonucleic Acid ◽  
X Receptors ◽  
Lxr Agonists

Abstract Background Liver X receptors (LXRs) are nuclear receptors activated by oxidized lipids and were previously implicated in several metabolic development and inflammatory disorders. Although neutrophils express both LXR-α and LXR-β, the consequences of their activation, particularly during sepsis, remain unknown. Methods We used the model of cecal ligation and puncture (CLP) to investigate the role of LXR activation during sepsis. Results In this study, we verified that LXR activation reduces neutrophil chemotactic and killing abilities in vitro. Mice treated with LXR agonists showed higher sepsis-induced mortality, which could be associated with reduced neutrophil infiltration at the infectious foci, increased bacteremia, systemic inflammatory response, and multiorgan failure. In contrast, septic mice treated with LXR antagonist showed increased number of neutrophils in the peritoneal cavity, reduced bacterial load, and multiorgan dysfunction. More important, neutrophils from septic patients showed increased ABCA1 messenger ribonucleic acid levels (a marker of LXR activation) and impaired chemotactic response toward CXCL8 compared with cells from healthy individuals. Conclusions Therefore, our findings suggest that LXR activation impairs neutrophil functions, which might contribute to poor sepsis outcome.

EVIDENCE FOR GRANULOSA-THECA INTERACTION IN THE SECRETION OF OXYTOCIN BY BOVINE OVARIAN TISSUE

1986 ◽  
Vol 109 (1) ◽  
pp. R1-R4 ◽  
Author(s):  
B. Jungclas ◽  
M.R. Luck
Keyword(s):  
Time Course ◽  
Ovarian Tissue ◽  
Time Frame ◽  
Follicular Cells ◽  
Similar Time ◽  
Follicular Maturation ◽  
Progesterone Secretion ◽  
Theca Interna ◽  
Predetermined Time

ABSTRACT We have examined the ability of granulosa cells, from carefully selected preovulatory bovine follicles, to secrete oxytocin in vitro. Although cells from 83% of follicles underwent functional luteinisation (greatly increased progesterone secretion) in serum-supplemented culture, only 69% had cells capable of oxytocin secretion. Secretion followed a similar time course in all cultures, with the peak appearing on day 3. Oxytocin, but not progesterone, output could be consistently increased by addition of pieces of theca interna tissue, or theca conditioned medium, to the cultures. The effect could be achieved by exposure to theca tissue at any time prior to peak output without altering the time course of secretion. Oxytocin could not be detected in follicular fluid from any of the selected follicles, nor in medium from theca cultured alone. We conclude that the potential for oxytocin secretion is a feature of follicular maturation which is lost during atresia and that the stimulus to secretion is associated with luteinisation but not with progesterone output. Finally, the intermixing of follicular cells during corpus luteum formation may provide a mechanism for the enhancement of oxytocin secretion within a predetermined time frame.

Afterdepolarization mechanism in the in vitro, cesium-loaded, sympathetic preganglionic neuron of the cat

1987 ◽  
Vol 57 (5) ◽  
pp. 1325-1337 ◽  
Author(s):  
M. Yoshimura ◽  
C. Polosa ◽  
S. Nishi
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Time Course ◽  
Choline Chloride ◽  
Membrane Potentials ◽  
Ca Channel ◽  
Krebs Solution ◽  
Similar Time ◽  
K Concentration

Intracellular recordings were performed in Cs-loaded sympathetic preganglionic neurons (SPNs) of the intermediolateral nucleus, identified by antidromic stimulation, in the slice of the T2 or T3 segment of the cat spinal cord. Loading the neurons with Cs resulted in broadening of the action potential, depression of the fast component of the afterhyperpolarization (AHP), and appearance of an afterdepolarization (ADP). A typical ADP in a Cs-loaded neuron had time to peak of 45-110 ms, half-decay time of 70-250 ms, and amplitude of 2-10 mV at membrane potentials between -60 and -70 mV and at a Ca and K concentration of 2.5 and 3.6 mM, respectively, in the superfusion medium. The ADP was associated with a decrease in neuron input resistance and increased in magnitude with hyperpolarization of the cell membrane. The relation between peak ADP amplitude and membrane potential was linear within the range of membrane potentials from -60 to -100 mV. The ADP was reversibly suppressed by the Ca-channel blocker cobalt (2 mM) or by low Ca Krebs solution (0.25 mM). Superfusion with BaCl2 (1.0 mM) or tetraethylammonium (TEA) (10-20 mM) caused an increase in amplitude of the ADP and an increase in action potential duration. Hyperpolarizing pulses, delivered during the course of the spike shoulder, resulted in a decrease of spike duration and ADP amplitude. The ADP was not affected by tetrodotoxin, at a dose blocking the Na-spike, and was enhanced, in association with an increase in action potential duration, when NaCl in the Krebs solution was replaced with choline chloride. Increasing intracellular Cl concentration or decreasing extracellular Cl concentration had no effect on the ADP. Changes in external K concentration from 3.6 to 10 or 0.36 mM increased and decreased, respectively, the amplitude of the ADP. In the absence of Cs, and ADP, with similar time course to that recorded in Cs-loaded SPNs, was recorded when CaCl2 was replaced by BaCl or NaCl was replaced by TEAC1. It is concluded that the SPN afterpotential includes a Ca-dependent inward current, in addition to the already described fast and slow outward K currents of the AHP.

Antioxidant supplementation enhances bacterial peritonitis in mice by inhibiting phagocytosis

2014 ◽  
Vol 63 (3) ◽  
pp. 355-366 ◽  
Author(s):  
Manish Goswami ◽  
Deepak Sharma ◽  
Nazir M. Khan ◽  
Rahul Checker ◽  
Santosh Kumar Sandur ◽  
...  
Keyword(s):  
Oxidative Burst ◽  
Bacterial Load ◽  
Neutrophil Infiltration ◽  
Peritoneal Macrophages ◽  
Antioxidant Supplementation ◽  
E Coli ◽  
Bacterial Peritonitis ◽  
Therapeutic Advantage ◽  
Tnf Α

Antioxidants are known to exhibit numerous health benefits including anti-ageing, anti-apoptotic and immuno-stimulatory effects. However, we present the data showing counterproductive effects of therapeutically relevant antioxidants on bacterial clearance by the immune system in a murine peritonitic model. The antioxidants ascorbic acid, glutathione and N-acetylcysteine augmented morbidity and mortality in mice carrying Eshcerichia coli-induced acute bacterial peritonitis. Treatment of peritonitic mice with antioxidants significantly increased their bacterial load in the range of 0.3–2 logs. Antioxidant administration to peritonitic mice resulted in decreased numbers of macrophages, B-cells and dendritic cells at the primary site of infection and increased neutrophil infiltration. Serum TNF-α levels were also decreased in antioxidant-treated peritonitic mice. In vitro experiments showed that antioxidants reduced the phagocytic efficacy of peritoneal macrophages by ~60–75 % and also decreased E. coli-induced oxidative burst in macrophages cells. Taken together, our data indicate that the antioxidants increased the severity of peritonitis by decreasing the phagocytic efficiency, oxidative burst, and TNF-α production, and increasing neutrophil infiltration. Based on these results, we propose that antioxidant supplementation during the course of bacterial infection is not recommended as it could be detrimental for the host. In addition, the present study underlines the importance of timing and context of antioxidant administration rather than indiscriminate usage to gain the best possible therapeutic advantage of these redox compounds.

scholarly journals STUDIES ON THE MECHANISM OF HYPERSENSITIVITY PHENOMENA

1957 ◽  
Vol 106 (6) ◽  
pp. 811-834 ◽  
Author(s):  
Abraham G. Osler ◽  
Mary M. Hawrisiak ◽  
Zoltan Ovary ◽  
Maria Siqueira ◽  
Otto G. Bier
Keyword(s):  
Time Course ◽  
Passive Cutaneous Anaphylaxis ◽  
Similar Nature ◽  
Similar Time ◽  
Partial Restoration ◽  
The Third ◽  
Antigen Antibody ◽  
Derivatives Of

Experiments are described indicating that the magnitude and sensitivity of the passive cutaneous anaphylaxis (PCA) response in normal rats to a given level of immune reagents, may be enhanced by the addition of hemolytically active sera. A similar enhancement in normal rats has been obtained with C' component reagents possessing properties associated with the third component of C'. Parallelisms between in vitro fixation of C' and PCA induction by antigen and antibody are shown. The horse anti-pneumococcus system has low C'-fixing potencies and is also less efficient than the rabbit polysaccharide system in the induction of PCA. Findings of a similar nature were observed in the reaction of rabbit anti-ribonuclease with ribonuclease, the acetylated and guanidinated derivatives of the enzyme. The injection of hemolytically active serum into C'-deficient rats was accompanied by a partial restoration of PCA. Restorative effects were also noted with heated and ammonia-treated serum. The return of hemolytic potency and responsiveness to PCA in C'-depleted rats, follow a similar time course. The data presented indicate that the PCA reaction can be studied as a function of at least three variables, antigen, antibody, and a serum constituent resembling C'.

Antibacterial effect of imipenem/relebactam on aerobic Gram-negative bacilli: in vitro simulations of 7 or 14 day human exposures

2019 ◽  
Vol 74 (7) ◽  
pp. 1945-1951 ◽  
Author(s):  
Alan R Noel ◽  
Karen E Bowker ◽  
Marie Attwood ◽  
Alasdair P MacGowan
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Pharmacokinetic Model ◽  
Antibacterial Effect ◽  
Bacterial Load ◽  
Bacterial Burden ◽  
Gram Negative ◽  
Highly Effective ◽  
Emergence Of Resistance

Abstract Objectives We assessed the antibacterial effect of human simulations of dosing with imipenem/relebactam (with or without amikacin) on Enterobacteriaceae or Pseudomonas aeruginosa over 7 or 14 day antibiotic exposures. Methods An in vitro pharmacokinetic model was used to assess changes in bacterial load and population profiles. Results Imipenem/relebactam produced an initial >4 log drop in viable counts followed by suppression for 7 days for Enterobacteriaceae whether the strain was WT, produced KPC enzymes or produced an AmpC enzyme with porin loss. Similarly, with the P. aeruginosa strains, there was an initial >4 log clearance over the first 24 h irrespective of whether the strain was WT, hyperexpressed AmpC or had OprD mutation with porin loss. However, with three of four strains there was modest regrowth over the 7 days. There were no changes in imipenem/relebactam MICs over the 7 days. Addition of amikacin in 7 day simulations resulted in more suppression of pseudomonal growth. In 14 day simulations with P. aeruginosa there was regrowth to 8 log10 by 14 days with imipenem/relebactam alone and associated increases in MICs. Addition of amikacin resulted in clearance from the model and prevented changes in population profiles. Conclusions Imipenem/relebactam was highly effective at reducing the bacterial load of Enterobacteriaceae and there was no emergence of resistance. Against P. aeruginosa, the initial bacterial burden was also rapidly reduced, but there was subsequent regrowth, especially after 7 days of exposure. Addition of amikacin increased the clearance of P. aeruginosa and prevented emergence of resistance.

Activity-dependent changes in extracellular potassium and excitability in turtle olfactory nerve

1987 ◽  
Vol 57 (3) ◽  
pp. 740-754 ◽  
Author(s):  
D. L. Eng ◽  
J. D. Kocsis
Keyword(s):  
Conduction Velocity ◽  
Time Course ◽  
Compound Action Potential ◽  
Olfactory Nerve ◽  
Extracellular Potassium ◽  
Similar Time ◽  
Supernormal Period ◽  
Sucrose Gap ◽  
Activity Dependent

The excitability properties of turtle olfactory nerve (o.n.) were studied in vitro using potassium-sensitive microelectrodes (KSM), a modified sucrose gap chamber, and a standard nerve chamber to measure conduction velocity. A pronounced supernormal period (SNP), as indicated by increased conduction velocity of the o.n. fiber volley, lasting up to several seconds, was observed following a single stimulus. The compound action potential recorded in the sucrose gap chamber showed a prolonged depolarization with a similar time course to the SNP. When stimulation intensity was submaximal the response amplitude, and the extracellular potassium concentration [K+]o, continuously increased during repetitive stimulation. In contrast, when supramaximal stimuli were applied, the amplitude of the o.n. fiber volley was reduced during a high-frequency stimulus train for all responses after the initial one even though latency was maximally reduced, i.e., during supernormal conduction. Superfusion with various levels of K+ elicited changes in the excitability of the o.n. fibers. Small increases in [K+]o above the resting concentration of 2.6 mM led to an increase in resting excitability, whereas larger increases resulted in decreased excitability and conduction block. The SNP was eliminated when extracellular potassium was elevated between 3 and 4 mM above resting levels. Microstimulation of a small bundle of o.n. fibers led to an increase in [K+]o along the bundle but also around adjacent nonactivated fibers. The excitability of these neighboring nonactivated fibers was increased, further indicating the importance of activity-dependent changes in [K+]o in modulating axonal excitability. These results demonstrate the importance of activity-dependent increases in extracellular potassium in modulating nonmyelinated o.n. fiber excitability. They also indicate that increases in [K+]o and an associated membrane depolarization contribute to the increased excitability observed during fiber recruitment and the supernormal period.

scholarly journals Role of nerve growth factor in the development of rat sympathetic neurons in vitro. II. Developmental studies.

1977 ◽  
Vol 75 (3) ◽  
pp. 705-711 ◽  
Author(s):  
L L Chun ◽  
P H Patterson
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Time Course ◽  
Sympathetic Neurons ◽  
Protein A ◽  
Cell Number ◽  
Similar Time ◽  
Nerve Growth ◽  
Virtual Absence

Adrenergic sympathetic neurons were grown for 4 wk in submaximal and saturating concentrations of nerve growth factor (NGF) in the virtual absence of non-neuronal cells. In 0.2 or 5 microgram/ml 7S NGF, the neurons gradually decreased in number during the first week, although fewer neurons died at the higher level. No significant change in cell number was observed thereafter. Total neuronal protein, a measure of cell growth, increased linearly with age in both concentrations of NGF. At each age, neurons in high NGF exhibited greater growth per cell than those in low NGF. The ability of neurons to produce catecholamine (CA) increased dramatically during the second and third weeks in both concentrations of NGF, and along a similar time-course, although neurons in submaximal NGF developed a lesser capacity for CA production. As neurons developed in culture, they became less dependent on NGF for survival and CA production, but even in older cultures, approximately 50% of the neurons died when NGF was withdrawn.

scholarly journals Implication of extracellular zinc exclusion by recombinant human calprotectin (MRP8 and MRP14) from target cells in its apoptosis-inducing activity

2002 ◽  
Vol 11 (3) ◽  
pp. 165-172 ◽  
Author(s):  
Satoru Yui ◽  
Yuichi Nakatani ◽  
Michael J. Hunter ◽  
Walter J. Chazin ◽  
Masatoshi Yamazaki
Keyword(s):  
Calcium Binding ◽  
Time Course ◽  
Specific Activity ◽  
Physical Contact ◽  
Target Cells ◽  
Dialysis Membrane ◽  
Similar Time ◽  
Zinc Chelator ◽  
The Individual

Background: Calprotectin is a calcium-binding and zinc-binding protein complex that is abundant in the cytosol of neutrophils. This factor is composed of 8 and 14 kDa subunits, which have also been termed migration inhibitory factor-related proteins MRP8 and MRP14. We previously reported that rat calprotectin purified from inflammatory neutrophils induces apoptosis of various tumor cells or normal fibroblasts in a zinc-reversible manner.Aim: The present study was undertaken to elucidate which subunit is responsible for the apoptosis-inducing activity, and to explore the mechanism of zinc-reversible apoptosis induction.Methods: The apoptosis-inducing activity of recombinant human MRP8 (rhMRP8) and recombinant human MRP14 (rhMRP14) was examined against EL-4 lymphoma cellsin vitro. To determine whether zinc deprivation by calprotectin was essential for the cytotoxicity, the activity of calprotectin was tested under conditions where physical contact between the factor and the cells was precluded by a low molecular weight cut-off dialysis membrane.Results: The cytotoxicity of rhMRP14 against EL-4 cells was first detected at 10 μM in a standard medium, whereas rhMRP8 caused only marginal cytotoxicity at 40 μM. A mixture of both proteins showed higher specific activity (onset of cytotoxicity at 5 μM). When the cells were cultured in divalent cation-depleted medium, each dose-response curve was shifted to about a four-fold lower concentration range. Calprotectin was found to induce cell death even when the complex and the target cells were separated by dialysis membrane. A membrane-impermeable zinc chelator, diethylenetriamine pentaacetic acid (DTPA), also induced target cell apoptosis in a similar time-course as calprotectin. Moreover, the activities of calprotectin and DTPA were completely inhibited by the presence of zinc ions.Conclusion: These data indicate that calprotectin has higher specific activity to induce apoptosis than the individual subunits, and that the mechanism is exclusion of zinc from target cells.

DER TSH-RESERVE-TEST AN DER RATTE

1963 ◽  
Vol 44 (4) ◽  
pp. 570-580 ◽  
Author(s):  
H. W. Iff ◽  
H. Studer ◽  
F. Wyss
Keyword(s):  
Time Course ◽  
Term Treatment ◽  
Short Term ◽  
Iodide Uptake ◽  
Short Term Treatment ◽  
Similar Time ◽  
Clinical Method ◽  
Tsh Secretion

ABSTRACT A rebound of 131I-uptake by the thyroid gland after a thyrostatic treatment may be taken as evidence of an unimpaired pituitary TSH-secretion. The iodide uptake in vivo and the iodide accumulation in vitro were studied in rat thyroids following a short-term treatment of the animals with carbimazole. The experiments served as models for the clinical method of assaying the pituitary TSH-reserve. The total iodide uptake reaches a peak 36 hours after the end of a carbimazole treatment and returns to normal after 96 hours. The rebound of the iodide accumulation has a similar time course. Extending the carbimazole treatment from 6 to 12 days leads to a definite increase in the peak iodide accumulation while the peak of the total iodide uptake was not significantly increased. The duration of the rebound-phase is not changed by prolonged carbimazole treatment.

Sign in / Sign up

Export Citation Format

Share Document