Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sepsis has been shown to impair ventilatory muscle function. To determine whether this can be attributed to direct effects of inflammatory mediators on muscle fibers, we carried out in vitro studies on hamster costal diaphragm. Baseline measurements included supramaximal peak twitch (Pt) and tetanic tension (Po), twitch half relaxation time (1/2RT) and time-to-peak tension (TTP), and force frequency response (15 to 80 Hz). Fatigability was evaluated using 60-Hz stimulations at a duty cycle of 0.4 until tension fell to 50% of baseline. Preparations were then incubated in one of the following for 60 min: (1) Krebs solution (n = 5), (2) nonstimulated monocyte supernatant (n = 5), or (3) lipopolysaccharide-stimulated monocyte supernatant (n = 5). Baseline Pt, Po, 1/2RT, TTP, force frequency response, and fatigue profile were similar between groups. After incubation there was a significant fall in Pt (mean +/- SD, 538 +/- 65 to 288 +/- 13 g/cm2, p < 0.05) and Po (1,268 +/- 132 to 921 +/- 64 g/cm2, p < 0.05) in the LPS group, with no change in the other groups. There was no change in TTP; however, 1/2RT was lower in the LPS-stimulated group after incubation (p < 0.05). There was a rightward shift in the force frequency response for the LPS-stimulated group (p < 0.05). When normalizing for initial Po, there was no significant change in the time to fatigue for any of the three groups. This study demonstrated that monocyte secretory products impair diaphragmatic contractility in vitro by a direct effect on muscle fibers.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Monocyte inflammatory mediators impair in vitro hamster diaphragm contractility. 148 41

There is a strong association between PSC and IBD. PSC is the most common hepatobiliary lesion seen in association with IBD. Whether there are two subsets of PSC, one associated with IBD and one unassociated, is controversial. A lower male to female ratio in patients without IBD supports this view. The demonstration of the haplotype DRw52a in 100% of patients with PSC, irrespective of the absence of IBD, speaks against this view. Patients with isolated PSC tend to present with jaundice, pruritus, and fatigue more frequently than those with combined PSC and IBD. There may also be a difference in bile duct involvement between patients with and without IBD combined with PSC. Apart from usually being a total colitis, either Crohn's colitis or UC, the IBD associated with PSC cannot be distinguished from IBD without PSC with respect to symptoms and clinical course. Patients with combined IBD and PSC may have somewhat worse prognosis than those with isolated PSC. The majority of patients developing BDC have concomitant IBD, suggesting that patients without IBD represent a different subgroup of PSC and run a different clinical course. Most studies have, however, found no differences in epidemiology, pathogenetic factors, clinical findings related to the hepatobiliary disease and prognosis between those who present with PSC alone and those who present with combined PSC and IBD. A major problem when discussing the relationship between IBD and PSC is that the bowel is inadequately examined in many of the studies relating to this question.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship of inflammatory bowel disease and primary sclerosing cholangitis. 204 87

A rat model was used to study the effects of endotoxemic shock in vivo on diaphragmatic tension generation and diaphragmatic metabolism in vitro. Animals were injected with E. coli lipopolysaccharide (30 mg/kg) and killed at fixed times after injection. The hemidiaphragms were isolated in an organ bath, and tension generation was measured during electrical stimulation of the phrenic nerve or diaphragmatic muscle. Diaphragmatic oxygen consumption was measured in vitro during rest and during in vivo stimulation. Adenosine triphosphate and glycogen concentrations were measured in vivo before the animals were killed and in vitro. Tension generation was reduced in a time-dependent fashion after endotoxin at all stimulation frequencies. Both contractile fatigue and transmission fatigue were present. Glycogen stores were reduced but not depleted. ATP concentration was reduced in vivo but recovered in vitro. Diaphragmatic oxygen consumption was reduced in vitro at rest and during stimulation. The results suggest that endotoxemic shock results in diaphragmatic fatigue in a time-dependent fashion, that impaired neural or neuromuscular transmission is present in vitro, and that impaired oxygen consumption in the shocked diaphragm is associated with reduced high-energy-phosphate stores.
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PMID:Diaphragmatic fatigue after endotoxemic shock in rats: in vitro function and metabolism. 221 69

The activity of 38 calves aged 15-30 days of the Simenthal breed and of crosses with Ireshire was studied before and after transportaton at a distance of 38-100 km. It was established that transportation causes fatigue, thirst and a weight reduction of 4.3 kg, due to loss of liquid in the calf's organism. Caughing, soft faeces, even diarrhea, 1.5 degrees C higher rectal temperature, and 3.0 degrees C lower skin temperature, were recorded. the MacClure--Oldridge test proved twice as fast. As a result of hemoconcentration hemoglobin and hematocrite were higher. Eosinopaenia and neutrophylia with a nuclear deviation to the left similar to the reaction of experimentally induced lipopolysaccharide fever were established. On the 72d hour lymphocytosis and an enhanced lymhocytal index were observed. Transportation led to 15-18% higher number of phagocyted neutrophyls, 30-35% higher Wright number and nearly two times higher total blood phagocytal ability. Seventy two hours after two times higher total blood phagocytal ability. Seventy two hours after transportation the total blood phagocytal ability was reduced 15%. Another effect of calf transportation was the reduced total immunological reactivity, scored by the skin test of Yoffe.
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PMID:[Reactivity changes in calves during transportation]. 741 35

Despite considerable progress in our understanding of the phenomenology of sleep and wakefulness, their regulation and peculiar functions are poorly understood. Recent animal research has revealed considerable evidence for interactions between host defense and sleep. Therefore, it has been hypothesized that host response mediators, mainly cytokines like interleukin-1 (IL-1), are involved in physiological sleep regulation. Furthermore, it has been suggested that sleep, and non rapid eye movement (NREM) sleep in particular, has an immuno-supportive function. In humans, sleep-host defense interactions are just starting to be understood. There is quite good evidence that some viral diseases cause excessive sleepiness. Other infectious diseases induce, however, serious disturbances of the distribution of sleep and wakefulness rather than excessive sleep. In addition, some disorders with excessive sleep, daytime fatigue or disturbed night sleep as prominent symptoms are thought to involve, at least in part, immuno-pathophysiological mechanisms. Experimental settings have only recently been used to elucidate host defense-sleep interactions in humans. The effects of endotoxin, a cell-wall lipopolysaccharide of gram-negative bacteria, on sleep have been tested in different settings in healthy volunteers. Endotoxin transiently suppresses rapid eye movement (REM) sleep independently of the time of the day of administration. Only low doses, given in the evening, promote NREM sleep. Electorencephalogram (EEG) power in higher frequency bands is enhanced during NREM sleep, whereas delta activity is not affected. In rats and rabbits, on the other hand, the effects of endotoxin and of the mediators of its activity on REM sleep are variable. Enhanced NREM sleep is a common finding and most pronounced during the active part of the nycthemeron and, in general, EEG delta activity is augmented. In view of these species differences, hypotheses regarding the underlying mechanisms and the biological significance of host defense-sleep interactions, primarily derived from the results of animal studies, may not entirely fit human physiology. They should therefore be re-evaluated and probably modified, through the use of additional experimental approaches in humans.
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PMID:Influence of host defense activation on sleep in humans. 749 10

Natural killer (NK) cells may be expanded in vivo with a prolonged course of daily subcutaneous interleukin-2 (IL-2). However, cellular activation requires higher concentrations of IL-2 than are achieved with low-dose therapy. The objective of the current trial was to determine the toxicity and immunological effects of periodic subcutaneous intermediate-dose IL-2 pulses in patients receiving daily low-dose therapy. A group of 19 patients were treated with daily subcutaneous low-dose IL-2 at 1.25 x 10(6) International Units (1.25 MIU) m(-2) day(-1). After 4-6 weeks, patients received escalating 3-day intermediate-dose IL-2 pulses administered as single daily subcutaneous injections, repeated at 2-week intervals. The maximum tolerated pulse dose was 15 MIU m(-2) day(-1), with transient hypotension, fatigue, and nausea/vomiting dose-limiting. Subcutaneous IL-2 resulted in in vivo expansion of CD56+ NK cells (796+/-210%) and CD56bright natural killer (NK) cells (3247+/-1382%). Expanded NK cells coexpressed CD16, and showed lymphokine-activated killer activity and antibody-dependent cellular cytotoxicity in vitro. Intermediate-dose pulsing resulted in serum IL-2 concentrations above 100 pM. Cellular activation was suggested by rapid margination of NK cells following pulsing, coincident with peak IL-2 levels, with return to baseline by 24 h. In.addition, interferon gamma production in response to lipopolysaccharide was augmented. Subcutaneous daily low-dose IL-2 with intermediate-dose pulsing is a well-tolerated outpatient regimen that results in in vivo expansion and potential activation of NK cells, with possible application in the treatment of malignancy and immunodeficiency.
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PMID:Evaluation of natural killer cell expansion and activation in vivo with daily subcutaneous low-dose interleukin-2 plus periodic intermediate-dose pulsing. 975 16

In an investigator-blinded study, adherent (monocytes) and non-adherent cells (lymphocytes) from patients with chronic fatigue syndrome (CFS) were examined on two separate occasions (when feeling 'fatigued' and when feeling 'rested') for in vitro spontaneous, phytohemagglutinin- (PHA, for lymphocytes), and lipopolysaccharide- (LPS, for monocytes) induced production of IL-6 by ELISA assay. A group of CFS patients and controls were also subjected to exercise-induced fatigue ('experimental fatigue') and IL-6 production was compared, in a double-blinded manner, prior to and following induction of fatigue. A significant increase in spontaneous, PHA- and LPS-induced IL-6 secretion by both lymphocytes and monocytes was observed in CFS patients during 'natural fatigue' as compared to during state. However, no such changes in IL-6 production were observed during 'experimental fatigue'. These data suggest a role of IL-6 in natural symptomatology and perhaps in the pathogenesis of CFS. In addition, the data demonstrate that laboratory-induced fatigue (experimental fatigue) may not be a good model to study immunological changes in CFS; immunological parameters should be studied in a longitudinal manner during the natural course of the disease.
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PMID:Increased production of interleukin-6 by adherent and non-adherent mononuclear cells during 'natural fatigue' but not following 'experimental fatigue' in patients with chronic fatigue syndrome. 991 31

The aim of the present study was to compare the effects of exercise at 80% VO2max (resulting in fatigue within 1 h) with more prolonged exercise at a lower work rate (55% VO2max for up to 3 h) on blood neutrophil function and plasma concentrations of cortisol, glutamine and glucose. Eighteen healthy male subjects (mean+/-SD age 22.5+/-3.7 yrs, VO2max 60.1+/-6.6 ml x kg(-1) x min(-1)) cycled on an electrically braked ergometer at 80% VO2max to fatigue (37+/-19 min). On another occasion, separated by at least one week, subjects performed exercise on the same ergometer at 55% VO2max for 3 h or to fatigue, whichever was the sooner. Mean exercise time was 164+/-23 min. The order of the trials was randomised. Both exercise bouts caused significant (p<0.05) elevations of the blood leucocyte count and plasma cortisol concentration and reductions in the in vitro neutrophil degranulation response to bacterial lipopolysaccharide and oxidative burst activity. After exercise at the lower work rate for a longer duration, plasma cortisol concentration was higher, blood leucocyte and neutrophil counts were higher, blood lymphocytes, plasma glucose and indices of neutrophil function were lower than those observed at 80% VO2max. Plasma glutamine only fell significantly during recovery after the more prolonged exercise. We conclude that when exercise is very prolonged, the diminution of innate immune function is greater, or at least as great as that observed after fatiguing exercise at higher work rates. Furthermore, reductions in neutrophil function after exercise at 80% VO2max were not related to changes in the plasma glutamine concentration, although both plasma glutamine and neutrophil function were decreased at 1 and 2.5 h post-exercise in the long duration exercise trial.
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PMID:Effects of exercise intensity, duration and recovery on in vitro neutrophil function in male athletes. 1019 Jul 75

Carbohydrate (CHO) beverage ingestion appears to influence neutrophil functional responses to prolonged exercise of a fixed duration. The aim of this randomised study was to examine the effect of CHO (5% w/v) beverage ingestion on lipopolysaccharide (LPS)-stimulated neutrophil degranulation responses in nine recreationally active males who cycled at 75% VO2 max until fatigue. On two separate occasions, subjects ingested either placebo (PLA) or CHO beverages before and at 15 min intervals during the exercise. Subjects exercised for 31% longer on the CHO trial compared with the PLA trial (P < 0.05). At fatigue plasma glucose concentration was significantly lower on the PLA trial compared with the CHO trial (P < 0.05). Plasma cortisol concentrations had increased similarly on both trials at this time. A marked neutrophilia was evident at fatigue and throughout the 4 h recovery period, the magnitude of which was similar on both trials. At fatigue LPS-stimulated elastase release per neutrophil had fallen similarly on both trials compared with pre-exercise values (47% and 50% on the PLA and CHO trials, respectively). In conclusion, our results suggest that CHO beverage ingestion has negligible influence on the hormonal, circulating neutrophil and LPS-stimulated neutrophil degranulation responses when exercise is performed to fatigue.
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PMID:Carbohydrate beverage ingestion and neutrophil degranulation responses following cycling to fatigue at 75% VO2 max. 1135 27

Bojungikki-tang (BIT) has been widely used to treat patients suffering from chronic fatigue syndrome (CFS). However, its effect has not been yet investigated experimentally. Based upon the clinical presentation of CFS, we hypothesized that cytokines may play a role in the pathogenesis of the disease. We studied the effect of BIT on lipopolysaccharide (LPS)-induced various cytokines production in peripheral blood mononuclear cells (PBMC) of CFS patients. Bojungikki-tang (1 mg/mL) significantly inhibited LPS-induced tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta1 production by 63.55% +/- 0.19%, 55.06% +/- 0.27%, 48.23% +/- 0.48%, 54.09% +/- 0.76%, respectively (P < 0.05). Bojungikki-tang showed a slightly lower inhibitory effect of LPS-induced Interferon (IFN)-gamma production. These results suggest that BIT may be useful in treating fatigue associated with chronic diseases.
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PMID:Effect of bojungikki-tang on lipopolysaccharide-induced cytokine production from peripheral blood mononuclear cells of chronic fatigue syndrome patients. 1468 92


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