Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein degradation in skeletal muscle increases with fever and sepsis. Our studies indicate that prostaglandin E2 (PGE2) is an important regulator of muscle proteolysis that seems to signal this increase in fever. When rat skeletal or cardiac muscles were incubated with arachidonate, rates of protein breakdown rose and protein balance became more negative. Aspirin or indomethacin, which prevented synthesis of PGE2, markedly reduced this effect. By itself PGE2 stimulated proteolysis without altering protein synthesis. PGE2 seems to increase proteolysis in the lysosomes, inasmuch as leupeptin and Ep-475 inhibit this response. These inhibitors inactivate lysosomal thiol proteases in the muscles without affecting the Ca2+-activated protease. (In fact, complete inactivation of the latter enzyme with mersalyl did not reduce overall proteolysis in the muscles). When muscles from feverish rats were incubated in vitro, they showed greater protein breakdown and PGE2 synthesis than muscles from normal animals. Addition of indomethacin eliminated this difference. Leukocytic pyrogen (interleukin 1), a protein released by monocytes that signals the onset of fever, also seems to signal increased muscle PGE2 synthesis and muscle proteolysis. This protein enhanced both processes dramatically in the isolated muscles. These findings suggest that cyclooxygenase inhibitors may be useful in the treatment of patients showing excessive protein breakdown.
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PMID:Control of protein degradation in muscle by prostaglandins, Ca2+, and leukocytic pyrogen (interleukin 1). 632 20

Amphotericin B, a systemic antifungal agent, has not been associated with clinical evidence of cardiac toxicity. We report the case of a 76-year-old patient who developed transient asystole with cardiovascular collapse on two occasions, which coincided with infusion of amphotericin B. The patient was semicomatose and had candida septicemia and renal failure. Serum potassium and digoxin levels were elevated, and serum calcium was low when these episodes occurred. Subsequent postmortem examination revealed no gross evidence of cardiac disease apart from fungal vegetations on the aortic valve. A clear causal relationship between amphotericin B and transient asystole is not demonstrated, but a temporal association, confirmed with rechallenge, is documented in this patient. No similar cases were found in a review of the literature.
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PMID:Transient asystole associated with amphotericin B infusion. 634 98

The abilities of Yersinia pestis to undergo restriction in Ca2+-deficient medium with concomitant production of V and W antigens (Vwa+) and to absorb exogenous pigments (Pgm+) are established virulence factors. Mutation of Y. pestis to Pgm- is known to promote resistance to pesticin (Pstr) and reduced lethality by peripheral routes of injection. Vwa+ Pgm- isolates of Y. pestis were shown in this study to retain virulence in mice when injected intravenously. Although Pgm- in appearance, wild-type cells of Yersinia pseudotuberculosis and Yersinia enterocolitica may also be sensitive to pesticin. Pstr mutants of Vwa+ strains of these species were similarly of reduced virulence, especially by peripheral routes of injection. The consequences of mutation to Vwa- and Pgm- or Pstr on growth and persistence in vivo were determined. After intravenous injection, Vwa+ yersiniae of all species exhibited sustained growth in mouse spleen, liver, and lung and accumulated in blood. Septicemia was not observed after similar injection of Vwa- mutants which were unable to maintain comparable rates of net increase in tissues. Mutation to Pgm- or Pstr did not influence proliferation but resulted in enhanced clearance from organs. It is known that reticuloendothelial cells serve as favored sites of replication for all wild-type yersiniae. Our results are consistent with the hypothesis that the Vwa+ phenotype favors growth within macrophages and that the Pgm+ and pesticin-sensitive phenotypes permit long-term, probably extracellular, retention within organs. Virulence in standard animal models (mice, rats, and guinea pigs) was not correlated with resistance to the bactericidal action of serum.
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PMID:In vivo comparison of avirulent Vwa- and Pgm- or Pstr phenotypes of yersiniae. 636 86

Previous studies from this laboratory described myocardial depression in an arterially perfused rabbit interventricular septum following perfusion with acute septic plasma. Calcium is critical for maintenance of cardiac contractility on a beat-to-beat basis. We have investigated calcium flux in the septal tissue to determine whether altered calcium flux explains the impaired cardiac function during sepsis. Twenty-two rabbit septa were perfused with control and septic perfusate (cryo-precipitated plasma + RBCs) and calcium flux determined in seven experiments. Perfusate cations (Ca++, Na+, K+, and H+) were measured, tissue function and arterial pressure were monitored. Developed tension decreased 46%, acceleration of tension change fell 42%, and arterial pressure decreased 26%, all highly significant. All septa recovered after return to control perfusate. The septic perfusate Ca++ was significantly lower than control perfusate, while K+ and H+ were significantly elevated. Ion flux studies, however, could not demonstrate altered calcium flux associated with the depressed contractility.
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PMID:Myocardial depression. The effect of Ca++ and calcium flux during sepsis. 637 32

Untreated septic shock results in depletion of extracellular fluid, cellular swelling, increased intracellular sodium, and decreased intracellular potassium concentrations in primate skeletal muscle. The Langer rabbit heart interventricular septal preparation was used to determine whether similar changes occur in cardiac muscle during sepsis. Rabbit septa (n = 17) were perfused with control and septic rabbit plasma plus red blood cells. Tissue contractility (developed tension [DT] and rate of tension change [dP/dt]) was followed, plasma cations were measured (Na+, K+, Ca2+, H+), perfusion pressure (PP) was monitored, and 42K efflux was determined. The effect on 42K efflux caused by the addition of potassium chloride to control plasma was determined. During perfusion with septic plasma there was significant decline of septal function (P less than 0.001). In 12/17 experiments DT fell 77.8 +/- 21.4% and dP/dt fell 75.8 +/- 24.8% from control values (means +/- 1 SD). All septa recovered when perfusion with control plasma was resumed. If [K+] was increased in control plasma during 42K washout, the percentage increase of effluent counts per minute per minute correlated with the percentage rise of control plasma [K+] (r = 0.95, P less than 0.001). During perfusion with septic plasma there was no similar correlation (r = 0.277). 42K efflux increased during septic plasma perfusion independent of the differences between control and septic plasma [K+], demonstrating abnormal myocardial K+ efflux. An abnormal efflux of K+ is seen during septic plasma perfusion similar to that described in primate skeletal muscle. It is associated with and may be a mechanism of action for the observed fall of contractility.
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PMID:Altered potassium flux and myocardial dysfunction during sepsis. 638 64

The caprine variant of Mycoplasma mycoides subsp mycoides causes septicemia with coagulopathy in goats. Pathogenetic mechanisms that might explain the coagulopathy, the ability of the Mycoplasma to persist in the blood, and its specificity for goats were studied. Severe endothelial damage was seen by electron microscopy of goat aorta tissue exposed in vitro to 10(7) colony-forming units of mycoplasmas. The Mycoplasma did not damage 51Cr-labeled adherent cells from peripheral blood of goats. The hemolytic complement titer was reduced by 94%, 50%, 50%, and 25% in guinea pig, calf, sheep, and goat serum, respectively, 30 minutes after treatment with 8 X 10(9) colony-forming units of the Mycoplasma. Freshly prepared serum from these animal species killed the Mycoplasma. Heat-inactivated serum was not mycoplasmacidal. Complement from these 4 animal species was activated by the Mycoplasma through the classical pathway, because ethyleneglycoltetraacetic acid precipitation of serum Ca2+ inhibited activation. Proof that the classical pathway was functional in goats was not conclusive because Ca2+ supplementation of ethyleneglycoltetraacetic acid-treated serum did not restore complement activity. Endothelial damage and complement activation may explain the coagulopathy. The function that complement activation may have in the inflammatory response of this disease is not known. Difference in susceptibility of calves, sheep, and goats to M mycoides septicemia cannot be explained by species variation in complement mycoplasmacidal activity.
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PMID:Effect of the caprine variant of Mycoplasma mycoides subsp mycoides on endothelium, monocytes, and complement of guinea pig, calf, sheep, and goat serum. 639 28

Cell lines Lu-65 and SK-Luci-6 were established from two patients with anaplastic (non-oat cell) lung cancers. These cell lines showed in vivo and in vitro functional activities that could explain the paraneoplastic syndromes which were clinically manifested. In both patients, elevated white blood cell counts occurred in the absence of any evidence of sepsis. Tumor fragments taken directly from one patient and transplanted to nude mice produced a progressive leukocytosis in the mice. Tissue culture-derived cells from both cell lines enhanced white blood cell numbers following heterotransplantation to nude mice. Cell-free extracts from both cell lines were found to enhance granulocyte-macrophage colony formation in soft agar. Greater colony formation was consistently found with the cell line (SK-Luci-6) that was derived from the patient manifesting the more marked leukocytosis. These data suggest that the tumor cells release colony-stimulating activities. Coincidently, one cell line (Lu-65) synthesized and released large amounts of prostaglandin E2 with little or no other prostaglandin product; the other cell line produced no prostaglandins. When the tumor cell lines were cocultured with explanted fetal rat bones, enhanced bone resorption with excessive calcium release occurred. Bone-resorbing activity correlated with tumor prostaglandin synthesis for the cell line releasing prostaglandin E2. An osteolytic factor that was neither prostaglandin nor parathyroid hormone was released by the SK-Luci-6 cell line. Hypercalcemia was a persistent feature only in the patient from whom the latter tumor line was derived.
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PMID:In vivo and in vitro biological activities of two human cell lines derived from anaplastic lung cancers. 640 6

Moderate hypercalcaemia occurred in a 17-year-old male who was immobilized with abdominal and right hip sepsis for 9 months after a motor vehicle accident. The hypercalcaemia was due to bone resorption, with a urine hydroxyproline:creatinine ratio of 0.203 (normal less than 0.017) and a urine calcium loss of 22.9 mmol/24 hr, associated with impaired renal function. There was radiological evidence of severe bone demineralization in the pelvis over 42 weeks. Radiocalcium absorption, using 47Ca, was decreased (0.17, normal range 0.35-1.30), renal tubular maximum for calcium reabsorption was decreased (1.61 mmol/1 glomerular filtrate, normal range 1.8-2.2), the serum parathyroid hormone concentration was in the low normal range (3.2, 3.6 u/l, normal range 2-6) and the plasma 1,25-dihydroxy-vitamin D concentration was decreased despite a normal 25-hydroxy-vitamin D concentration, indicating suppression of the parathyroid, 1,25-dihydroxy-vitamin D axis. The patient was found to be hypogonadal at 41 weeks after admission and testosterone therapy was begun, with associated improvement in mobilization and a reduction of the hypercalcaemia.
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PMID:Immobilization hypercalcaemia with severe bone mineral loss and hypogonadism. 646 82

Parathyroid carcinoma is a rare cause of hyperparathyroidism. Cure results from successful en bloc resection. However, because of its rarity, the malignant nature may not be appreciated at the initial operative procedure and as a result, definitive resection may not be accomplished. However, even with extensive en bloc resections, local recurrences do occur and patients die of metabolic derangements associated with hypercalcemia. Thus in addition to operative intervention, palliative chemotherapy may be required to control the hypercalcemia. Radiotherapy has been unsuccessful. A single case of nonfunctioning parathyroid carcinoma responding to treatment with methotrexate, Adriamycin, cyclophosphamide, and CCNU has been reported. We report a case of recurrent functioning parathyroid carcinoma treated with dacarbazine (DTIC) in which biochemical and pathologic evidence of at least a partial response was seen. The patient, a 33-year-old woman, had undergone five previous neck explorations during a 26-month period for aggressive locally recurrent disease. Before DTIC therapy the intact parathyroid hormone (PTH) level was 1032 pg Eq/ml (normal 163 to 347 pg Eq/ml) and the serum calcium level was 16.8 mg/dl (normal 8.8 to 10.0 mg/dl). After a course of DTIC there was a marked improvement in her clinical status and biochemical parameters (intact PTH 545 pg Eq/ml; serum calcium 11.8 mg/dl). For 2 months her condition stabilized, with PTH levels between 700 and 760 pg Eq/ml and serum calcium levels between 10.2 and 16.0 mg/dl. With a slowly progressive rise in biochemical parameters a second course of DTIC was initiated and a marked drop in serum calcium levels (5.7 mg/dl) occurred, but PTH levels remained unchanged. A progressive course of septicemia, malnutrition, and disseminated intravascular clotting ultimately lead to her death 4 weeks later. At autopsy examination the tumor was confined to the neck. Grossly and microscopically there was extensive central as well as peripheral necrosis of the tumor, which was thought to be the result of the cytotoxic effect of DTIC. From this experience and because of the grim prognosis in patients with recurring parathyroid carcinoma, it may be that aggressive use of chemotherapy with DTIC early in the course of treatment should be considered.
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PMID:Parathyroid carcinoma: biochemical and pathologic response to DTIC. 650 66

Studies utilizing animal models of circulatory shock have revealed mitochondrial structural and functional damage in the liver, kidney, and brain. Adenosine triphosphate (ATP) synthesis and calcium transport rates of these mitochondria decline significantly during circulatory shock. The specific enzyme functions affected deleteriously by low flow states are the ATP synthetase, adenine nucleotide translocase, and carrier-mediated calcium transport. Other cellular alterations that possibly are responsible for, or are related to, the shock-induced mitochondrial deterioration are discussed. Differences in the mitochondrial responses to endotoxemia and hyperdynamic sepsis are described. Data are presented on the beneficial effects of early glucocorticoid treatment in prevention of mitochondrial functional deterioration during endotoxemia.
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PMID:Mitochondrial function in shock. 651 84


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