Jana Jurcovicova - Academia.edu (original) (raw)
Papers by Jana Jurcovicova
Behavioural Brain Research, 2003
SUMMARY 1. The aim of this study was to compare the effects of acute amphetamine (AMPH) treatment... more SUMMARY 1. The aim of this study was to compare the effects of acute amphetamine (AMPH) treatment and restraint stress on plasma level of prolactin (PRL) and PRL mRNA expression in the adenohypophysis in Sprague-Dawley and Lewis male rats, the latter known to have a deficient hypothalamo-pituitary-adrenal (HPA) axis. 2. Both restraint stress and AMPH treatment (i.p. in a dose of 8 mg/kg of b.w.) were applied 15 or 30 min before termination of the experiment. Plasma PRL and corticosterone (CORT) were determined by radioimmunoassay. PRL mRNA expression was estimated by a dot-blot hybridization. 3. Restraint stress and AMPH treatment induced a significant increase in the CORT plasma level, as an indicator of stress response. Compared to Sprague-Dawley rats, the magnitude of CORT increase after both stimuli was significantly lower in Lewis rats. 4. Although restraint stress significantly increased the PRL plasma levels in both rat strains, AMPH treatment reduced the PRL levels in both r...
Endocrine regulations, 2006
OBJECTIVE Proinflammatory cytokines IL-1beta, and IL-6 are synthesized in the brain, where they e... more OBJECTIVE Proinflammatory cytokines IL-1beta, and IL-6 are synthesized in the brain, where they exert local regulatory functions. Our aim was to find out whether, along with the activation of hypothalamo-pituitary-adrenocortical (HPA) axis and prolactin (PRL), the acute systemic enhancement of IL-1beta affects its own production in the hypothalamus as well as that of IL-6. METHOD Forty five minutes after a single i.p. administration of recombinant rat IL-1beta (5 microg/kg) to male Long Evans rats we estimated the expression of IL-1beta and IL-6 mRNA in the hypothalamus by real time PCR, ACTH, corticosterone (CORT), and PRL by RIA RESULTS: IL-1beta administration stimulated the expression of IL-1beta mRNA in the hypothalamus by 99 %, but not that of IL-6. It also significantly activated plasma levels of ACTH, PRL, CORT, and CORT production in adrenal gland. CONCLUSION These results indicate that acute peripheral enhancement of IL-1beta may induce neuroendocrine changes also via the ...
Journal of Cachexia, Sarcopenia and Muscle
Background: Sarcopenia is defined as loss of skeletal muscle mass and function. In clinical resea... more Background: Sarcopenia is defined as loss of skeletal muscle mass and function. In clinical research, measurement of skeletal muscle mass index (SMI) is based on appendicular skeletal muscle mass (kg)/height 2 (m 2) <2 SD below the mean of a young reference group. 1 SMI was found to be associated with increased physical disability independent of age, ethnicity, comorbidity, and fat mass. 2 Alternatively, SMI is reported as weight-adjusted SMI derived from values obtained from bioelectrical impedance analysis. 3 A recent study suggests the height-adjusted SMI has better correlation with reduced muscle strength and gait speed. 4 Methods: We assessed data on 2521 women with a variety of medical conditions who presented to a tertiary hospital for assessment of bone mineral density (BMD). Some of these women also had concurrent body composition and anthropometry performed. Aims: We aim (i) To determine the relationship between BMD, body composition, and anthropometry in the whole group and subgroups. (ii) To determine The relationship between age and decline in skeletal muscle mass and its relationship to anthropometric variables. (iii) To explore leg length (which appears constant with age) vs. height (which declines with age) in standardizing skeletal muscle measurement for body size. Results: Participants were females aged 40-97 years (mean 59 years). The majority of the patients who were referred presented on a background of breast cancer (n = 679, 27.9%), followed by screening or other causes (n = 563, 22.3%) and steroid use (n = 241, 9.6%). When analysed on regression variable plots, reduction in sitting height, biceps, thigh skin fold, total body, femoral neck BMD, and T score occurs with age. Discussion: There were no changes observed in leg length with age. This suggests that leg length may be used as an alternative to height in the calculation of skeletal muscle mass index.
Neuroimmunomodulation, 2004
Several interleukins (ILs) including IL-1 beta and IL-6 are produced in the anterior pituitary (A... more Several interleukins (ILs) including IL-1 beta and IL-6 are produced in the anterior pituitary (AP) where they probably participate in the local regulation of hormone production. Immune challenge brings about the dysregulation of immune-endocrine interaction and enhanced the expression of pituitary IL-1 beta and IL-6. Little is known about regulation of their production, and therefore the purpose of the present work was to describe the relationship between circulating corticosterone and the mRNA expression of proopiomelanocortin (POMC), IL-1 beta and IL-6 in the AP during a 24-hour cycle in normal rats and rats with acute adjuvant arthritis (AA). Groups of intact male Long-Evans rats and rats 23 days after induction of AA kept on a 12-hour light/dark cycle (light on at 6:00 a.m.) were killed at 4-hour intervals starting at 2:00 p.m. Trunk blood was used for corticosterone determination by radioimmunoassay. Adenopituitaries were extracted for total RNA and the message of interest was quantitated by real-time PCR using specific primers and TaqMan probes. Parameters of rhythms were evaluated by cosinor analysis. In normal rats, serum corticosterone showed a circadian rhythm with the peak at 6:00 p.m. and the nadir in the morning hours (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). POMC mRNA in AP also showed a circadian rhythm (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) which was inversely related to corticosterone levels. IL-1beta and IL-6 expression in normal rats showed clear-cut daily rhythms (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) with the nadirs in the dark period, in contrast to the corticosterone peak in plasma. In arthritic rats, rhythmic corticosterone secretion was suppressed with a plateau pattern of the rhythm. The mean POMC expression was higher than in controls, and the rhythm failed to be significant. IL-1 beta expression was suppressed by AA (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) but the rhythm was still present (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). The rhythmic pattern of IL-6 expression was similar to that of controls, but with higher mesor values (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). These results suggest a regulatory relationship between circulating corticosterone and the expression of POMC, IL-1 beta and IL-6 in AP of normal rats. Arthritis induced a higher expression of POMC and IL-6 in the AP and a suppression of IL-1 beta mRNA during the 24-hour cycle which suggests the involvement of different regulatory mechanisms compared to normal conditions.
Brain Research Bulletin, 1989
We studied the effects of adjuvant arthritis (AA) on the endocrine circadian rhythms of plasma pr... more We studied the effects of adjuvant arthritis (AA) on the endocrine circadian rhythms of plasma prolactin (PRL), growth hormone (GH), insulin-like growth factor-1 (IGF-1), luteinizing hormone (LH), testosterone, and melatonin and of pituitary PRL and GH mRNA in male Long Evans rats. Groups of control and AA rats (studied 23 days after AA induction) that were housed under a 12/12 h light/dark cycle (light on at 06:00 h) were killed at 4 h intervals starting at 14:00 h. Cosinor analysis revealed a significant 12 h rhythm in PRL and PRL mRNA (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) in controls with peaks at 14:00 h and 02:00 h, respectively. The peak at 02:00 h was abolished in the AA group resulting in a significant 24 h rhythm in parallel with that of PRL (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) and PRL mRNA (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Growth hormone showed no rhythm, but a significant rhythm of GH mRNA was present in both groups (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Insulin-like growth factor-1 showed a 24 h rhythm in control but not in AA rats. The mean values of GH, GH mRNA, and IGF-1 were significantly reduced in AA. Luteinizing hormone displayed a significant 24 h rhythm (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) peaking in the dark period in the control but not AA group. Testosterone showed in phase temporal changes of LH levels with AA abolishing the 02:00 h peak. Melatonin exhibited a significant 24 h rhythm in control (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and AA (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) rats with maximum levels during the dark phase; the mesor value was higher in the AA males. These results demonstrate that AA interferes with the rhythms of all the studied hormones except the non-24 h (arrhythmic) GH secretion pattern and the rhythm in melatonin. The persistence of a distinct melatonin rhythm in AA suggests the observed disturbances of hormonal rhythms in this condition do not occur at the level of the pineal gland.
Molecular and Cellular Endocrinology, Mar 1, 2010
11-Hydroxysteroid dehydrogenase 1 (11HSD1) regulates local glucocorticoid activity and plays an ... more 11-Hydroxysteroid dehydrogenase 1 (11HSD1) regulates local glucocorticoid activity and plays an important role in various diseases. Here, we studied whether arthritis modulates 11HSD1, what is the role of pro-inflammatory cytokines in this process and whether altered local metabolism of glucocorticoids may contribute to the feedback regulation of inflammation. Adjuvant arthritis increased synovial 11HSD1 mRNA and 11-reductase activity but treatments with tumor necrosis factor ␣ (TNF-␣) and interleukin 1 (IL-1) antagonists etanercept and anakinra reduced 11HSD1 upregulation. Treatment with carbenoxolone, an 11HSD inhibitor, increased expression of TNF-␣, cyclooxygenase 2, and osteopontin mRNA without any changes in the plasma levels of corticosterone. Similar changes were observed when arthritic rats were treated with RU486, an antagonist of GR. This study suggests that arthritis upregulates synovial 11HSD1, this upregulation is controlled by TNF-␣ and IL-1 and that the increased supply of local corticosterone might contribute to feedback regulation of inflammation.
Endocrine regulations, 2004
Spontaneously hypertensive rats (SHR) selected from Wistar Kyoto (WKY) strain represent an animal... more Spontaneously hypertensive rats (SHR) selected from Wistar Kyoto (WKY) strain represent an animal model of human essential hypertension. This strain of rats is known by excessive neuroendocrine and cardiovascular responses under stress. The aim of the present study was: 1. To compare the reactivity of hypothalamic-pituitary-adrenocortical axis (HPA) to acute mild stress of handling between SHR and WKY rats, 2. to compare the behavioral activity of both strains under basal conditions and during chronic unpredictable emotional stress. Seven to eight weeks old male SHR and WKY rats bred in the Physiological Institute, Academy of Sciences of the Czech Republic (Prague) were used. Acute stress was induced by 2-minute handling of the animals in their cage. Blood plasma was analyzed for ACTH and corticosterone (CORT) by specific radioimmunoassay. Chronic unpredictable stress lasted 20 days and consisted of random exposures to following interventions: Light on or off for 24 h, overcrowding ...
Life sciences, 1989
The effects of the α 2 adrenergic receptor antagonists yohimbine (YOH) and Idazoxan (ID) on secre... more The effects of the α 2 adrenergic receptor antagonists yohimbine (YOH) and Idazoxan (ID) on secretion of PRL were compared in nonanesthetized male rats bearing permanent intraatrial cannulae for iv drug delivery and serial blood sampling. YOH ...
Life Sciences, Nov 25, 2006
Leptin, a hormone regulating body weight, food intake, and metabolism, is associated with activat... more Leptin, a hormone regulating body weight, food intake, and metabolism, is associated with activation of immune cells and inflammation. In this study we analyzed levels of leptin, adrenocorticotropic hormone (ACTH), corticosterone, interleukin 1beta (IL-1beta), and nitric oxide (NO) production on days 10 and 22 of adjuvant arthritis (AA) in male Long Evans rats to ascertain possible relationship of leptin with its modulators during the early and late phases of chronic inflammation. The circulating leptin levels were significantly reduced already on day 10 of AA compared to controls (1.97+/-0.22 ng/ml vs. 3.08+/-0.25 ng/ml, p&amp;amp;amp;amp;amp;amp;amp;lt;0.05); on day 22 no significant further drop was observed (1.06+/-0.21 ng/ml). Leptin mRNA in epididymal fat tissue was reduced in arthritic animals compared to controls on day 22 (0.61+/-0.09 vs. 1.30+/-0.1 arbU/GAPDH (p&amp;amp;amp;amp;amp;amp;amp;lt;0.01). IL-1beta concentration in spleen was enhanced on day 10 of AA (24.55+/-4.67 pg/100 microg protein vs. 14.33+/-1.71 pg/100 microg protein; p&amp;amp;amp;amp;amp;amp;amp;lt;0.05); on day 22 it did not differ from controls. ACTH and corticosterone levels were significantly elevated only on day 22 of AA (ACTH: 306.17+/-42.22 pg/ml vs. 157.61+/-23.94 pg/ml; p&amp;amp;amp;amp;amp;amp;amp;lt;0.05; corticosterone: 5.24+/-1.38 microg/100 ml vs. 1.05+/-0.23 microg/100 ml; p&amp;amp;amp;amp;amp;amp;amp;lt;0.01). Nitrate levels were enhanced similarly on days 10 (49.86+/-1.83 microM) and 22 of AA (43.58+/-2.17 microM), compared to controls (23.42+/-1.39 microM, p&amp;amp;amp;amp;amp;amp;amp;lt;0.001). These results show that corticosterone does not stimulate leptin production during AA. The suppression of leptin may be a consequence of permanent activation of NO, IL-1beta, and of lower weight gain. Circulating leptin does not seem to play a key role in the progression of chronic arthritis.
Prague medical report, 2014
The aim of the present study was to examine the cross-sensitization induced by prenatal methamphe... more The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA) exposure to adult amphetamine (AMP) treatment in male and female rats. Rat mothers received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male and female offspring (prenatally MA- or saline-exposed) were administered with AMP (5 mg/kg) or saline (1 ml/kg) in adulthood. Behaviour in unknown environment was examined in open field test (Laboras), active drug-seeking behaviour in conditioned place preference test (CPP), spatial memory in the Morris water maze (MWM), and levels of corticosterone (CORT) were analyzed by enzyme immunoassay (EIA). Our data demonstrate that in Laboras test, AMP treatment in adulthood increased general locomotion (time and distance travelled) regardless of the prenatal exposure and sex, while AMP increased exploratory activity (rearing) only in prenatally MA-exposed animals. AMP induced sensitization only in male ra...
Endocrine regulations, 2006
Proinflammatory cytokines IL-1beta, and IL-6 are synthesized in the brain, where they exert local... more Proinflammatory cytokines IL-1beta, and IL-6 are synthesized in the brain, where they exert local regulatory functions. Our aim was to find out whether, along with the activation of hypothalamo-pituitary-adrenocortical (HPA) axis and prolactin (PRL), the acute systemic enhancement of IL-1beta affects its own production in the hypothalamus as well as that of IL-6. Forty five minutes after a single i.p. administration of recombinant rat IL-1beta (5 microg/kg) to male Long Evans rats we estimated the expression of IL-1beta and IL-6 mRNA in the hypothalamus by real time PCR, ACTH, corticosterone (CORT), and PRL by RIA RESULTS: IL-1beta administration stimulated the expression of IL-1beta mRNA in the hypothalamus by 99 %, but not that of IL-6. It also significantly activated plasma levels of ACTH, PRL, CORT, and CORT production in adrenal gland. These results indicate that acute peripheral enhancement of IL-1beta may induce neuroendocrine changes also via the immediate activation of its ...
Cellular and molecular neurobiology, 2001
1. The aim of this study was to compare the effects of acute amphetamine (AMPH) treatment and res... more 1. The aim of this study was to compare the effects of acute amphetamine (AMPH) treatment and restraint stress on plasma level of prolactin (PRL) and PRL mRNA expression in the adenohypophysis in Sprague-Dawley and Lewis male rats, the latter known to have a deficient hypothalamo-pituitary-adrenal (HPA) axis. 2. Both restraint stress and AMPH treatment (i.p. in a dose of 8 mg/kg of b.w.) were applied 15 or 30 min before termination of the experiment. Plasma PRL and corticosterone (CORT) were determined by radioimmunoassay. PRL mRNA expression was estimated by a dot-blot hybridization. 3. Restraint stress and AMPH treatment induced a significant increase in the CORT plasma level, as an indicator of stress response. Compared to Sprague-Dawley rats, the magnitude of CORT increase after both stimuli was significantly lower in Lewis rats. 4. Although restraint stress significantly increased the PRL plasma levels in both rat strains, AMPH treatment reduced the PRL levels in both rat strai...
Rheumatology International, 2008
Anxiety and depression commonly occur in the pathology of rheumatic diseases. Little is known abo... more Anxiety and depression commonly occur in the pathology of rheumatic diseases. Little is known about how inflammatory disease in its early stage, before any clinical manifestation, may affect general activity. The aim of this study was to compare the anxiety-like behaviour in the early stage of adjuvant arthritis (AA), and the paw edema, and corticosterone (CORT) levels in the developed stage of AA among male and female Long Evans rats. The behavioural activity was evaluated by elevated plus maze tests. These revealed significantly reduced number of entries into the open arm of the maze in arthritic males compared to controls or to females 4 days after AA induction. Arthrihtic and control females did not differ. The number of entries into the closed arm of the maze was the same across the genders and studied intervals. Time spent in the open arm was significantly lower in arthritic males against controls or arthitic females. Time spent in the closed arm showed inverse picture to the time spent in the open arm. Hind paw swelling measured on day 23 of AA was the same in males and females, as was the elevation of CORT levels in plasma. Male rats showed anxiety-like behaviour on day 4 of AA, while female rats did not show any change, indicating different brain sensitivity to early inflammation among the genders.
Rheumatology International, 2011
The purpose of this study was to evaluate the effect of β-(1,3/1,6)-D: -glucan isolated from Pleu... more The purpose of this study was to evaluate the effect of β-(1,3/1,6)-D: -glucan isolated from Pleurotus ostreatus (β-glucan-PO) on prophylactic treatment of adjuvant arthritis (AA) with methotrexate (MTX) in rats. Groups of rats with AA were treated with methotrexate (1 mg/kg/week), β-glucan-PO (1 mg/kg every second day) or their combination for the period of 28 days from adjuvant application. Body mass, hind paw swelling, arthrogram scores and a level of serum albumin were measured as markers of inflammation and arthritis. Treatment with low dose of MTX significantly inhibited the markers of both inflammation and arthritis. MTX and its combination with β-glucan-PO significantly increased body mass of arthritic rats. β-glucan-PO administered alone significantly decreased both the hind paw swelling and arthritic score. In combination with MTX, β-glucan-PO markedly potentiated the beneficial effects of MTX, which resulted in a more significant reduction of hind paw swelling and arthritic scores. The concentration of albumin in the serum of arthritic controls was significantly lower than in healthy controls. Both MTX alone and the combination treatment with MTX + β-glucan-PO significantly inhibited the decrease in serum albumin. β-Glucan-PO increased the treatment efficacy of basal treatment of AA with MTX.
Rheumatology International, 2009
Methotrexate (MTX) has been frequently used in the treatment of rheumatoid arthritis (RA). Howeve... more Methotrexate (MTX) has been frequently used in the treatment of rheumatoid arthritis (RA). However, its action on arthritis associated male hypogonadism, or anorexia related low leptin production has not yet been studied. The well-established model of human RA is rat adjuvant-induced arthritis (AA). In the present series we aimed at the evaluation of the effects of MTX on AA induced inflammatory parameters, testosterone suppression, and anorexia associated lowered leptin release. AA was induced in male Lewis rats by intradermal injection of heat killed Mycobacterium butyricum in incomplete Freund&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s adjuvant in the base of the tail. Arthritic rats were treated with two doses of MTX: 0.3 and 0.5 mg/kg twice a week orally for the period of 28 days. The evaluated parameters were body mass, hind-paw swelling, arthrogram scores, serum albumin, total testosterone and leptin on days 14, 21 and 28 of AA. MTX treatment ameliorated all parameters studied dose dependently. Higher dose of MTX induced a significant reduction in the hind-paw swelling, arthritic score, and an increase in serum albumin in all examined time intervals of AA. This dose also significantly improved the suppressed testosterone and leptin levels found in arthritic rats. Prophylactic MTX treatment of rats with AA improved all inflammatory and arthritic parameters studied indicating its clear anti-inflammatory effects. The significant improvement of testosterone and leptin shows beneficial effects of MTX on reproduction and anorexia related leptin reduction during chronic AA.
Neuroscience Letters, 2011
We studied anxiety-like behavior in the elevated plus-maze (EPM) tests in male Lewis rats on days... more We studied anxiety-like behavior in the elevated plus-maze (EPM) tests in male Lewis rats on days 2 and 4 of adjuvant arthritis (AA). In plasma we analyzed C-reactive protein (CRP), albumin, ACTH, corticosterone, in the hippocampus the mRNA expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), corticotrophin releasing factor (CRH), NADPH oxidases NOX1 and NOX2, and inducible NO-synthase (iNOS). EPM tests showed a higher anxiety index in AA rats on days 2 and 4 and reduction of total entries. On days 2 and 4 we found reduced plasma albumin, enhanced CRP, ACTH and corticosterone, and in the hippocampus enhanced mRNA for NOX1 and IL-1β in AA rats, on day 4 we found enhanced mRNAs for iNOS and IL-6, and reduced mRNA for CRH. The mRNA for NOX2 did not change on any experimental day. These results suggest enhanced anxiety, as well as locomotor impairment during the early phase of AA that correlate with enhanced mRNA expressions of parameters of oxidative stress NOX1, iNOS, and inflammatory cytokines IL-1β and IL-6 in the hippocampus.
Neonatology, 1986
The role of endogenous thyrotropin-releasing hormone (TRH) in the control of pituitary thyroid-st... more The role of endogenous thyrotropin-releasing hormone (TRH) in the control of pituitary thyroid-stimulating hormone (TSH) and growth hormone (GH) secretion was studied during postnatal maturation in female Wistar rats. Half of the sucklings in each litter was treated intraperitoneally with either specific rabbit antiserum against TRH or normal rabbit serum (0.1-0.3 ml according to age). All animals were decapitated after 2 h. The presence of anti-TRH activity was checked as a binding of labelled TRH with plasma of the experimental animals. Immunoneutralization of endogenous TRH resulted in a decrease of plasma TSH in 3- to 15-day-old female pups as compared to control littermates. No effect of TRH antibody injection was seen at the ages of 1, 21, 30 and 70 days despite the presence of excess antibody in the plasma. A profound effect of TRH antibody on plasma TSH was seen again at the age of 100 days. Plasma GH in the same animals exhibited a paradoxical increase after TRH immunoneutralization at the age of 5 and 8 days, a decrease was found at the age of 21 days. It was concluded that hypothalamic TRH control of TSH secretion matures early in Wistar rats. Hypothalamic secretion of TRH at the ages of 1, 21, 30, and 70 days is low and(or) its role in TSH regulation is masked by other regulating factors. TRH may play a dual role in the regulation of GH secretion during the postnatal period.
Behavioural Brain Research, 2003
SUMMARY 1. The aim of this study was to compare the effects of acute amphetamine (AMPH) treatment... more SUMMARY 1. The aim of this study was to compare the effects of acute amphetamine (AMPH) treatment and restraint stress on plasma level of prolactin (PRL) and PRL mRNA expression in the adenohypophysis in Sprague-Dawley and Lewis male rats, the latter known to have a deficient hypothalamo-pituitary-adrenal (HPA) axis. 2. Both restraint stress and AMPH treatment (i.p. in a dose of 8 mg/kg of b.w.) were applied 15 or 30 min before termination of the experiment. Plasma PRL and corticosterone (CORT) were determined by radioimmunoassay. PRL mRNA expression was estimated by a dot-blot hybridization. 3. Restraint stress and AMPH treatment induced a significant increase in the CORT plasma level, as an indicator of stress response. Compared to Sprague-Dawley rats, the magnitude of CORT increase after both stimuli was significantly lower in Lewis rats. 4. Although restraint stress significantly increased the PRL plasma levels in both rat strains, AMPH treatment reduced the PRL levels in both r...
Endocrine regulations, 2006
OBJECTIVE Proinflammatory cytokines IL-1beta, and IL-6 are synthesized in the brain, where they e... more OBJECTIVE Proinflammatory cytokines IL-1beta, and IL-6 are synthesized in the brain, where they exert local regulatory functions. Our aim was to find out whether, along with the activation of hypothalamo-pituitary-adrenocortical (HPA) axis and prolactin (PRL), the acute systemic enhancement of IL-1beta affects its own production in the hypothalamus as well as that of IL-6. METHOD Forty five minutes after a single i.p. administration of recombinant rat IL-1beta (5 microg/kg) to male Long Evans rats we estimated the expression of IL-1beta and IL-6 mRNA in the hypothalamus by real time PCR, ACTH, corticosterone (CORT), and PRL by RIA RESULTS: IL-1beta administration stimulated the expression of IL-1beta mRNA in the hypothalamus by 99 %, but not that of IL-6. It also significantly activated plasma levels of ACTH, PRL, CORT, and CORT production in adrenal gland. CONCLUSION These results indicate that acute peripheral enhancement of IL-1beta may induce neuroendocrine changes also via the ...
Journal of Cachexia, Sarcopenia and Muscle
Background: Sarcopenia is defined as loss of skeletal muscle mass and function. In clinical resea... more Background: Sarcopenia is defined as loss of skeletal muscle mass and function. In clinical research, measurement of skeletal muscle mass index (SMI) is based on appendicular skeletal muscle mass (kg)/height 2 (m 2) <2 SD below the mean of a young reference group. 1 SMI was found to be associated with increased physical disability independent of age, ethnicity, comorbidity, and fat mass. 2 Alternatively, SMI is reported as weight-adjusted SMI derived from values obtained from bioelectrical impedance analysis. 3 A recent study suggests the height-adjusted SMI has better correlation with reduced muscle strength and gait speed. 4 Methods: We assessed data on 2521 women with a variety of medical conditions who presented to a tertiary hospital for assessment of bone mineral density (BMD). Some of these women also had concurrent body composition and anthropometry performed. Aims: We aim (i) To determine the relationship between BMD, body composition, and anthropometry in the whole group and subgroups. (ii) To determine The relationship between age and decline in skeletal muscle mass and its relationship to anthropometric variables. (iii) To explore leg length (which appears constant with age) vs. height (which declines with age) in standardizing skeletal muscle measurement for body size. Results: Participants were females aged 40-97 years (mean 59 years). The majority of the patients who were referred presented on a background of breast cancer (n = 679, 27.9%), followed by screening or other causes (n = 563, 22.3%) and steroid use (n = 241, 9.6%). When analysed on regression variable plots, reduction in sitting height, biceps, thigh skin fold, total body, femoral neck BMD, and T score occurs with age. Discussion: There were no changes observed in leg length with age. This suggests that leg length may be used as an alternative to height in the calculation of skeletal muscle mass index.
Neuroimmunomodulation, 2004
Several interleukins (ILs) including IL-1 beta and IL-6 are produced in the anterior pituitary (A... more Several interleukins (ILs) including IL-1 beta and IL-6 are produced in the anterior pituitary (AP) where they probably participate in the local regulation of hormone production. Immune challenge brings about the dysregulation of immune-endocrine interaction and enhanced the expression of pituitary IL-1 beta and IL-6. Little is known about regulation of their production, and therefore the purpose of the present work was to describe the relationship between circulating corticosterone and the mRNA expression of proopiomelanocortin (POMC), IL-1 beta and IL-6 in the AP during a 24-hour cycle in normal rats and rats with acute adjuvant arthritis (AA). Groups of intact male Long-Evans rats and rats 23 days after induction of AA kept on a 12-hour light/dark cycle (light on at 6:00 a.m.) were killed at 4-hour intervals starting at 2:00 p.m. Trunk blood was used for corticosterone determination by radioimmunoassay. Adenopituitaries were extracted for total RNA and the message of interest was quantitated by real-time PCR using specific primers and TaqMan probes. Parameters of rhythms were evaluated by cosinor analysis. In normal rats, serum corticosterone showed a circadian rhythm with the peak at 6:00 p.m. and the nadir in the morning hours (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). POMC mRNA in AP also showed a circadian rhythm (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) which was inversely related to corticosterone levels. IL-1beta and IL-6 expression in normal rats showed clear-cut daily rhythms (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) with the nadirs in the dark period, in contrast to the corticosterone peak in plasma. In arthritic rats, rhythmic corticosterone secretion was suppressed with a plateau pattern of the rhythm. The mean POMC expression was higher than in controls, and the rhythm failed to be significant. IL-1 beta expression was suppressed by AA (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) but the rhythm was still present (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). The rhythmic pattern of IL-6 expression was similar to that of controls, but with higher mesor values (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). These results suggest a regulatory relationship between circulating corticosterone and the expression of POMC, IL-1 beta and IL-6 in AP of normal rats. Arthritis induced a higher expression of POMC and IL-6 in the AP and a suppression of IL-1 beta mRNA during the 24-hour cycle which suggests the involvement of different regulatory mechanisms compared to normal conditions.
Brain Research Bulletin, 1989
We studied the effects of adjuvant arthritis (AA) on the endocrine circadian rhythms of plasma pr... more We studied the effects of adjuvant arthritis (AA) on the endocrine circadian rhythms of plasma prolactin (PRL), growth hormone (GH), insulin-like growth factor-1 (IGF-1), luteinizing hormone (LH), testosterone, and melatonin and of pituitary PRL and GH mRNA in male Long Evans rats. Groups of control and AA rats (studied 23 days after AA induction) that were housed under a 12/12 h light/dark cycle (light on at 06:00 h) were killed at 4 h intervals starting at 14:00 h. Cosinor analysis revealed a significant 12 h rhythm in PRL and PRL mRNA (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) in controls with peaks at 14:00 h and 02:00 h, respectively. The peak at 02:00 h was abolished in the AA group resulting in a significant 24 h rhythm in parallel with that of PRL (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) and PRL mRNA (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Growth hormone showed no rhythm, but a significant rhythm of GH mRNA was present in both groups (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Insulin-like growth factor-1 showed a 24 h rhythm in control but not in AA rats. The mean values of GH, GH mRNA, and IGF-1 were significantly reduced in AA. Luteinizing hormone displayed a significant 24 h rhythm (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) peaking in the dark period in the control but not AA group. Testosterone showed in phase temporal changes of LH levels with AA abolishing the 02:00 h peak. Melatonin exhibited a significant 24 h rhythm in control (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and AA (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) rats with maximum levels during the dark phase; the mesor value was higher in the AA males. These results demonstrate that AA interferes with the rhythms of all the studied hormones except the non-24 h (arrhythmic) GH secretion pattern and the rhythm in melatonin. The persistence of a distinct melatonin rhythm in AA suggests the observed disturbances of hormonal rhythms in this condition do not occur at the level of the pineal gland.
Molecular and Cellular Endocrinology, Mar 1, 2010
11-Hydroxysteroid dehydrogenase 1 (11HSD1) regulates local glucocorticoid activity and plays an ... more 11-Hydroxysteroid dehydrogenase 1 (11HSD1) regulates local glucocorticoid activity and plays an important role in various diseases. Here, we studied whether arthritis modulates 11HSD1, what is the role of pro-inflammatory cytokines in this process and whether altered local metabolism of glucocorticoids may contribute to the feedback regulation of inflammation. Adjuvant arthritis increased synovial 11HSD1 mRNA and 11-reductase activity but treatments with tumor necrosis factor ␣ (TNF-␣) and interleukin 1 (IL-1) antagonists etanercept and anakinra reduced 11HSD1 upregulation. Treatment with carbenoxolone, an 11HSD inhibitor, increased expression of TNF-␣, cyclooxygenase 2, and osteopontin mRNA without any changes in the plasma levels of corticosterone. Similar changes were observed when arthritic rats were treated with RU486, an antagonist of GR. This study suggests that arthritis upregulates synovial 11HSD1, this upregulation is controlled by TNF-␣ and IL-1 and that the increased supply of local corticosterone might contribute to feedback regulation of inflammation.
Endocrine regulations, 2004
Spontaneously hypertensive rats (SHR) selected from Wistar Kyoto (WKY) strain represent an animal... more Spontaneously hypertensive rats (SHR) selected from Wistar Kyoto (WKY) strain represent an animal model of human essential hypertension. This strain of rats is known by excessive neuroendocrine and cardiovascular responses under stress. The aim of the present study was: 1. To compare the reactivity of hypothalamic-pituitary-adrenocortical axis (HPA) to acute mild stress of handling between SHR and WKY rats, 2. to compare the behavioral activity of both strains under basal conditions and during chronic unpredictable emotional stress. Seven to eight weeks old male SHR and WKY rats bred in the Physiological Institute, Academy of Sciences of the Czech Republic (Prague) were used. Acute stress was induced by 2-minute handling of the animals in their cage. Blood plasma was analyzed for ACTH and corticosterone (CORT) by specific radioimmunoassay. Chronic unpredictable stress lasted 20 days and consisted of random exposures to following interventions: Light on or off for 24 h, overcrowding ...
Life sciences, 1989
The effects of the α 2 adrenergic receptor antagonists yohimbine (YOH) and Idazoxan (ID) on secre... more The effects of the α 2 adrenergic receptor antagonists yohimbine (YOH) and Idazoxan (ID) on secretion of PRL were compared in nonanesthetized male rats bearing permanent intraatrial cannulae for iv drug delivery and serial blood sampling. YOH ...
Life Sciences, Nov 25, 2006
Leptin, a hormone regulating body weight, food intake, and metabolism, is associated with activat... more Leptin, a hormone regulating body weight, food intake, and metabolism, is associated with activation of immune cells and inflammation. In this study we analyzed levels of leptin, adrenocorticotropic hormone (ACTH), corticosterone, interleukin 1beta (IL-1beta), and nitric oxide (NO) production on days 10 and 22 of adjuvant arthritis (AA) in male Long Evans rats to ascertain possible relationship of leptin with its modulators during the early and late phases of chronic inflammation. The circulating leptin levels were significantly reduced already on day 10 of AA compared to controls (1.97+/-0.22 ng/ml vs. 3.08+/-0.25 ng/ml, p&amp;amp;amp;amp;amp;amp;amp;lt;0.05); on day 22 no significant further drop was observed (1.06+/-0.21 ng/ml). Leptin mRNA in epididymal fat tissue was reduced in arthritic animals compared to controls on day 22 (0.61+/-0.09 vs. 1.30+/-0.1 arbU/GAPDH (p&amp;amp;amp;amp;amp;amp;amp;lt;0.01). IL-1beta concentration in spleen was enhanced on day 10 of AA (24.55+/-4.67 pg/100 microg protein vs. 14.33+/-1.71 pg/100 microg protein; p&amp;amp;amp;amp;amp;amp;amp;lt;0.05); on day 22 it did not differ from controls. ACTH and corticosterone levels were significantly elevated only on day 22 of AA (ACTH: 306.17+/-42.22 pg/ml vs. 157.61+/-23.94 pg/ml; p&amp;amp;amp;amp;amp;amp;amp;lt;0.05; corticosterone: 5.24+/-1.38 microg/100 ml vs. 1.05+/-0.23 microg/100 ml; p&amp;amp;amp;amp;amp;amp;amp;lt;0.01). Nitrate levels were enhanced similarly on days 10 (49.86+/-1.83 microM) and 22 of AA (43.58+/-2.17 microM), compared to controls (23.42+/-1.39 microM, p&amp;amp;amp;amp;amp;amp;amp;lt;0.001). These results show that corticosterone does not stimulate leptin production during AA. The suppression of leptin may be a consequence of permanent activation of NO, IL-1beta, and of lower weight gain. Circulating leptin does not seem to play a key role in the progression of chronic arthritis.
Prague medical report, 2014
The aim of the present study was to examine the cross-sensitization induced by prenatal methamphe... more The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA) exposure to adult amphetamine (AMP) treatment in male and female rats. Rat mothers received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male and female offspring (prenatally MA- or saline-exposed) were administered with AMP (5 mg/kg) or saline (1 ml/kg) in adulthood. Behaviour in unknown environment was examined in open field test (Laboras), active drug-seeking behaviour in conditioned place preference test (CPP), spatial memory in the Morris water maze (MWM), and levels of corticosterone (CORT) were analyzed by enzyme immunoassay (EIA). Our data demonstrate that in Laboras test, AMP treatment in adulthood increased general locomotion (time and distance travelled) regardless of the prenatal exposure and sex, while AMP increased exploratory activity (rearing) only in prenatally MA-exposed animals. AMP induced sensitization only in male ra...
Endocrine regulations, 2006
Proinflammatory cytokines IL-1beta, and IL-6 are synthesized in the brain, where they exert local... more Proinflammatory cytokines IL-1beta, and IL-6 are synthesized in the brain, where they exert local regulatory functions. Our aim was to find out whether, along with the activation of hypothalamo-pituitary-adrenocortical (HPA) axis and prolactin (PRL), the acute systemic enhancement of IL-1beta affects its own production in the hypothalamus as well as that of IL-6. Forty five minutes after a single i.p. administration of recombinant rat IL-1beta (5 microg/kg) to male Long Evans rats we estimated the expression of IL-1beta and IL-6 mRNA in the hypothalamus by real time PCR, ACTH, corticosterone (CORT), and PRL by RIA RESULTS: IL-1beta administration stimulated the expression of IL-1beta mRNA in the hypothalamus by 99 %, but not that of IL-6. It also significantly activated plasma levels of ACTH, PRL, CORT, and CORT production in adrenal gland. These results indicate that acute peripheral enhancement of IL-1beta may induce neuroendocrine changes also via the immediate activation of its ...
Cellular and molecular neurobiology, 2001
1. The aim of this study was to compare the effects of acute amphetamine (AMPH) treatment and res... more 1. The aim of this study was to compare the effects of acute amphetamine (AMPH) treatment and restraint stress on plasma level of prolactin (PRL) and PRL mRNA expression in the adenohypophysis in Sprague-Dawley and Lewis male rats, the latter known to have a deficient hypothalamo-pituitary-adrenal (HPA) axis. 2. Both restraint stress and AMPH treatment (i.p. in a dose of 8 mg/kg of b.w.) were applied 15 or 30 min before termination of the experiment. Plasma PRL and corticosterone (CORT) were determined by radioimmunoassay. PRL mRNA expression was estimated by a dot-blot hybridization. 3. Restraint stress and AMPH treatment induced a significant increase in the CORT plasma level, as an indicator of stress response. Compared to Sprague-Dawley rats, the magnitude of CORT increase after both stimuli was significantly lower in Lewis rats. 4. Although restraint stress significantly increased the PRL plasma levels in both rat strains, AMPH treatment reduced the PRL levels in both rat strai...
Rheumatology International, 2008
Anxiety and depression commonly occur in the pathology of rheumatic diseases. Little is known abo... more Anxiety and depression commonly occur in the pathology of rheumatic diseases. Little is known about how inflammatory disease in its early stage, before any clinical manifestation, may affect general activity. The aim of this study was to compare the anxiety-like behaviour in the early stage of adjuvant arthritis (AA), and the paw edema, and corticosterone (CORT) levels in the developed stage of AA among male and female Long Evans rats. The behavioural activity was evaluated by elevated plus maze tests. These revealed significantly reduced number of entries into the open arm of the maze in arthritic males compared to controls or to females 4 days after AA induction. Arthrihtic and control females did not differ. The number of entries into the closed arm of the maze was the same across the genders and studied intervals. Time spent in the open arm was significantly lower in arthritic males against controls or arthitic females. Time spent in the closed arm showed inverse picture to the time spent in the open arm. Hind paw swelling measured on day 23 of AA was the same in males and females, as was the elevation of CORT levels in plasma. Male rats showed anxiety-like behaviour on day 4 of AA, while female rats did not show any change, indicating different brain sensitivity to early inflammation among the genders.
Rheumatology International, 2011
The purpose of this study was to evaluate the effect of β-(1,3/1,6)-D: -glucan isolated from Pleu... more The purpose of this study was to evaluate the effect of β-(1,3/1,6)-D: -glucan isolated from Pleurotus ostreatus (β-glucan-PO) on prophylactic treatment of adjuvant arthritis (AA) with methotrexate (MTX) in rats. Groups of rats with AA were treated with methotrexate (1 mg/kg/week), β-glucan-PO (1 mg/kg every second day) or their combination for the period of 28 days from adjuvant application. Body mass, hind paw swelling, arthrogram scores and a level of serum albumin were measured as markers of inflammation and arthritis. Treatment with low dose of MTX significantly inhibited the markers of both inflammation and arthritis. MTX and its combination with β-glucan-PO significantly increased body mass of arthritic rats. β-glucan-PO administered alone significantly decreased both the hind paw swelling and arthritic score. In combination with MTX, β-glucan-PO markedly potentiated the beneficial effects of MTX, which resulted in a more significant reduction of hind paw swelling and arthritic scores. The concentration of albumin in the serum of arthritic controls was significantly lower than in healthy controls. Both MTX alone and the combination treatment with MTX + β-glucan-PO significantly inhibited the decrease in serum albumin. β-Glucan-PO increased the treatment efficacy of basal treatment of AA with MTX.
Rheumatology International, 2009
Methotrexate (MTX) has been frequently used in the treatment of rheumatoid arthritis (RA). Howeve... more Methotrexate (MTX) has been frequently used in the treatment of rheumatoid arthritis (RA). However, its action on arthritis associated male hypogonadism, or anorexia related low leptin production has not yet been studied. The well-established model of human RA is rat adjuvant-induced arthritis (AA). In the present series we aimed at the evaluation of the effects of MTX on AA induced inflammatory parameters, testosterone suppression, and anorexia associated lowered leptin release. AA was induced in male Lewis rats by intradermal injection of heat killed Mycobacterium butyricum in incomplete Freund&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s adjuvant in the base of the tail. Arthritic rats were treated with two doses of MTX: 0.3 and 0.5 mg/kg twice a week orally for the period of 28 days. The evaluated parameters were body mass, hind-paw swelling, arthrogram scores, serum albumin, total testosterone and leptin on days 14, 21 and 28 of AA. MTX treatment ameliorated all parameters studied dose dependently. Higher dose of MTX induced a significant reduction in the hind-paw swelling, arthritic score, and an increase in serum albumin in all examined time intervals of AA. This dose also significantly improved the suppressed testosterone and leptin levels found in arthritic rats. Prophylactic MTX treatment of rats with AA improved all inflammatory and arthritic parameters studied indicating its clear anti-inflammatory effects. The significant improvement of testosterone and leptin shows beneficial effects of MTX on reproduction and anorexia related leptin reduction during chronic AA.
Neuroscience Letters, 2011
We studied anxiety-like behavior in the elevated plus-maze (EPM) tests in male Lewis rats on days... more We studied anxiety-like behavior in the elevated plus-maze (EPM) tests in male Lewis rats on days 2 and 4 of adjuvant arthritis (AA). In plasma we analyzed C-reactive protein (CRP), albumin, ACTH, corticosterone, in the hippocampus the mRNA expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), corticotrophin releasing factor (CRH), NADPH oxidases NOX1 and NOX2, and inducible NO-synthase (iNOS). EPM tests showed a higher anxiety index in AA rats on days 2 and 4 and reduction of total entries. On days 2 and 4 we found reduced plasma albumin, enhanced CRP, ACTH and corticosterone, and in the hippocampus enhanced mRNA for NOX1 and IL-1β in AA rats, on day 4 we found enhanced mRNAs for iNOS and IL-6, and reduced mRNA for CRH. The mRNA for NOX2 did not change on any experimental day. These results suggest enhanced anxiety, as well as locomotor impairment during the early phase of AA that correlate with enhanced mRNA expressions of parameters of oxidative stress NOX1, iNOS, and inflammatory cytokines IL-1β and IL-6 in the hippocampus.
Neonatology, 1986
The role of endogenous thyrotropin-releasing hormone (TRH) in the control of pituitary thyroid-st... more The role of endogenous thyrotropin-releasing hormone (TRH) in the control of pituitary thyroid-stimulating hormone (TSH) and growth hormone (GH) secretion was studied during postnatal maturation in female Wistar rats. Half of the sucklings in each litter was treated intraperitoneally with either specific rabbit antiserum against TRH or normal rabbit serum (0.1-0.3 ml according to age). All animals were decapitated after 2 h. The presence of anti-TRH activity was checked as a binding of labelled TRH with plasma of the experimental animals. Immunoneutralization of endogenous TRH resulted in a decrease of plasma TSH in 3- to 15-day-old female pups as compared to control littermates. No effect of TRH antibody injection was seen at the ages of 1, 21, 30 and 70 days despite the presence of excess antibody in the plasma. A profound effect of TRH antibody on plasma TSH was seen again at the age of 100 days. Plasma GH in the same animals exhibited a paradoxical increase after TRH immunoneutralization at the age of 5 and 8 days, a decrease was found at the age of 21 days. It was concluded that hypothalamic TRH control of TSH secretion matures early in Wistar rats. Hypothalamic secretion of TRH at the ages of 1, 21, 30, and 70 days is low and(or) its role in TSH regulation is masked by other regulating factors. TRH may play a dual role in the regulation of GH secretion during the postnatal period.