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At least 217 records · Page 12Linked to original sources
PubMed1980

Synthesis and pyrogenic effect of 3 alpha, 7 alpha-dihydroxy-5 beta-androstan-17-one and 3 alpha-hydroxy-5 beta-androstane-7, 17-dione.

The first chemical synthesis of 3 alpha, 7 alpha-dihydroxy-5 beta-androstan-17-one and 3 alpha-hydroxy-5 beta-androstane-7, 17-dione is reported. In this method, the 17 beta-side chain of commercial chenodesoxycholic acid was degraded in 6 steps after selective protection of the hydroxyl groups: 3 alpha-OH by a tert-butyldimethylsilyl group and 7 alpha-OH by an acetoxy group. The capacity of 3 alpha, 7 alpha-dihydroxy-5 beta-androstan-17-one and 3 alpha-hydroxy-5 beta-androstane-7, 17-dione to release a pyrogen by human leukocytes was investigated by two independent methods: supernatants from leukocytes incubated with a steroid are injected to rabbits whose fever is measured, or tested by the Limulus Test (a pyrogen detection technique). The 7-keto substituted etiocholanolone still possessed pyrogenic activity, while the 7 alpha-hydroxyl substituted one did not.

Animals↗
PubMed1991

A novel process for preparing an acellular pertussis vaccine composed of non-pyrogenic toxoids of pertussis toxin and filamentous hemagglutinin.

A novel process for preparing non-pyrogenic toxoids of pertussis toxin (PT) and filamentous hemagglutinin (FHA) is described. The process consists of chromatographies on perlite then on hydroxylapatite. Purification yields for PT and FHA are 62 and 68%, respectively. The purification process takes advantage of the novel use of perlite (a filter aid) for the simultaneous purification of PT and FHA. The hydroxylapatite, in addition to removing the remaining contaminants, also concentrates the antigens. The resulting PT and FHA are approximately 95% pure, and are non-pyrogenic as judged by the rabbit pyrogen test. The purification process is simple, inexpensive, and does not use blood components or toxic substances. The mild conditions in which the PT and FHA are purified ensure the recovery of native protein. The purified PT and FHA are detoxified in the presence of glycerol using glutaraldehyde and formaldehyde, respectively, to produce antigenic components of an acellular pertussis vaccine. The final PT and FHA toxoids are immunogenic in guinea-pigs and have been shown to be protective in the mouse intracerebral challenge test.

Bordetella pertussis↗
PubMed1984

Activation of acute-phase responses by intrapreoptic injections of endogenous pyrogen in guinea pigs.

The acute-phase reaction (APR) is the concatenation of events that develops in response to infectious or other acute inflammatory stimuli. It includes fever and changes in plasma trace metal and glycoprotein levels. Endogenous pyrogen (EP) is believed to be the mediator of the APR. It acts within the preoptic-anterior hypothalamus (PO) to initiate fever; prostaglandins E (PGE) may modulate this action. To determine whether the nonfebrile responses to EP also are mediated by the PO and through PGE, guinea pigs were injected bilaterally intra-PO (iPO) with homologous EP (1 microliter) or PGE2 (0.1 microgram), and their colonic temperatures (Tco) and plasma iron (Fe), zinc (Zn), copper (Cu), and N-acetylneuraminic acid (NANA) levels were measured. For comparison, EP (2 ml) also was injected intraperitoneally (IP). Heat-denatured EP (delta EP) or pyrogen-free saline (PFS) was the corresponding control. Fevers were induced by IP EP (1.0 +/- 0.1 degrees C [mean +/- SD]), iPO EP (1.1 +/- 0.2 degrees C), and iPO PGE2 (1.4 +/- 0.2 degrees C); neither delta EP nor PFS was pyrogenic. Plasma Fe and Zn levels were decreased significantly after IP EP, but unchanged after iPO EP and PGE2. Plasma Cu and NANA levels were elevated significantly following both IP and iPO EP, but not after iPO PGE2. delta EP or PFS did not cause any changes, by either route. It appears, therefore, that EP-induced fever and rises in plasma Cu and NANA are mediated by the PO, while the decreases of plasma Fe and Zn are direct, peripheral effects. On the other hand, PGE2 appears to be involved only in the central febrile response. Indeed, guinea pigs, pretreated with indomethacin (5 mg/kg, IP), and injected iPO with EP or IP with S. enteritidis endotoxin (2 micrograms/kg), did not develop fever, but exhibited the rise in plasma Cu and NANA.

Animals↗
PubMed1987

Differential production of endogenous pyrogen by human peripheral blood leucocytes following interaction with H3N2 or H1N1 influenza viruses of differing virulence.

Fever and other constitutional effects of influenza (headache, myalgia, listlessness, nausea, shivering, anorexia and depression) result from liberation of endogenous pyrogen (EP) from phagocytes. These effects are milder for recent H1N1 influenza virus isolates than for H3N2 strains. Interaction with human peripheral blood leucocytes in vitro showed that H1N1 strains, A/USSR/90/77 and A/Fiji/15899/83, elicited significantly less EP (as assessed by the rabbit pyrogen assay) than two virulent clones, 7a and 64c, of the A/Puerto Rico/8/34-A/England/939/69 (H3N2) reassortant virus system. Similar observations were made with UV-inactivated A/Fiji/15899/69 and clone 64c. These results are in accord with the differential severity of fever produced by these strains in ferrets when intranasally infected or intracardially inoculated with live and inactivated viruses. They show that influenza virus strains differ in capacity to induce EP from phagocytes. Furthermore, the observations with inactivated virus show that certain virion components are pyrogenic and differ in quantity or nature between strains. These results are important in relation to the differential severity of influenza epidemics and the reactogenicity of vaccine strains.

Animals↗
PubMed1985

[Limulus test using a chromogenic method: application to the control of pyrogens in blood derivatives].

We report here the application of the LAL Test to a chromogenic substrate to detect endotoxins in Human Blood Products. In order to reduce the cost, we used a microplate procedure with the Multiskan Reader. Quantitative results in the range of 0,01 to 0,1 ng/ml allowed for a good correlation with the Rabbit Pyrogen test. For 20% albumins and 4% albumins, the mean endotoxins levels of non pyrogenic lots were 0,38 +/- 0,18 and 0,09 +/- 0,03 ng/ml. All the lots which passed the Rabbit Pyrogen test had endotoxins levels lower than 1 ng/ml and 0,2 ng/ml, respectively. We can use this test for other plasma derivatives; Gammaglobulines and PPSB are easily tested. Dried Concentrated Antihemophilic Factor and Dried plasma contain citrate which inhibits the reaction. Dilution and Addition of Calcium Chloride overcome this inhibition. For dried plasma, we should destroy plasma inhibitors by heating at 75 degrees C. This sensitive and reproductible in vitro assay improves the control of pyrogenecity in Human Blood Products.

Blood Transfusion↗
PubMed1981

Measurement of hypozincaemia in mice: a sensitive test for detection of pyrogens.

1. The effect of bacterial pyrogens on plasma zinc concentration in mice was studied as a method of bioassay for these substances. 2. A dose-related depression of plasma zinc concentrations was observed 4 h after intravenous injection of doses of 0.05-500 ng of purified endotoxins of Salmonella abortus equi, Shigella dysenteriae and Escherichia coli. Responses were dose-dependent and reproducible for each endotoxin in five strains of mice. 3. Tolerance to endotoxin could be induced in mice by injection of doses of 500 ng but was not seen with doses of less than 5 ng, even after repeated treatment. 4. Dinitrophenol, a metabolic inhibitor, and amphetamine, a metabolic enhancer, did not affect plasma zinc levels, indicating that changes in basal metabolic rate do not affect the outcome of this assay. The effects of pyrogenic materials other than endotoxin on plasma zinc levels were also tested and the results suggest that measurement of hypozincaemia in mice provides the basis for a simple, practical and inexpensive test for endotoxins and other pyrogens.

Amphetamine↗
PubMed1966

Studies on the pathogenesis of fever. XIV. Further observations on the chemistry of leukocytic pyrogen.

Leukocytic pyrogen previously reported to contain an essential protein moiety, appears to be a lipid-protein complex having a molecular weight in the range of 10,000 to 20,000. Evidence that it contains essential lipid includes its inactivation by Cu(++), its lability in alkaline solutions (pH 8.5 and above), and its loss of pyrogenicity when extracted with acid-isooctane. Its solubility in 66% methanol, and the enhancing action of ethanol in freeing it from sonicated cells, suggest the presence of exposed lipid groups at its surface. Once the complex is separated from other proteins, its biological activity is readily destroyed. Although the lipid component is presumed to contain unesterified fatty acid(s), its precise composition is unknown. The finding of lipid in the active complex is in keeping with the hypothesis that the pyrogen is derived from leukocytic membranes.

Fever↗
PubMed1967

Studies on the pathogenesis of fever. XV. The production of endogenous pyrogen by peritoneal macrophages.

Macrophages from oil-induced peritoneal exudates in rabbits produce endogenous pyrogen when first activated by incubation in 4 hr exudate fluid and then stimulated by incubation in potassium-free isotonic sodium chloride solution. The failure of earlier investigators to obtain pyrogen from macrophages is explained, and the relevance of macrophage pyrogen to fevers of agranulocytosis and other diseases, in which mononuclear rather than granulocytic exudates predominate, is discussed.

Animals↗
PubMed1970

Studies on the pathogenesis of fever. 18. Activation of leukocytes for pyrogen production.

Blood leukocytes, in contrast to exudate leukocytes, release little or no pyrogen when incubated in 0.15 M NaCl unless previously activated by exposure to endotoxin or to a protein activator that is present in acute exudate fluid. The activation process, which also occurs during phagocytosis, involves the synthesis of cellular protein, presumably related to the pyrogen molecule. Evidence is presented that generation of pyrogen in sterile inflammatory lesions depends on both the activator and the anaerobic conditions in the exudate fluid.

Animals↗
PubMed1970

Studies on the pathogenesis of fever. XX. Suppression and regeneration of pyrogen-producing capacity of exudate granulocytes.

Suppression of the pyrogen-producing capacity of exudate granulocytes results from incubation of the cells in plasma, serum, or Ringer's solution. When transferred in this state and incubated in isotonic NaCl, the cells release much less pyrogen than untreated exudate cells. The suppressive effect is reversible and appears to involve the cellular uptake of calcium ions. In contrast, regeneration of pyrogen-producing capacity in depleted exudate cells occurs only when the cells are incubated in serum. The process resembles activation and requires the cellular synthesis of protein.

Blood↗
PubMed1993

Group B streptococcal toxic shock-like syndrome: report of a case and purification of an associated pyrogenic toxin.

A patient with streptococcal toxic shock-like syndrome (TSLS) caused by Streptococcus agalactiae (group B Streptococcus) is described. The patient had all of the defining criteria for toxic shock syndrome (TSS), including fever, hypotension, erythematous rash, desquamation, and involvement of multiple organs. Neither Staphylococcus aureus nor group A streptococci were recovered, but vaginal and urine cultures yielded group B streptococci. The group B streptococcal isolate gave negative results in antibody tests for the production of TSS toxin 1, staphylococcal enterotoxins, and streptococcal scarlet fever toxins. However, the strain produced a novel pyrogenic toxin. This toxin, purified from culture fluids by ethanol precipitation, isoelectric focusing, and reverse-phase high-pressure liquid chromatography, had a molecular weight of 12,000 and an isoelectric point of approximately 7.0. The purified toxin was pyrogenic in rabbits, enhanced the susceptibility of the animals to lethal endotoxin shock, and caused the proliferation of rabbit splenocytes; these properties define pyrogenic toxins. When given to three rabbits via a subcutaneous miniosmotic pump, the toxin caused TSS-like symptoms ending in death. Three additional group B streptococcal strains from patients with TSLS were tested and were found to produce a toxin with similar properties.

Adult↗
PubMed1978

Effects of homologous O-antibody on host responses to lipopolysaccharide from Yersinia enterocolitica: neutralization of its pyrogenicity.

The pyrogenic activity of lipopolysaccharide (LPS) obtained from Yersinia enterocolitica was neutralized by the homologous O-antiserum at the optimal antigen/antibody ratio. The level of neutralization in either antigen excess or extreme antibody excess was significantly lower than that at the optimal ratio. These facts suggested that the structure of the so-called "lattice" of LPS/antibody complex might influence the neutralization of pyrogenic activity. Moreover, when LPS was gradually added to the antiserum to reach the optimal antigen/antibody ratio, the pyrogenic activity of LPS was only slightly neutralized by the antibody. The similar event to Danysz phenomenon that has been known in the diphtheria toxin-antitoxin system was also observed in the LPS-anti-LPS system.

Animals↗
PubMed1975

The effect of various amine-depleting drugs on the fever response exhibited by rabbits to bacterial or leucocyte pyrogen.

1 The concentration of noradrenaline, dopamine and 5-hydroxytryptamine (5-HT) in the rabbit brainstem was measured during fevers produced by either an injection of bacterial pyrogen (BP) or continuous infusion of leucocyte pyrogen (LP). 2 Both procedures had little effect on the concentration of noradrenaline in the preoptic/hypothalamic area but significantly (P smaller than 0.001) lowered the concentration of noradrenaline in the midbrain and pons/medulla. 3 BP significantly (P smaller than 0.01) lowered the concentration of 5-HT in the preoptic/hypothalamic area but had no effect in the midbrain or pons/medulla, whereas LP significantly (P smaller than 0.01) lowered the concentration of 5-HT in the midbrain and pons/medulla but had little effect in the hypothalamus. 4 The concentration of dopamine throughout the brainstem was little affected by either BP or LP fevers. However the concentration in the midbrain was significantly reduced by LP (P smaller than 0.001). 5 Alpha-Methyltyrosine (200 mg/kg) pretreatment diminished the pyrogenic response to both BP and LP whilst p-chlorophenylalanine (300 mg/kg) slightly enhanced the response to both forms of challenge. 6 Reserpine (1 mg/kg) diminished both types of fever whilst a combination of alpha-methyltyrosine and p-chlorophenylalanine slightly enhanced the fevers produced by either BP or LP. 7 The results obtained are discussed in relation to the mechanisms involved in the production of fever and to the possible function of noradrenaline and 5-HT as thermoregulatory transmitters.

Amines↗
PubMed1984

Renal excretion of prostaglandin metabolites, arginine vasopressin, and sodium during endotoxin and endogenous pyrogen induced fever in the goat.

Responses to intravenous injections of an endotoxin (E. coli-lipopolysaccharide, 1 microgram/kg b.wt.) and endogenous pyrogen were studied in euhydrated and hyperhydrated goats. The biphasic febrile response to the endotoxin was associated with a pronounced increase in the renal excretion of measured prostaglandin (PG) metabolites (11-ketotetranor PGF metabolites). This increase was time-correlated with the elevation of the rectal temperature, and (in hyperhydrated animals) with an inhibition of the water diuresis and an increase in renal excretion of arginine vasopressin (AVP). Other effects of the endotoxin were an immediate depression of renal Na and K excretion followed by the development of pronounced natriuresis, and a reduction of plasma Fe and Zn concentrations. The appearance of the febrile reactions (peripheral vasoconstriction and shivering) was accompanied by miosis. The maximum elevation of the rectal temperature was significantly greater during euhydration than during hyperhydration. Also endogenous pyrogen elicited miosis concomitant with febrile reactions, and an elevation of the renal excretion of PG metabolites which was closely correlated in time with the monophasic febrile response, and (during hyperhydration) with temporary inhibition of the water diuresis and an increase in the renal AVP excretion. However, the responses were much weaker than the corresponding endotoxin effects. No appreciable changes in renal excretion of Na and K were observed in response to the endogenous pyrogen. It is concluded that the observed effects on renal cation excretion were manifestations of direct endotoxin influences on kidney function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1981

A comparative study on the performance of asbestos-free depth-filters for removal of pyrogens from infusion fluids.

Three asbestos-free depth-filters were compared with traditionally used asbestos-containing depth-filters for chemical integrity, physical integrity and pyrogen retention. With chemical and physical integrity only minor differences between the various filter types were seen. One asbestos-free depth-filter, based on charcoal, showed poor pyrogen-retention; this might be due to a high flow rate used. Asbestos-free depth-filters based on kieselguhr or on a mixture of kaolin and alumina proved to be good alternatives; these filters have proved to be suitable for the removal of pyrogens from electrolyte- or carbohydrate-containing infusion fluids.

Chemical Phenomena↗
PubMed1973

Pyrogen fever and prostaglandin-like activity in cerebrospinal fluid.

1. In the unanaesthetized cat, rectal temperature was recorded and c.s.f. was collected from a Collison cannula implanted into the third ventricle with its opening lying in close proximity to the anterior hypothalamus. Samples of c.s.f. were collected from the same cat, during normal temperature, during fever produced by Shigella dysenteriae injected into the third ventricle and during the fall in temperature which occurred when the antipyretic paracetamol was injected intraperitoneally during the pyrogen fever.2. The samples of c.s.f., when tested on the rat stomach fundus preparation, caused contractions which were not due, or at most to a small degree only, to 5-hydroxytryptamine, as they were resistant to BOL. They were therefore probably due to a prostaglandin-like substance.3. When assayed against PGE(1), the activity of c.s.f. collected from cats when their body temperature was normal corresponded to between 1.3 and 10 ng/ml. The values, whether low or high, rose over 2.5-4 times to between 4 and 35 ng/ml. in c.s.f. collected during pyrogen fever; they were again low, between 1.5 and 6 ng/ml., in samples collected when the fever had been brought down by paracetamol, but rose again with the return of fever.4. The results provide direct evidence for the theory that fever produced by pyrogens results from their ability to increase synthesis and release of prostaglandins, and that antipyretics bring down the fever because they inhibit the increased synthesis.

Acetaminophen↗
PubMed1976

Effects of atropine, injected into a lateral cerebral ventricle of the rabbit, on fevers due to intravenous leucocyte pyrogen and hypothalamic and intraventricular injections of prostaglandin E1.

1. Cholinergic synapses in the hypothalamus may transmit information in those thermoregulatory pathways which function to raise body temperature. The effect of atropine, administered intracranially, on the febrile response to intravenous leucocyte pyrogen or intracranial prostaglandin E1 was therefore examined in conscious rabbits. 2. In rabbits exposed to a thermoneutral environment, micro-injections of PGE1, into the anterior hypothalamus, intraventricular injections of PGE1, and intravenous injection so leucocyte pyrogen all caused fever accompanied by vasoconstriction in the ears and reduced respiratory rate. Intraventricular injection of 200 mug atropine during such fevers attenuated their development. This was due to the activation of heat loss mechanisms through vasodilatation in the ears and an increase in the frequency of respiration. This suggests a similarity in the pattern of neuronal activity evoked by PGE1 and leucocyte pyrogen, at least at the site(s) where atropine directly or indirectly exerted its effect and in the efferent pathways from this site. 3. In rabbits exposed to a cold environment, intraventricular injection of PGE1 caused fever through the activation of shivering accompanied by increased O2 consumption. Intraventricular injection of atropine during the development of fever caused an inhibition of shivering accompanied by increased O2 consumption. Intraventricular injection of atropine during the development of fever caused an inhibition of shievering and a decrease in O2 consumption so that temperature ceased to rise and returned to normal. 4. During fever, reversal by atropine of the increased heat conservation of rabbits in a neutral environment, and of their increased heat production in a cold environment adds further support to the concept that cholinergic synapses provide an important link in central temperature-rasising pathways.

Animals↗