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Biomedical subjects

W Kozak

Publications and source records attributed to W Kozak.

At least 55 records · Page 3Linked to original sources
PubMed1995

Resistance to fever induction and impaired acute-phase response in interleukin-1 beta-deficient mice.

We used gene targeting in embryonic stem cells to introduce an IL-1 beta null allele in mice. The IL-1 beta-deficient mice develop normally and are apparently healthy and fertile. The IL-1 beta null mice responded normally in models of contact and delayed-type hypersensitivity or following bacterial endotoxin LPS-induced inflammation. The IL-1 beta-deficient mice showed equivalent resistance to Listeria monocytogenes compared with wild-type controls. In contrast, when challenged with turpentine, which causes localized inflammation and tissue injury, the IL-1 beta mutant mice exhibited an impaired acute-phase inflammatory response and were completely resistant to fever development and anorexia. These results highlight a central role for IL-1 beta as a pyrogen and a mediator of the acute-phase response in a subset of inflammatory disease models, and support the notion that blocking the action of a single key cytokine can alter the course of specific immune and inflammatory responses.

Acute-Phase Reaction↗
PubMed1995

Systemic but not central administration of tumor necrosis factor-alpha attenuates LPS-induced fever in rats.

The purpose of this study was to test the hypothesis that tumor necrosis factor-alpha (TNF) limits fever induced by lipopolysaccharide (LPS) in rats and to determine whether such antipyretic action of this cytokine is outside or inside the central nervous system (CNS). The CNS effects on LPS-induced fever were tested by injecting a subpyrogenic amount (0.20 microgram) of human recombinant TNF (hrTNF) intracerebroventricularly or by slowly infusing into the anterior hypothalamus an amount previously measured in this brain region during LPS fever (0.24 U in 0.13 microliter of artificial cerebrospinal fluid/min). The peripheral effects of this cytokine on LPS fever were tested by injecting 1 micrograms/kg of hrTNF intraperitoneally or by intraperitoneal administration of 300 micrograms/kg of the hrTNF soluble receptor p80 (hrTNFsr). The core temperature (measured by biotelemetry) during LPS fever was not significantly affected by administration of hrTNF intracerebroventricularly or intrahypothalamically. An intraperitoneal injection of hrTNF (1 microgram/kg) had a significant antipyretic effect on febrile response to LPS (mean temperature 2-8 h after injections was 37.28 +/- 0.12 degrees C in rats injected with hrTNF and LPS vs. 38.73 +/- 0.04 degrees C in rats injected with saline and LPS; analysis of variance among groups, P = 0.0001; Fisher's protected least significant difference, P < 0.05). When rats were injected intraperitoneally with hrTNFsr, the febrile response to LPS was enhanced (analysis of variance among groups, P = 0.0001; Fisher's protected least significant difference, P < 0.05). These results support the hypothesis that TNF acts to limit the magnitude of LPS-induced fever and that this action occurs outside the CNS.

Analgesics, Non-Narcotic↗
PubMed1995

TNF soluble receptor and antiserum against TNF enhance lipopolysaccharide fever in mice.

We tested the effects of tumor necrosis factor (TNF) soluble receptor (sTNFR) and anti-TNF serum (anti-TNF) administered intraperitoneally on fever induced by lipopolysaccharide (LPS) in mice. Both agents have been shown to block bioactivity of mouse TNF-alpha. Core temperature (Tb) and locomotor activity in unrestrained mice were measured by biotelemetry. Within 1 h from the LPS injection (2.5 mg/kg ip) Tb decreased below normal for 5-6 h and motor activity was depressed for the following 48 h. After this initial reduction, Tb increased and reached a peak at approximately 24 h postinjection. Anti-TNF and sTNFR blocked this "hypothermic phase" after LPS, and the fevers started sooner; however, the levels and time of peak temperature did not change markedly. In addition, a human recombinant TNF-alpha given intraperitoneally abolished fever and prolonged the fall of Tb in mice after LPS. We conclude that the reduction of Tb soon after injection of LPS in mice is dependent on TNF-alpha.

Animals↗
PubMed1995

Thermal and behavioral effects of lipopolysaccharide and influenza in interleukin-1 beta-deficient mice.

This study characterized body temperature (Tb), locomotor activity (Act), and feeding behavior under normal conditions and following injection with lipopolysaccharide (LPS) or inoculation with live influenza virus of transgenic C57/black mice deficient in interleukin-1 beta (IL-1 beta). Tb and Act in freely moving mice were measured by biotelemetry. Mice deficient in IL-1 beta had normal circadian rhythm of Tb but were less active than their control counterparts. Mice injected with LPS (2.5 mg/kg i.p.) responded with a prompt decrease of Tb, which lasted approximately 10 h, followed by a fever in which Tb reached a peak at approximately 24 h postinjection. There was no difference between groups in the early drop of Tb after the LPS; however, the 24-h peak of Tb was lower in IL-1 beta-deficient mice. The anorexic effects of LPS and influenza infection were similar in both groups of mice. In mice given influenza virus (17.5 plaque-forming units, median lethal dose), Tb and Act gradually decreased. The fall of Tb was smaller in the transgenic mice. The mice deficient in IL-1 beta displayed a higher mortality rate due to influenza infection than the control mice. We conclude that deficiency in IL-1 beta results in lower fever following the LPS injection and in impairment of the defense response to infection with influenza.

Animals↗
PubMed1994

Lipopolysaccharide induces fever and depresses locomotor activity in unrestrained mice.

The purpose of this study was to characterize the basic biology of fever to lipopolysaccharide (LPS) in unrestrained mice. Although LPS has been shown to induce fevers in many laboratory animals (e.g., rats, guinea pigs, rabbits), there is some question of whether LPS causes a fall or rise in body temperature (Tb) in mice. Tb was measured by biotelemetry in unrestrained mice maintained at an ambient temperature of 30 degrees C. Intraperitoneal injections of LPS at doses of 1.0, 2.5, and 3.0 mg/kg induced dose-independent prompt decreases of Tb for 5.7 h. After this postinjection reduction, Tb increased and reached a peak at approximately 24 h postinjection. The peak rises in Tb were dose dependent. Changes in Tb due to LPS were accompanied by suppression of locomotor activity. Indomethacin, at a dose that did not affect normal Tb, enhanced the temperature-lowering effect of LPS as well as inhibited the febrile rise of Tb after LPS. Indomethacin did not modify the reduction in activity caused by the injections of LPS. Food intake of the mice was decreased by LPS in a dose-dependent manner, and tolerance developed to a second injection of LPS. We conclude that freely moving mice can develop pronounced and reproducible fevers in response to LPS, which is different in time course, dose-dependent profile, induction of pyrogenic tolerance profile, and mode of inhibition by indomethacin from those responses that have been observed in other species studied so far.

Animals↗
PubMed1994

[Synthesis and characteristics of anti-CBG antibodies (anti-transcortin)].

We used corticosteroid binding globulin purified by chromatography on the Sepharose column for immunisation of the rabbits. We analysed serum by rocket immunoelectrophoresis and cross immunoelectrophoresis. The titre of the serum was estimated by reaction with 125 I-labelled transcortin (corticosteroid binding globulin). The results of our studies indicate that own serum is valuable and can be use for radioimmunoassay of the CBG in the serum.

Animals↗
PubMed1994

[Isolation and purification of transcortin (cortisol binding globulin--CBG) using two-step chromatography].

The isolation of cortisol and progesterone binding globulin (CBG) from pregnant women serum was performed using affinity and hydrophobic chromatography. The purity and specificity of isolated transcortin was tested by agarose gel electrophoresis using racket and cross immunoelectrophoresis and specific CBG antibodies. High purity and immunoreactivity of the isolated globulin destitute of other proteins contamination, were obtained.

Chromatography↗
PubMed1992

A moderate dose of cycloheximide does not prevent the febrile response to endotoxin but interfere with induction of pyrogenic tolerance in rabbit.

The purpose of the present study was to examine the effect of cycloheximide (Cx)--inhibitor of protein synthesis, on the development of pyrogenic tolerance to LPS. It has been observed that Cx at a dose of 1 mg/kg given intravenously 1 h prior to LPS did not prevent fever response, however it modified the induction of pyrogenic tolerance. It was manifested in existence of the second phase of fever after the following administrations of LPS into rabbits pretreated with Cx. In control group of rabbits the induction of pyrogenic tolerance was accompanied with decaying of the second peak of fever visible as early as the second dose of LPS.

Animals↗
PubMed1992

[Attempt of preventive treatment of striae gravidarum using preventive massage ointment administration].

Striae distensae are an appreciable cosmetic problem for many pregnant women. Preventive application of a water/oil massage cream was tested in a group of 24 gravidae (control group: 26 patients). In the untreated control group striae distensae were observed in two-thirds of the patients, whereas the prophylactically-treated gravidae showed development of striae in only one third of the group given the test preparation. Better results were obtained in women with a favourable constitutional predisposition than in patients with a tendency to overweight. The massage cream was well tolerated by all gravidae.

Adult↗
PubMed1992

[Fever as a homeostatic process accompanying infection].

After a survey of experimental data the author considers the notion that elevated (febrile) temperature acts as an adaptive factor buffering against the disordering of biomembrane homeostasis during infection. Impendance of the membrane homeostasis under infectious conditions occurs due to the certain disturbance of membrane structure caused by pyrogen-induced activation of phospholipases and liberation of arachidonic acid from phospholipid deposits. A consequence of liberation and oxygenation of the arachidonic acid is an outflow of double bonds from the overall pool embedded in the structure of membrane. This in turn leads to an increase of membrane bulk phase transition temperature and to depletion of membrane fluidity at normal (non-febrile) temperature.

Anti-Infective Agents↗
PubMed1991

Course of fever response to repeated administration of sublethal doses of lipopolysaccharides, polyinosinic:polycytidylic acid and muramyl dipeptide to rabbits.

The purpose of the present study was to examine the development of tolerance to three structurally dissimilar pyrogens, i.e., lipopolysaccharide (LPS), muramyl dipeptide (MDP) and polyinosinic:polycytidylic acid (poly I:C) in rabbits. The possibility of pyrogenic cross-tolerance among these agents has also been studied. It was observed that repeated injection of sublethal doses of LPS and MDP was connected with the changing of biphasic fever to monophasic. The consequence of this was a drop in the fever index. In contrast to LPS and MDP, the repeated administration of poly I:C did not result in such changes. Successive injections of this pyrogen always evoked biphasic fever. We also demonstrated that pyrogenic cross-tolerance between LPS and MDP did not occur. The cross-tolerance between LPS and MDP did not occur. The cross-tolerance among pyrogens was possible if they originated from the same class, for example endotoxin from Salmonella abortus eq. and endotoxin from Escherichia coli.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

Lack of pyrogenic tolerance transmission between brain and periphery in the rabbit.

Successive injections of lipopolysaccharide (LPS) either intravenously (i.v.) or intracerebroventricularly (i.c.v.) induced pyrogenic tolerance to LPS in rabbits. Tolerance was shown by a decrease of the magnitude of the fever response to repeated doses of LPS, irrespective of the route of pyrogen administration. A significantly greater and more dramatic decrease of the fever index, however, was observed in rabbits made tolerant to pyrogen given i.v. than when the pyrogen was given i.c.v. Transmission of the pyrogenic tolerance between brain and peripheral tissues, however, has not been ascertained.

Animals↗
PubMed1989

Lipopolysaccharide, muramyl dipeptide and polyinosinic: polycytidylic acid induce the accumulation of inositol phosphates in blood monocytes and lymphocytes.

Rabbit macrophages (Mø) and lymphocytes (Ly) incubated with three structurally dissimilar immunomodulators, lipopolysaccharide (bacterial endotoxin, LPS), polyinosinic: polycytidylic acid (poly-I:C) and muramyl dipeptide (MDP), were found to accumulate inositol phosphates (IPs) in a concentration- and time-dependent manner. The threshold concentration of LPS necessary for an increase in IPs in both cell types was less than 1 ng/ml and a maximum effect was observed between 1 and 10 micrograms/ml. The threshold concentrations for poly-I:C and MDP were between 0.1 and 1 microgram/ml for both cell types. Significant increases in the concentration of inositol phosphates occurred between 30 and 60 min after challenge of either cell type with any of the three agents studied. In addition, all three immunomodulators produced a greater accumulation of IPs in macrophages than in mixed lymphocytes and after 2 h appeared to approach a maximum in macrophages, whereas the IPs level in lymphocytes appeared to be still rising after 2 h. In Mø and Ly the IPs level was increased within 10 min of incubation in the presence of either PGE2 or medium previously obtained from cells incubated with LPS. In addition, anisomycin (a protein synthesis inhibitor) and ketoprofen (a cyclo-oxygenase inhibitor) inhibited the LPS-stimulated increase of IPs accumulation in both cell types. These two observations suggest that the LPS-stimulated increase in IPs in macrophages and lymphocytes is mediated by a protein intermediate and possibly a prostanoid.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1989

Exploratory behavior and the dual activity of some psychoactive drugs. Part 5. Alcohol.

Alcohol is reported to impair acquisition and learning processes and it is considered a depressant of the brain activities impairing rapidity and consistency of some behaviors. The experiments reported here are concerned with the exploratory performances of the already described subpopulations of Albino mice under the effect of alcohols of different types.

Alcoholic Beverages↗
PubMed1988

Non-invasive tests of neurovascular function: reduced axon reflex responses in diabetes mellitus of man and streptozotocin-induced diabetes of the rat.

The prevalence of neuropathy and microangiopathy complicating diabetes mellitus led to our development of non-invasive tests of neurovascular function. On the foot dorsum of consenting normal subjects, diabetic patients, normal and streptozotocin-induced (STZ) diabetic rats, transcutaneous electrical nerve stimulation (TENS) with 1, 2, 4, 8, 16 pulses at 150 V, 0.75 ms, at 2 Hz, evokes transient cutaneous axon reflex vasodilatation measured by a laser Doppler (Periflux Pfld). This tests the integrity of both the polymodal nociceptor/primary afferent nerves and microvessels in the skin. TENS-evoked axon reflexes are reduced in diabetics (particularly with neuropathy) and progressively in rats 40-100 days after STZ administration. This could be reversed in rats by a single injection of 3 units of soluble insulin at 100 days post STZ. The microvascular endothelium and smooth muscle are tested in man by measuring vasodilatation induced by iontophoretic application of 2 mC acetylcholine (ACh) and 4 mC sodium nitroprusside (NaNP), respectively. Diabetics show reduced ACh-evoked endothelium-dependent vasodilator responses, but the direct smooth muscle (endothelium-independent) responses evoked by NaNP are not reduced. Such functional neurovascular disturbances probably underlie many complications of diabetes mellitus, and the potential for these to be reversible with appropriate therapy can now be examined with such neurovascular tests.

Animals↗