PubMed Health⌕ Search

Biomedical subjects

W Kozak

Publications and source records attributed to W Kozak.

At least 19 recordsLinked to original sources
PubMed1998

Endotoxin tolerance does not alter open field-induced fever in rats.

Exposure to an open field has been shown to cause a rise in the body temperature of rats. In many respects, this rise in body temperature is similar to fevers caused by endotoxin and other inflammatory stimuli. Rats repeatedly injected with endotoxin develop tolerance to the fever-inducing action of endotoxin. We hypothesized that repeated pretreatment with endotoxin would modify the fever caused by exposure to psychological stress. To test this hypothesis, we compared open field-induced fevers in rats made endotoxin tolerant to those rats not endotoxin tolerant. We found that endotoxin tolerance had no effect on open field fevers.

Animals↗
PubMed1998

The use of knockout mice to understand the role of cytokines in fever.

1. In most instances, data obtained using knockout mice to dissect the role of cytokines in fever are similar to data obtained by other, more traditional experimental techniques. 2. Interleukin (IL)-1beta appears to be critically involved in fever caused by some routes of infection/inflammation (e.g. localized inflammation with turpentine). This cytokine has only a small role in fevers caused by i.p. injection of lipopolysaccharide (LPS). These IL-1beta-induced fevers in knockout mice appear to be via the induction of IL-6, similar to LPS-induced fevers in rats. Interleukin-6 also appears to be critically involved in turpentine-induced fever. 3. The precise role of tumour necrosis factor (TNF) in fever is controversial. Data obtained from knockout mice lacking both TNF receptors do not support a pyrogenic role for TNF in fever either to i.p. injection of LPS, s.c. injection of turpentine or following caecal ligation and puncture. 4. The roles of these cytokines in fevers induced by injection of LPS, IL-1beta, turpentine and caecal ligation and puncture are summarized. The data show the complexity of the febrile response. Depending on the types of inflammatory/infectious stimuli, different cytokines play important roles. Because other cytokines are thought to be involved in fever (e.g. macrophage inflammatory protein, interferons), considerable work is still needed to dissect the precise roles of cytokines in fever.

Animals↗
PubMed1997

Thyroid volume and function in patients with acromegaly living in iodine deficient areas.

The aim of our study was to evaluate the size and function of the thyroid in patients with acromegaly. In 39 patients concentrations of HGH, PRL, TSH, T3 and T4 were measured and the thyroid volume was calculated with the using of ultrasound examination. The control group comprised 5 patients with acromegaly in a stage of remission and 98 controls. We concluded that the size of the goiter in patients with acromegaly depends on serum concentration of HGH, but it does not depend on the concentration of TSH, T3, T4 and PRL. Goiter is present in 87% of patients with acromegaly, 46% of them are nodular goiters. The thyroid function in acromegaly is normal.

Acromegaly↗
PubMed1997

Exacerbated febrile responses to LPS, but not turpentine, in TNF double receptor-knockout mice.

We examined the effects of injections of systemic [lipopolysaccharide (LPS), 2.5 mg/kg or 50 pg/kg ip] or local (turpentine, 100 microl sc) inflammatory stimuli on fever, motor activity, body weight, and food intake in tumor necrosis factor (TNF) double receptor (TNFR)-knockout mice. A high dose of LPS resulted in exacerbated fevers in TNFR-knockout mice compared with wild-type mice for the early phase of fever (3-15 h); the late phase of fever (16-24 h) and fevers to a low dose of LPS were similar in both groups. Motor activity, body weight, and food intake were similarly reduced in both groups of mice after LPS administration. In response to turpentine, TNFR-knockout and wild-type mice developed virtually identical responses to all variables monitored. These results suggest that 1) TNF modulates fevers to LPS dose dependently, 2) TNF does not modulate fevers to a subcutaneous injection of turpentine, and 3) knockout mice may develop cytokine redundancy in the regulation of the acute phase response to intraperitoneally injected LPS or subcutaneously injected turpentine.

Animals↗
PubMed1997

Sickness behavior in mice deficient in interleukin-6 during turpentine abscess and influenza pneumonitis.

Interleukin-6 (IL-6), among other cytokines, is thought to be involved in the regulation of sickness behavior (e.g., anorexia, cachexia, fever, and lethargy) induced by infections bacterial and viral origin) and sterile tissue necrosis (burns and surgical traumas). Mice deficient in IL-6 (IL-6 KO) were generated by gene targeting. Homozygous IL-6 KO male and female mice and their appropriate controls were implanted with biotelemeters to monitor body temperature (Tb) and motor activity (Act). Normal circadian rhythms in Tb and Act as well as rates of food intake and weight gain did not differ significantly between sex-matched IL-6 KO and control groups at 30 degrees C in a 12:12-h light-dark cycle. Sterile tissue damage was induced in mice by subcutaneous injection of turpentine (0.1 ml, left hindlimb). Influenza pneumonitis was induced by intranasal inoculation of mouse-adapted influenza A virus (17.5 plaque-forming units). Lack of IL-6 completely prevented fever, anorexia, and cachexia because of turpentine abscess in both sexes. It did not prevent lethargy, although IL-6 KO mice recovered to normal Act significantly sooner than wild-type mice. Symptoms of sickness were only slightly modified during influenza virus infection in IL-6 KO mice. Attenuation of sickness behavior was more pronounced in IL-6 KO female than in male mice. We conclude that, although IL-6 is induced during both turpentine abscess and influenza infection, this cytokine appears to be more critical in induction of the symptoms of sickness behavior during sterile tissue abscess than during influenza infection.

Abscess↗
PubMed1997

Dietary n-3 fatty acids differentially affect sickness behavior in mice during local and systemic inflammation.

We tested the hypothesis that increased dietary fish oil levels (via modulation of the production of inflammatory mediators) modulate sickness symptoms (i.e., anorexia, cachexia, fever, lethargy) of systemic and local inflammation. Swiss Webster mice were implanted with biotelemeters to measure body temperature and motor activity and were fed a diet high in n-3 fatty acids (17% wt/wt menhaden oil) or a reference diet (17% wt/wt hydrogenated coconut oil or normal rodent chow) for 6 wk. Local inflammation was induced by subcutaneous injection of turpentine (100 microl/mouse). Systemic inflammation was elicited by intraperitoneal injection of lipopolysaccharide (LPS; 2.5 mg/kg). Fever, lethargy, anorexia, and weight decrease during turpentine abscess were all inhibited (P < 0.05) in mice fed the fish oil diet. Indomethacin, similar to the fish oil diet, attenuated the turpentine-induced symptoms in mice fed a normal diet. Dietary n-3 fatty acids prevented fever and attenuated the decrease in body weight caused by LPS but did not affect the LPS-induced lethargy and anorexia. Within 90 min of LPS injection, the bioactivity of plasma tumor necrosis factor-alpha (TNF-alpha) increased to 98.2 +/- 5.1 ng/ml in mice fed fish oil compared with 32.6 +/- 3.6 ng/ml in those fed the reference diet (P < 0.05). Plasma prostaglandin E2 (PGE2) levels after LPS injection of mice fed the control diet increased within 90 min to 16.4 +/- 5.1 pg/ml. Mice fed the fish oil diet did not show any elevation in plasma PGE2 levels at that time (P < 0.05). We speculate that dietary n-3 fatty acids suppressed PGE2-related responses, including a PGE2-dependent negative feedback on TNF-alpha production, which resulted in differential modulation of sickness behavior depending on the locus of inflammation.

Animals↗
PubMed1997

Effect of heat stress on LPS-induced fever and tumor necrosis factor.

Exposure to heat stress leads to both short-term and long-term effects on morbidity. Male rats were exposed to a high ambient temperature of 40 degrees C, which resulted in biotelemetered core body temperature rising to approximately 42 degrees C. This treatment led to a marked enhancement in lipopolysaccharide (LPS)-induced fever at 24 h after exposure to heat stress. The increase in fever was accompanied by a significant suppression in the circulating concentration of tumor necrosis factor. Heat-shock protein-70 measured in liver was elevated by the heat exposure (but not further elevated by the injection of LPS). An enhanced fever to LPS and other inflammatory stimuli found in heat-stressed human subjects could explain the apparent increase in susceptibility to disease.

Animals↗
PubMed1997

Attenuation of lipopolysaccharide fever in rats by protein kinase C inhibitors.

The purpose of this study was to assess the effects of inhibitors of protein kinase C (PKC) on lipopolysaccharide (LPS)-induced fever and changes in circulating interleukin-6 (IL-6) levels in freely moving biotelemetered rats. We used PKC inhibitors with different inhibition constants (Ki): H-7 (Ki = 6 microM) and chelerythrine (Chel; Ki = 0.66 microM; a more potent PKC inhibitor). Rats were injected subcutaneously with either 3 or 15 microM/kg of these inhibitors and then 1 h later were injected intraperitoneally with LPS (50 micrograms/kg). Blood samples for IL-6 bioassay were collected 4 h after LPS injection. H-7 at lower doses did not significantly affect fever and LPS-induced elevation of circulating IL-6, whereas at a higher dose (15 microM/kg) H-7 reduced both fever and the increase of IL-6 (analysis of variance, Scheffé's test, P < 0.05). Chel (3 and 15 microM/kg) significantly reduced fever and almost completely inhibited the LPS-induced elevation of plasma IL-6. In separate experiments, we studied the effect of H-7 on antipyresis due to dexamethasone (Dex). Dex at a dose of 0.6 microM/kg given subcutaneously 1 h before LPS partially prevented fever (approximately 55% inhibition) and attenuated the increase of IL-6 (P < 0.05). Simultaneous pretreatment of the rats with Dex and H-7 (3 microM/kg; a dose that did not affect fever and IL-6 elevation) led to a potentiation of the antipyretic effect of Dex, resulting in no fever. H-7 did not potentiate, however, the inhibitory effect of Dex on LPS-induced elevation of circulating IL-6. We conclude that PKC is involved in the regulation of LPS fever and constitutes a rate-limiting factor in modulation of the fever by glucocorticoids.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1996

Hypoxia decreases opioid delta receptor expression in mouse brain.

Delta opioid receptor activation is protective during hypoxic injury. Many adaptive responses occur during exposure to hypoxia to facilitate survival. It is possible that increased activity of the delta opioid receptor system is one such adaptation. We tested the hypothesis that mice exposed to prolonged hypoxia have increased expression of the delta opioid receptor in brain tissue. Prolonged exposure to hypoxia (9% oxygen, balance nitrogen) continuously for seven days selectively decreased delta opioid receptor expression in mouse brain homogenate. The same hypoxic treatment had no effects on either mu or kappa opioid receptor expression, indicating that this response was not due to non-selective degradation of protein. Shorter term hypoxic treatments (one day and three days) did not induce changes in delta opioid receptor expression in whole brain homogenate. Binding assays were also conducted in grossly dissected brain regions (cortex, midbrain, hindbrain) to determine whether the shorter term treatments would induce changes in receptor expression in more discrete areas. No consistent changes in delta opioid receptor expression were detected in these brain regions. These data demonstrate that opioid delta receptors are hypoxia sensitive and may be a part of an adaptive process to increase survival in the organism. One possible cause for the decrease in delta opioid receptor expression following seven days of hypoxic exposure may be receptor down-regulation caused by an increased release of endogenous substances acting at delta receptors. As delta opioid receptor agonists appear promising for therapeutic potential in management of hypoxic injury, changes in delta receptor expression in response to long-term hypoxia could impact potential utilization of delta agonists in patients suffering chronic hypoxia.

Animals↗
PubMed1996

The adaptive value of fever.

There is overwhelming evidence in favor of fever being an adaptive host response to infection that has persisted throughout the animal kingdom for hundreds of millions of years. As such, it is probable that the use of antipyretic/anti-inflammatory/analgesic drugs, when they lead to suppression of fever, results in increased morbidity and mortality during most infections; this morbidity and mortality may not be apparent to most health care workers because fever is only one of dozens of host defense responses. Furthermore, most infections are not life-threatening and subtle changes in morbidity are not easily detected.

Adaptation, Physiological↗
PubMed1996

Adrenalectomy--still a must in radical renal surgery?

OBJECTIVE: To investigate the incidence of adrenal involvement and survival in patients with renal cell carcinoma. PATIENTS AND METHODS: A retrospective, multicentre trial was initiated by the Austrian Association of Urologic Oncology (AUO); between January 1980 and December 1984, 225 patients were eligible for the study. All patients had unilateral renal tumours and nephrectomies were performed either with (group A, 109 patients) or without (group B, 116 patients) adrenalectomy. The two groups were matched for sex, age, laterality and nodal status. The mean follow-up time was 78 months. RESULTS: The location of the intrarenal tumour had no significant effect on adrenal involvement. By univariate and multivariate analysis (Cox's proportional hazards model) significant differences in outcome were found only for pT stages. The mean survival times of patients in group A were 122.9 months in those with stage pT1/2, 76.6 months with stage pT3 and 75.3 months with stage pT4. In group B, survival times were 109 months in those with stage pT1/2 (not significant) and 111 months in stage pT3 (P = 0.0076). Eight patients had adrenal involvement and died from their tumours after a median of 15.3 months (range 4-63). The slightly longer survival of patients in group B with stage T1/2 tumours and the significantly better survival of patients with stage T3 disease may be attributable to statistical bias, but there was no benefit from adrenalectomy. CONCLUSION: The effect of adrenalectomy on the prognosis was at best comparable to that of lymphadenectomy and no curative effect was demonstrated. The removal of a healthy adrenal may be detrimental and cause subsequent problems in those patients requiring hormone replacement.

Adrenalectomy↗
PubMed1996

Beta-adrenoceptor antagonists suppress elevation in body temperature and increase in plasma IL-6 in rats exposed to open field.

The purpose of these studies was to assess the involvement of beta-adrenoceptors in the development of psychological stress-induced elevation in body temperature (Tb) and rise in circulating interleukin-6 (IL-6). We selected three drugs to attempt to block the rise in body temperature and plasma IL-6; L-propranolol, D-propranolol and nadolol. Both stereoisomers of propranolol have "local anesthetic' membrane-stabilizing activity and are capable of penetrating into the brain. However, D-propranolol has significantly lower beta-blocking activity than L-propranolol. Nadolol has beta-blocking activity similar to L-propranolol without membrane-stabilizing activity. Furthermore, nadolol does not cross the blood-brain barrier. All beta-blockers were injected intraperitoneally (i.p. 7.5 mg/kg) or into the third cerebral ventricle (i.c.v., 5 or 50 micrograms/animal), 20 min or just before exposure of rats to an open field, respectively. Blood samples for measurement of plasma IL-6 activity (IL-6-dependent B9 cell bioassay) were taken from rats immediately following exposure to the open field. After exposure to the open field, rats not treated with beta-blockers responded with a rapid rise in Tb measured by biotelemetry as well as with an increase in plasma IL-6 activity. The increase in Tb of open field-exposed rats was significantly suppressed by L-propranolol injected i.p. (delta Tmax = 0.14 +/- 0.15 degrees C for L-propranolol vs. 0.78 +/- 0.15 degrees C for vehicle-treated rats). Neither i.p. injection of D-propranolol nor nadolol had any effect on the increase in Tb induced by exposure to the open field. Both i.c.v. doses of L-propranolol and nadolol markedly attenuated the open field-induced rise in Tb. The large i.c.v. dose of D-propranolol (50 micrograms) did, whereas the lower dose (5 micrograms) did not suppress the elevation in Tb in open field exposed rats. The open field-exposed rats injected with L-propranolol (both i.p. or i.c.v.) had lower plasma IL-6 activity than that of open field-exposed rats injected with vehicle (for i.p. injection: 5.2 +/- 1.3 U/ml for L-propranolol vs. 17.4 +/- 3.8 U/ml for vehicle; for i.c.v. injection: 3.5 +/- 2.3 U/ml for L-propranolol vs. 24.4 +/- 7.2 U/ml for vehicle). Nadolol blocked the open field-induced rise in plasma IL-6 only when injected i.c.v. but no i.p. Neither i.p. nor i.c.v. D-propranolol injection had an effect on plasma IL-6 activity in open field-exposed rats. These data show that beta-adrenoceptors in the central nervous system are involved in the psychological stress-induced elevation in Tb and rise in plasma IL-6 activity caused by exposure to an open field.

Adrenergic beta-Antagonists↗
PubMed1996

[Correlation between the clinical stage of larynx cancer in male and female and levels of steroid hormones in serum].

264 patients with cancer of larynx, 21 female and 234 male, had a testosterone and sex hormone binding globulin (SHBG) before the treatment in serum estimated. Because of dependence of levels of hormones the group of patients was divided into three following groups: "lower than standard", "standard", "higher than standard". The correlation between these groups and sex, age, localization of tumor, organs' advances, stage of morphological malignancy and type of cancer was reported. Anomalous values of testosterone were in male group more frequently reported. Anomalous values of SHBG were similar in male and female groups, but in the female group there was a significant majority of "lower than standard" values reported. The majority of abnormal values of testosterone and SHBG was described in groups of age higher than 50 years. There were no differences in testosterone and SHBG levels in different localization of tumors in larynx. In advanced stage T3 and T4 there were more frequent lower mean values of testosterone levels and higher values of SHBG levels in comparison to T2 stages. In tumors in G1 and G2 stages of histological malignancy higher levels of SHBG and higher mean levels of testosterone. The tumors in stage G3 the hormone levels were lowers were observed. The levels of SHBG in groups of carcinoma planoepitheliale keratodes were in 66% higher than in a group of carcinoma planoepitheliale akeratodes but in both groups the levels of testosterone were nearing the same. In group of patients with larynx cancer the negative correlation between the levels of testosterone and SHBG was not observed. Higher SHBG levels were not always accompanied by lower testosterone levels.

Adult↗
PubMed1996

[Radioimmunologic methods for determining cortisol binding globulin-CBG in human serum].

The authors described double antibodies radioimmunoassay of human cortisol binding globulin serum level in support of previous isolated and purified trancortin and anti-transcortin antibodies produced by rabbit immunization. Antigen was iodinated by chloraminet method and purification on Ultragel AcA 54 column. Standard curve had specific Bx/Box100%. Using described method investigation of transcortin globulin serum level is precise and repetitive.

Carrier Proteins↗
PubMed1995

Body temperature, motor activity, and feeding behavior of mice treated with beta-chlornaltrexamine.

The effects of an irreversible long term opioid antagonism on circadian rhythms in body temperature (Tb), locomotor activity (Act) and feeding under normal conditions and following lipopolysaccharide administration (LPS; 2.5 mg/kg) have been investigated in unrestrained mice housed at their thermoneutral zone (30 degrees C). beta-chlornaltrexamine (beta-CNA; 5 mg/kg) given intraperitoneally decreased Tb on the day of injection, depressed Act, and reduced food and water intake for several days. The drug destroyed circadian rhythm in Tb for 4 consecutive days after administration due to prevention of the night time increases in temperature, whereas mean day time Tb of mice treated with beta-CNA remained similar to controls. Between days 5-8 the day-time Tb of beta-CNA-injected mice decreased, and the mice started displaying regular daily variations albeit with smaller amplitude and at lower level than controls. The depressive effect of beta-CNA on circadian variation in activity was more prolonged than its effect on Tb suggesting that these two variables are independently regulated. beta-CNA prevented the febrile response of the mice to LPS and enhanced the hypophagic effect of LPS. We conclude that normal circadian rhythms in Tb and Act, as well as certain symptoms of sickness behavior, have an opioid component.

Animals↗