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A pyrogen is a substance that causes fever after intravenous administration or inhalation. Gram negative endotoxins are the most important pyrogens to pharmaceutical laboratories. In the International, United States, Japanese and European Pharmacopoeias, there are two official methods to evaluate pyrogenicity—that is, the bacterial endotoxin test, and the pyrogen test. The main objective of this review is to compare the monographs of each test among the different Pharmacopeias, to detect similarities and differences. The former can be considered fully harmonized, and only non significant differences were detected. The latter, which is the only available assay for some products and formulations to demonstrate apyrogenicity, shows large differences, which should be considered., Depto. de Nutrición y Ciencia de los Alimentos, Fac. de Farmacia, TRUE, pub

Producción Científica, A pyrogen is a substance that causes fever after intravenous administration or inhalation. Gram negative endotoxins are the most important pyrogens to pharmaceutical laboratories. In the International, United States, Japanese and European Pharmacopoeias, there are two official methods to evaluate pyrogenicity—that is, the bacterial endotoxin test, and the pyrogen test. The main objective of this review is to compare the monographs of each test among the different Pharmacopeias, to detect similarities and differences. The former can be considered fully harmonized, and only non-significant differences were detected. The latter, which is the only available assay for some products and formulations to demonstrate apyrogenicity, shows large differences, which should be considered.

Producción Científica, A pyrogen is a substance that causes fever after intravenous administration or inhalation. Gram negative endotoxins are the most important pyrogens to pharmaceutical laboratories. In the International, United States, Japanese and European Pharmacopoeias, there are two official methods to evaluate pyrogenicity—that is, the bacterial endotoxin test, and the pyrogen test. The main objective of this review is to compare the monographs of each test among the different Pharmacopeias, to detect similarities and differences. The former can be considered fully harmonized, and only non-significant differences were detected. The latter, which is the only available assay for some products and formulations to demonstrate apyrogenicity, shows large differences, which should be considered., Sin financiación externa

Producción Científica, A pyrogen is a substance that causes fever after intravenous administration or inhalation. Gram negative endotoxins are the most important pyrogens to pharmaceutical laboratories. In the International, United States, Japanese and European Pharmacopoeias, there are two official methods to evaluate pyrogenicity—that is, the bacterial endotoxin test, and the pyrogen test. The main objective of this review is to compare the monographs of each test among the different Pharmacopeias, to detect similarities and differences. The former can be considered fully harmonized, and only non-significant differences were detected. The latter, which is the only available assay for some products and formulations to demonstrate apyrogenicity, shows large differences, which should be considered.

Producción Científica, A pyrogen is a substance that causes fever after intravenous administration or inhalation. Gram negative endotoxins are the most important pyrogens to pharmaceutical laboratories. In the International, United States, Japanese and European Pharmacopoeias, there are two official methods to evaluate pyrogenicity—that is, the bacterial endotoxin test, and the pyrogen test. The main objective of this review is to compare the monographs of each test among the different Pharmacopeias, to detect similarities and differences. The former can be considered fully harmonized, and only non-significant differences were detected. The latter, which is the only available assay for some products and formulations to demonstrate apyrogenicity, shows large differences, which should be considered.

De veehouderijsector streeft naar minder gebruik van antibiotica en is naarstig op zoek naar nieuwe behandelmethoden om bacteriële infecties de baas te kunnen. Is slangengif de oplossing?

Pyrogens are substances that may induce fever in the human body. They can be parts of bacteria, virus or fungi and due to the reaction they may cause in the body, they are routinely looked for in the medical technology industries. A method called in vitro pyrogen test (IPT) has been developed to detect these pyrogens. It is based on the fever reaction in the human body and only requires blood in combination with a solution believed to contain pyrogens. If the result is positive, the production of cytokines is started. The cytokines of interest in the IPT method are those involved in the fever process and two of them are IL-1β and TNF-α, which are the cytokines used as markers of infection in this study. Since the production of cytokines is in proportion to the amount of pyrogens, the inflammation-inducing potential of the sample can be decided. Due to problems in standardizing the method, mainly because it handles with living blood cells, focus is still pointed at improving it. The aim of this study was to optimize parameters within the IPT method by analysing air samples taken in indoor surroundings believed to contain pyrogens. The different parameters included extraction of the filter from the air sampling, incubation of whole blood and sample extract and analysis of the incubation with ELISA (enzyme linked immunosorbent assay). More specific, some of the issues concerned extraction media, time and shaking intensity for the extraction, blood ratio for the whole blood incubation and cytokines suitable for the method. A possible approach for the IPT method, when analysing air samples containing pyrogens, was reached., Pyrogener kallas ämnen som framkallar feber och de kan exempelvis bestå av hela eller delar av bakterier, virus eller svamp (fungi). En metod som kallas för in vitro pyrogen test (IPT) har utvecklats för att detektera dessa pyrogener. Metoden bygger på att en lösning som misstänks innehålla pyrogener får komma i kontakt med blod från en människa. Efter en inkubering på mellan 4-24 timmar har blodet reagerat på eventuella pyrogener och bildat cytokiner, där mängden cytokiner är proportionell mot mängden pyrogener. De intressanta cytokinerna i den här studien var IL-1β och TNF-α, som båda är involverade i feberprocessen. Det har varit svårigheter med att standardisera metoden, mycket beroende på att det är levande celler som hela metoden bygger på, så syftet med den här studien var att förbättra in vitro pyrogen test. Luftprover tagna i inomhusmiljöer som misstänks innehålla pyrogener har använts i försöken att optimera varje steg i processen. De olika stegen inkluderade extraktion av filter som använts vid luftprovtagningen, inkubering med helblod och provextrakt och analys av inkuberingen med ELISA (enzyme linked immunosorbent assay). Några av de parametrar som undersöktes gällde extraktionsmedium, skaktid och skakintensitet under extraktionen, blodförhållande under helblodsinkuberingen och lämpliga cytokiner för metoden. Studien resulterade i att en metodik, för att analysera luftprov innehållande pyrogener med in vitro pyrogen test, kunde tas fram.

The blood-CSF barrier (BCSFB) in choroid plexus works with the blood-brain barrier (BBB) in cerebral capillaries to stabilize the fluid environment of neurons. Dysfunction of either transport interface, i.e., BCSFB or BBB, causes augmented fluxes of ions, water and proteins into the CNS. These barrier disruptions lead to problems with edema and other compromised homeostatic mechanisms. Hyperthermic effects on BCSFB permeability and transport are not as well known as for BBB. However, it is becoming increasingly appreciated that elevated prostaglandin synthesis from fever/heat activation of cyclooxygenases (COXs) in the BCSFB promotes water and ion transfer from plasma to the ventricles; this harmful fluid movement into the CSF-brain interior can be attenuated by agents that inhibit the COXs. Moreover, new functional data from our laboratory animal model indicate that the BCSFB (choroidal epithelium) and the CSF-bordering ependymal cells are vulnerable to whole body hyperthermia (WBH). This is evidenced from the fact that rats subjected to 4h of heat stress (38 degrees C) showed a significant increase in the translocation of Evans blue and (131)Iodine from plasma to cisternal CSF, and manifested blue staining of the dorsal surface of the hippocampus and caudate nucleus. Degeneration of choroidal epithelial cells and underlying ependyma, a dilated ventricular space and damage to the underlying neuropil were frequent. A disrupted BCSFB is associated with a marked increase in edema formation in the hippocampus, caudate nucleus, thalamus and hypothalamus. Taken together, these findings suggest that the breaching of the BCSFB in hyperthermia significantly contributes to cell and tissue injuries in the CNS.

Pyrotechnically generated fire extinguishing aerosols represent an alternative to halon fire extinguishers in enclosed spaces. This study reviewed existing literature on one specific type (Pyrogen) and assessed the potential health risks associated with a short-term (15 min) exposure to a Pyrogen discharge. A fairly extensive study of vapor phase components by the Russian Academy of Science suggested that concentrations of potentially hazardous gases were generally below levels of concern. However, ammonia and N2 may pose some concern because concentrations exceeded recognized short-term exposure limits. Specific composition of the hydrocarbons produced also merit further study as they may or may not represent an additional inhalation risk. Concentrations of solid phase particulates generated by Pyrogen appear to be well below any levels of concern given their reported chemical composition.

In the monocytic cell line Mono Mac 6 pyrogens induce interleukin-6 secretion dose dependently. The aim of this study is to examine the interleukin-6 inducing capacity of Gram positive Staphylococcus aureus and Bacillus subtilis endospores after moist and dry heat sterilisation. Moist heat sterilisation of B. subtilis endospores for 15 min at 121 degrees C and 134 degrees C can only reduce the interleukin-6 inducing capacity to 57% and 63%, respectively, compared to untreated. Moist heat sterilisation of S. aureus for 60 min at 121 degrees C and 134 degrees C does not reduce the interleukin-6 inducing capacity of S. aureus. On the contrary moist heat sterilisation at 134 degrees C for 10, 20 and 40 min significantly increases the interleukin-6 inducing capacity compared to untreated S. aureus. This is confirmed in the rabbit pyrogen test. Dry heat sterilisation of B. subtilis endospores at 220 degrees C for 45 min reduces the interleukin-6 inducing capacity to 2% compared to untreated endospores. Dry heat treatment of S. aureus at 220 degrees C for 30 min only reduces the activity to 55%. However, after 250 degrees C for 30 min or 220 degrees C for 6h there is no detectable activity of S. aureus. In conclusion, neither the interleukin-6 inducing activity nor the pyrogenicity of S. aureus and endospores of B. subtilis can be inactivated by the heat sterilisation procedures described by the European Pharmacopoeia.

In the monocytic cell line Mono Mac 6 pyrogens induce interleukin-6 secretion dose dependently. The aim of this study is to examine the interleukin-6 inducing capacity of Gram positive Staphylococcus aureus and Bacillus subtilis endospores after moist and dry heat sterilisation. Moist heat sterilisation of B. subtilis endospores for 15 min at 121 degrees C and 134 degrees C can only reduce the interleukin-6 inducing capacity to 57% and 63%, respectively, compared to untreated. Moist heat sterilisation of S. aureus for 60 min at 121 degrees C and 134 degrees C does not reduce the interleukin-6 inducing capacity of S. aureus. On the contrary moist heat sterilisation at 134 degrees C for 10, 20 and 40 min significantly increases the interleukin-6 inducing capacity compared to untreated S. aureus. This is confirmed in the rabbit pyrogen test. Dry heat sterilisation of B. subtilis endospores at 220 degrees C for 45 min reduces the interleukin-6 inducing capacity to 2% compared to untreated endospores. Dry heat treatment of S. aureus at 220 degrees C for 30 min only reduces the activity to 55%. However, after 250 degrees C for 30 min or 220 degrees C for 6h there is no detectable activity of S. aureus. In conclusion, neither the interleukin-6 inducing activity nor the pyrogenicity of S. aureus and endospores of B. subtilis can be inactivated by the heat sterilisation procedures described by the European Pharmacopoeia.

The monocytic cell line Mono Mac 6 is sensitive to pyrogens. When exposed to pyrogens secretion of interleukin-6 is induced. However, some eukaryotic pyrogenic microorganisms are not detectable. The aim of this study is to introduce a pretreatment of samples to expand the detection range of the assay. The interleukin-6 inducing capacity of a broad spectrum of UV-killed and ultrasonicated microorganisms is examined in Mono Mac 6 cells. The interleukin-6 secretion is determined in a sandwich immunoassay (DELFIA). The Mono Mac 6 assay is able to detect UV-killed Bacillus subtilis, Staphylococcus aureus and Salmonella typhimurium, but neither Candida albicans nor Aspergillus niger. After ultrasonication of the microorganisms it is possible to detect C. albicans and A. niger. The interleukin-6 inducing ability of the examined microorganisms is in no case reduced after ultrasonic treatment. However, ultrasonication of S. aureus results in a 100-fold increase in the interleukin-6 response. Even after ultrasonication Streptococcus faecalis can not be detected. Ultrasonication is an easy and simple method for expanding the detection range in the Mono Mac 6 assay.

The monocytic cell line Mono Mac 6 is sensitive to pyrogens. When exposed to pyrogens secretion of interleukin-6 is induced. However, some eukaryotic pyrogenic microorganisms are not detectable. The aim of this study is to introduce a pretreatment of samples to expand the detection range of the assay. The interleukin-6 inducing capacity of a broad spectrum of UV-killed and ultrasonicated microorganisms is examined in Mono Mac 6 cells. The interleukin-6 secretion is determined in a sandwich immunoassay (DELFIA). The Mono Mac 6 assay is able to detect UV-killed Bacillus subtilis, Staphylococcus aureus and Salmonella typhimurium, but neither Candida albicans nor Aspergillus niger. After ultrasonication of the microorganisms it is possible to detect C. albicans and A. niger. The interleukin-6 inducing ability of the examined microorganisms is in no case reduced after ultrasonic treatment. However, ultrasonication of S. aureus results in a 100-fold increase in the interleukin-6 response. Even after ultrasonication Streptococcus faecalis can not be detected. Ultrasonication is an easy and simple method for expanding the detection range in the Mono Mac 6 assay.

Pyrogen induced secretion of interleukin 6 (IL-6) in Mono Mac 6 (MM6) cells was measured. The ability of the MM6 cell culture to detect pyrogens was compared to the Limulus amoebocyte lysate (LAL) test and isolated mononuclear cells (MNC). The detection limit of MM6 for lipopolysaccharide (LPS) and Staphylococcus aureus was comparable to that of MNC. Aspergillus niger and Candida albicans induced IL-6 in isolated MNC, but not in MM6. The detection limit for Salmonella typhimurium in the MM6 assay was comparable to that of the LAL assay. As expected, S. aureus and C. albicans did not show any LAL activity. A. niger and Influenza virus showed some activity in the LAL test, but could not be detected by MM6 cells. In conclusion, the MM6 assay is a good supplement to the current pyrogen assays for detection of LPS, S. aureus and S. typhimurium, but the MM6 assay could not detect A. niger, C. albicans and Influenza virus.

Pyrogen induced secretion of interleukin 6 (IL-6) in Mono Mac 6 (MM6) cells was measured. The ability of the MM6 cell culture to detect pyrogens was compared to the Limulus amoebocyte lysate (LAL) test and isolated mononuclear cells (MNC). The detection limit of MM6 for lipopolysaccharide (LPS) and Staphylococcus aureus was comparable to that of MNC. Aspergillus niger and Candida albicans induced IL-6 in isolated MNC, but not in MM6. The detection limit for Salmonella typhimurium in the MM6 assay was comparable to that of the LAL assay. As expected, S. aureus and C. albicans did not show any LAL activity. A. niger and Influenza virus showed some activity in the LAL test, but could not be detected by MM6 cells. In conclusion, the MM6 assay is a good supplement to the current pyrogen assays for detection of LPS, S. aureus and S. typhimurium, but the MM6 assay could not detect A. niger, C. albicans and Influenza virus.

Pyrogen induced secretion of interleukin 6 (IL-6) in Mono Mac 6 (MM6) cells was measured. The ability of the MM6 cell culture to detect pyrogens was compared to the Limulus amoebocyte lysate (LAL) test and isolated mononuclear cells (MNC). The detection limit of MM6 for lipopolysaccharide (LPS) and Staphylococcus aureus was comparable to that of MNC. Aspergillus niger and Candida albicans induced IL-6 in isolated MNC, but not in MM6. The detection limit for Salmonella typhimurium in the MM6 assay was comparable to that of the LAL assay. As expected, S. aureus and C. albicans did not show any LAL activity. A. niger and Influenza virus showed some activity in the LAL test, but could not be detected by MM6 cells. In conclusion, the MM6 assay is a good supplement to the current pyrogen assays for detection of LPS, S. aureus and S. typhimurium, but the MM6 assay could not detect A. niger, C. albicans and Influenza virus.

Measurement of lipopolysaccharide (LPS) induced interleukin-6 (IL-6) secretion in Mono Mac 6 cells.

Measurement of lipopolysaccharide (LPS) induced interleukin-6 (IL-6) secretion in Mono Mac 6 cells.

An electrochemical based Advanced Oxidation Process (AOP) developed by Lynntech, Inc., was used to produce USP pharmaceutical grade Water For Injection (WFI) by decomposing pyrogen, oxidizing dissolved organics and sterilizing the final product water. Electrochemical generation of ozone is emerging as an advanced technology because: (1) ozone is formed directly from water and (2) this method provides a concentrated ozone source surpassing that of conventional ozone generation processes. By combining ozone generation with UV radiation in an AOP system design, enhanced oxidation results from the chemical radicals produced through the interaction of UV light with ozone. These transient radicals aggressively attack and oxidize a diverse range of chemicals (i.e., benzene, acetic acid, pyrogallol, etc). This project entailed: (1) fabrication and testing of an ozone generation module, (2) assembly and testing of an 03 + UV treatment system, (3) purification of water by oxidation of organic contaminants, (4) ozone sterilization, and (5) demonstrating that an electrochemical ozone generation module can be easily converted to an electrochemical oxygen generation module. These applications illustrate a widespread use potential. Lynntech has advanced this electrochemical technology to a suitable stage for scaleu to a commercial prototype. Details of cost benefits are included. Electrochemical ozone generation, Advanced ozonation process, Water purification, Ozone oxidation, Sterilization.

A small, disposable system has been developed to prepare USP Sterile Water for Injection (WFI) from a pressurized potable source. The system comprises, in series, a standard laboratory strong acid/strong base ion exchange column, an activated carbon water purification filter, a fine particle filter, a 0.2 um sterilizing filter and a Resuscitation Fluids Production System (REFLUPS) 18 L bag set, which is filled by means of a 19-port distribution head. This system is capable of generating sterile, pyrogen-free water at a fill rate of 0. 5 L/min. Product resistivity did not consistently meet the 1.0 megohm limit corresponding to the USP standard for dissolved salts; a second, smaller, ion exchange cartridge will be required.

U937 is a cell line derived from a human histiocytic lymphoma. This cell has some of the properties of macrophages. It elaborates factors that effect normal human hematopoiesis. It can be activated by supernatants of mixed lymphocyte cells or by 12-tetradecanoylphorbol-13 acetate to exhibit several properties associated with macrophages: myeloid morphology, binding of the chemotactic peptide fMet-Leu-Phe, antibody-dependent cell cytotoxicity, and Fc- receptor activity. The cells also have strong esterase activity, produce lysozyme and endogenous pyrogen, are phagocytic, and bear receptors for complement and IgG. We have used the U937 cell line for the analysis of human macrophage structure and function. Sixteen monoclonal antibodies which bind to the surface of U937 cells have been obtained. Nine proteins were identified by immunoprecipitation, and the distribution of the antigens among blood cells was determined using flow cytofluorimetric analysis. This chapter describes the initial characterization and identification of the antigenic targets of this panel of antibodies. Keywords: Reprints., Pub. in Cell Fusion: Gene Transfer and Transformation, p325-344 1984.

Previous research on sleep-promoting substances that accumulate in cerebrospinal fluid during wakefulness led to the discovery of the somnogenic activity of muramyl peptides (MPs). Our broad goal is to develop information needed to ascertain if MPs or other endogenous sleep factors would be practical as somnogenic agents. We report on: 1) Murametide, an MP that induces interleukin-1 (IL1) production but also blocks IL1-induced fevers, potentiated IL1-induced fever and sleep when given at the same time as IL1. In contrast, when IL1 was given 30 min after murametide, murametide completely blocked IL1- induced fevers but still potentiated IL1-induced sleep. 2) Previously, we proposed that MP induced sleep via a step involving IL1 production. IL1 also induces corticotropic-releasing factor (CRF) release, which leads to enhanced adreno-corticotropic hormone (ACTH) release and glucocorticoid release. Last year we showed that alpha melanocyte-stimulating hormone (i.e., ACTH(1-13)) blocked IL1-induced sleep responses. Since it was known that glucocorticoids turn off IL1 production, we tested CRF in combination with IL1. CRF blocked IL1- enhanced sleep. 3) Several of the cytokines whose production are enhanced by MPs, IL1, interferon alpha2, and tumor necrosis factor, are pyrogenic and somnogenic. 4) We showed that prolactin and two of its hypothalamic releasing factors, selectively enhanced REM sleep. (edc)

In normal as well as hypovolemic awake dogs, cardiac output can be increased significantly by infusion of ATP-MgCl2 intravenously at rates of 0.5-2.5mg/kg/min. The higher doses of ATP-MgCl2 may have detrimental hemodynamic effects, however, such effects are immediately reversible by ceasing ATP-MgCl2 infusion. Moreover, the deleterious hemodynamic effects of very high doses of ATP-MgCl2 can be markedly ameliorated by atropine. Infusion of ATP-MgCl2 did not affect hepatic or renal function, myocardium or blood chemistry after infusion or even after a prolonged period of time. Infusion of even massive doses of ATP-MgCl2 have no ill effects on the survival of dogs.

Intracerebroventricular (icv) injection of endogenous pyrogen (EP) into rats causes dose-related fever. To compare this procedure with the usual assay method, iv injection into rabbits, a preparation of crude rabbit EP was titrated by both methods. The rat icv injcetion procedure gave results simil in linearity and magnitude of response to the conventional rabbit iv method, but was found to be at least 50-fold more sensitive. The icv assay worked for human as well as rabbit EP and for partially purified as well as crude preparations. Plasma from human or animal sources did not interfere. The rat icv and rabbit iv assay methods were also compared in their ability to detect a pyrogen in filter-sterilized plasma from rats infected with the live vaccine strain (LVS) of Francisella tularensis. The rat icv method gave fevers of 1 deg with 0.05-ml samples of the filtered plasma from infected rats, but no fever with plasma from control rats. The pyrogen was partially purified from the infected rat plasma. It was found to be heat labile and nondialyzable, and was tentatively identified as rat EP. The less esnsitive rabbit assay was unable to detect the plasma pyrogen using 0.05- and 1.00-ml samples. These observations suggest that icv injection into rats is a useful and sensitive assay method for EP, particularly when only small volumes are available for testing., Published in the Proceedings of the Society for Experimental Biology and Medicine, v166 p6-11, 1981. Supersedes report dated 12 Dec 1979, ADA082933.

Human and rabbit endogenous pyrogens bind to affinity columns of both Cibacron Blue agarose and its carboxymethyl derivative. All pyrogenic activity from both sources is recovered by eluting with a high salt concentration buffer. This affinity chromatographic step purified crude rabbit endogenous pyrogen 5-fold (from 118 to 588 rat pyrogen doses/mg) or gel filtered rabbit pyrogen 10-fold (up to 5,820 rat pyrogen doses/mg). (Author)

Relapsing fever caused by Borrelia spirochetes is characterized by episodes of spirochetemia, fever, and disseminated intravascular coagulation (DIC). We examined the ability of Borrelia hermsii, which does not contain endotoxin, to induce production of leukocytic pyrogen and thromboplastin from human blood leukocytes in vitro. Cultures of B. hermsii were washed with pyrogen-free saline. Mononuclear cells (MNC) were separated from blood by Ficoll-Hypaque gradient sedimentation and incubated with 2-5 spirochetes per MNC in 10% human serum. Supernatants from 5 times 10 to the 7th power cells were assayed in rabbits for fever production. Intact MNC were simultaneously assayed for thromboplastin activity with a modified one-stage prothrombin time employing normal human plasma and plasma deficient in individual coagulation factors. Supernatants of the MNC-spirochete mixtures produced mean increases in temperature of 0.80-1.35 deg C, which were significantly higher than supernatants of MNC, 0.13 deg C, or spirochetes alone, 0.10 deg C (p less than 0.05). MNC-spirochete mixtures possessed 7 to 15 times the thromboplastin activity of MNC suspensions. Promotion or inhibition of phagocytosis by adding respectively immune rabbit serum or cytochalasin B did not alter production of leukocytic pyrogen or thromboplastin.

This chapter reviews the nature of hormonal responses during infectious illnesses. It describes the short-lived adrenocortical response, the biphasic thyroid response, the minimal catecholamine response in the absence of shock, the combined insulin-glucagon response and the variable responses by individual pituitary hormones. Concepts discussed include the severity and duration of infections, differences related to the kind of infection, and endocrine-associated complications of infection.

The physiological mechanisms by which fever is produced in man and experimental animals have, for many years, intrigued medical practitioners and basic physiologists. Body tissue do not normally contain transferable fever-producing substances. If, however, phagocytic cells are activated by certain stimuli, they may synthesize pyrogenic factors of endogenous origin. First recognized about three decades ago, these endogenous substances were found to initiate the onset of fever if injected into a suitable assay animal. A variety of factors are produced and released from circulating leukocytes or tissue macrophages when these cells are stimulated either by pyrogenic substances or by engaging in phagocytic activity. Although initially called granulocytic or neutrophilic pyrogen, the fever-producing factors of cellular origin are now gennerally known as endogenous pyrogen, or EP. The entire field of body temperature regulation has been stimulated by the recent discovery that many cold-blooded animal species increase their internal body temperatures as a purposeful response to an experimental inoculation of pathogenic bacteria. Cold-blooded animals (and some infant mammals) increase their internal temperature by moving to a warmer environment. This form of behavioral fever is analagous to the development of clinical fever during the course of infectious or inflammatory processes in man. These exciting discoveries and the additional demonstrations that fever may be of benefit in terms of host survival have led to a renewed interest in fever and its underlying mechanisms. This interest is evidenced, in part, by the fact that the American Physiological Society has sponsored two recent symposia on this topic., Supersedes report dated 10 Dec 1979, ADA082841. Tutorial Lecture presented at the Fall Meeting, 1979, New Orleans.

Supersedes report dated 3 Apr 79, AD-A068 792.

The production and testing of pyrogen-free water under field conditions, such as in the Pharmacy Module of Army Mobile Unit Self-Transportable Hospitals (MUST), presents serious problems because of volume requirements, power constraints, and quality control requirements. This report defines these problems and makes recommendations concerning: the development of a treatment system to produce pyrogen-free water from potable water; the evaluation of an in vitro biological test to determine apyrogenicity in the field; and evaluation of a handling and storage system for field-produced pyrogen-free water. (Author)

Antileucocytic serum (ALS) administered to rabbits produced a marked effect on the content of leucocytes in blood and brought about a rise in body temperature. Addition of ALS to whole rabbit blood leads to the accumulation of endogenous pyrogens in the plasma. Results of this study confirm the possible dependence of pyretic reactions in immunopathological processes on the formation of endogenous pyrogens during the interaction of specific antibodies and leucocytes., Trans. of Byulleten Eksperimentalnoi Biologii i Meditsiny (USSR) v75 n10 p77-80 1973.

The effects of pyrogens on the relationship between thermoregulatory salivation and hypothalamic temperature were studied in the resting and exercising dog at different environmental temperatures. The slope and threshold of the curve of salivation versus hypothalamic temperature were decreased in three afebrile dogs during exercise as compared to rest. With fever there was increase in the threshold for salivation both at rest and at 6.4 kilometers per hour at ambient temperature of 15C, 25C, and 35C. The slope of the salivation response curves at these ambient temperatures during fever was increased during rest and either unchanged or increased during exercise. (Modified author abstract)

The condition of furnace fuel oils in long-term shore storage, pumping trials conducted in depot pipe lines and limited trials in ships are described. Considerable difficulties were experienced in organising sea trials as the ships which could be allocated for the purpose all had other commitments of higher priority and the information obtained was therefore very limited. The large scale pumping trials in depots were sufficiently comprehensive and a good deal of information became available as a result. These trials inevitably suffer from the disadvantage that the temperature of the fuel cannot be adjusted to any required level before the trial and pipelines during the trial are exposed to the prevailing air temperatures. In addition, the pipes may have been in use for some years and their internal condition can only be imagined. It was decided that a rig should be constructed which would be large enough to reproduce the actual conditions which might exist in a small ship, yet be small enough for the essential parts to be housed in a cold room., ADM-62-325

Contents: Macrophage Factor of Blood; Mercurial Diuretics; Cytology of the Human Nasal Mucosa.

Prospective clinical studies in volunteers have shown that experimentally-induce bacterial or viral infections induce alterations early in the prodromal period in a variety of anabolism-related metabolic processes. Studies in experimental animals and man have shown that the mechanisms leading to these host changes were mediated by an endogenous humoral factor which enters the serum. This heat labile endogenous mediator, like endogenous pyrogen, was released by PMN leukocytes and possibly other cells after the initiation of a generalized infection. Endogenous mediator may prove to be a key intermediate in stimulation of various non-specific host defense mechanisms.

This report discusses a system for field preparation of electrolytic solutions using prepackaged, dried electrolyte and field production of water for injection, utilizing a small, man-packable, light-weight assembly of items suitable for field use in preparing sterile, pyrogen-free solutions for intravenous use., See also Volume 2, AD-683 473.

The report gives test results on the water purification system as discussed in Vol. I, AD-683 472., See also Volume 1, AD-683 472.

A continuous temperature monitoring system was employed in rabbits which utilized a subcutaneously placed copper-constantan thermocouple attached to a direct drive recorder. It has the following advantages over the previous method of rectal temperature determinations. It was more reliable, less subject to environmental variations resulting from animal handling and substantially reduced the technician time required by the other method. (Author)

The use of a new apparatus has resulted in obtaining both uniform films and crystallites. It was determined that intermediate substrate temperatures (1050 -1100 C) will lead to uniform silicon films if certain conditions are met. The study of the effects of post-deposition heat treatment on sputtered III-V compounds was continued. Numerous arsenide films were sputtered and their electrical properties examined. Work was begun on the sputtering of silicon carbide. The films obtained varied greatly in their properties. The thickness dependence of the dielectric constants of films of CeO2, SiO2, and Si3N4, was investigated. Films of CeO2 and SiO2 showed the dielectric anomaly. Films of numerous materials were vacuum deposited. Films of lead and cadmium sulfide, selenide and telluride, zinc oxide and sulfide, and tin oxide were formed. Many all-deposited, layered field effect devices were formed and, their characteristics determined. Significant improvement in device parameters was achieved. Voltage-amplification factors as high as 600 were obtained. Tunnel diodes were formed in silicon crystallites. (Author)

This report includes: Fullam, Ernest F., Inc., Schenectady, N. Y. ELECTRON DIFFRACTION ANALYSIS OF EVAPORATED FILMS. 9 July 62. Research continued on thin-film circuits and systems in which electronic circuit elements are integrated in a material matrix to a point where individual elemental appearances have been lost. The circuits will be capable of operating at 500 C., and should possess a high degree of radiation resistance. The circuits, as conceived, will contain microareas within a single film and/or be formed of layers of metals, semiconductors, and dielectrics in preconceived conceived configurations to provide the necessary electronic functions. The objective is to be accomplished by performing studies of film and microcrystal formation, surface and interfacial phenomena, and geometric studies of configurations to use, to the maximum advantage, the physical effects that occur in thin films. The electronic circuits so formed will possess a maximum degree of microminiaturization. (Author)

The patent describes a portable stainless steel water distillation unit capable of producing sterile, pyrogen-free water in a single distillation. A filtering section permits the use of deionizing resin or activated charcoal. A series of baffles permit the incoming water to be preheated by a portion of the steam. Another series of baffles filter out particulate matters from the steam on its way to the condensation chamber where it is effectively cooled but isolated from the feed water. The relationship of the elements enables the compact, durable unit to function at maximum thermal efficiency.

The physiologic consequences of hyperpyrexia attracted considerable interest when artificially-induced fever was a popular therapeutic maneuver.