Basal Values (basal + value)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Expression of Endothelial Cell Adhesion Molecules in Neovascularized Tissue

MICROCIRCULATION, Issue 4 2000
GINA VALLIEN
ABSTRACT Objective: Recent studies indicate that endothelial cells of newly formed blood vessels are activated and exhibit a distinct phenotype that may influence the responses of these microvessels to an inflammatory stimulus. The objective of this study was to compare the basal and cytokine-stimulated expression of endothelial cell adhesion molecules in neovascularized tissue to normal (nonproliferating) vascular beds. Methods: The expression of P- and E-selectin, VCAM-1, ICAM-1, ICAM-2, and PECAM-1 was measured, using the dual radiolabeled mAb technique, in subcutaneously implanted (for 10,15 days) polyurethane sponges, skin, heart, lung, and intestine of male C57BL/6 mice (background). Results: Basal values of PECAM-1 and ICAM-2 revealed a low vascular density in the implanted sponge matrices that is comparable to skin. When normalized for vascular surface area (PECAM-1 or ICAM-1 expression), the basal level of E- and P-selectin expression was highest in neovascularized sponge and skin. TNF-, elicited an increased expression of all endothelial CAMs, except PECAM-1 and ICAM-2, but the responses were blunted in sponge and skin, relative to other vascular beds. Conclusions: These findings indicate that endothelial cells in newly formed blood vessels exhibit a pattern of basal and cytokine-induced expression of certain adhesion glycoproteins that is similar to nonproliferating cutaneous vessels. [source]


Influence of deoxynivalenol on the D -glucose transport across the isolated epithelium of different intestinal segments of laying hens

JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 5-6 2007
W. A. Awad
Summary Deoxynivalenol (DON) decreases glucose absorption in the proximal jejunum of laying hens in vitro and this effect is apparently mediated by the inhibition of the sodium d -glucose co-transporter. DON could modulate the sugar transport of other intestinal regions of chickens. For this purpose, we have measured the effects of DON on the Na+d -glucose co-transporter, by addition of DON after and before a glucose addition in the isolated epithelium from chicken duodenum, jejunum, ileum, caecum and colon by using the Ussing chamber technique in the voltage clamp technique. The data showed in all segments of the gut that the addition of d -glucose on the mucosal side produced an increase in the current (Isc) compared with the basal values, the Isc after glucose addition to the small intestine was greater than the Isc of the large intestine compared with the basal values, specially of the jejunum (p < 0.002), indicating that the jejunum is the segment that is the best prepared for Na+ - d -glucose co-transport. Further addition of 10 ,g DON/ml to the mucosal solution decreased the Isc in all segments and the Isc returned to the basal value, especially in the duodenum and mid jejunum (p < 0.05). In contrast, the addition of 5 mmol d -glucose/l on the mucosal side after incubation of the tissues with DON in all segments had no effect on the Isc (p > 0.05), suggesting that DON previously inhibited the Na+d -glucose co-transport. The blocking effects of DON in duodenum and jejunum were greater than the other regions of the gut. It can be concluded that the small intestine of laying hens has the most relevant role in the carrier mediated glucose transport and the large intestine, having non-significant capacity to transport sugars, appears to offer a minor contribution to glucose transport because the surface area is small. The effect of d -glucose on the Isc was reversed by DON in all segments, especially in the duodenum and jejunum, suggesting that DON entirely inhibited Na+ - d -glucose co-transport. This finding indicates that the inhibition of Na+ co-transport system in all segments could be an important mode of action for DON toxicity of hens. Zusammenfassung Deoxynivalenol (DON) erniedrigt in vitro die Glukoseabsorption im proximalen Jejunum von Legehennen. Dieser Effekt ist vermutlich durch eine Hemmung des Natrium- d -Glukose-Cotransportsystems bedingt. DON könnte außerdem den Glukosetransport in anderen Segmenten des Darms beeinflußen. Zu diesem Zweck haben wir Wirkungen von DON auf das Natrium- d -Glukose-Cotransportsystem gemessen, indem wir DON nach und vor einer Glukosezugabe auf isolierte Darmepithelien des Duodenums, Jejunums, Ileums, Caecums und des Kolons mittels der Ussing-Kammer-Technik in der Volt-Klemmtechnik einwirken ließen. Die erzielten Daten wiesen in allen Segmenten des Darms verglichen mit den Basalwerten einen Anstieg im Strom (Isc) auf, wobei die Isc des Dünndarms bei Glukosegabe signifikant größer als die des Dickdarms waren, was darauf hinweist, dass das Jejunum am besten für den Glukosetransport geeignet war. Eine DON-Zugabe von 10 ,g/ml zur mukosalen Lösung schwächte den Isc in allen Segmenten, wobei die Isc speziell im Duodenum und mittleren Jejunum zum Ausgangswert zurück kehrten. Im Gegensatz dazu brachte die mukosale Glukosezugabe nach der DON-Inkubation keinen signifikanten Anstieg der Isc (p > 0,05), was auf eine durch DON hervorgerufene Blockade des Natrium- d -Glukose-Cotransportsystems schließen ließ. Es kann daraus geschlossen werden, dass der Dünndarm von Legehennen den bedeutendsten Einfluß im Glukosetransportmechanismus nimmt und der Dickdarm aufgrund einer kleineren Oberfläche einen geringeren Beitrag zum Glukosetransport leistet. Dem Isc steigernden Effekt der Glukose konnte signifikant durch DON in den Darmsegmenten besonders im Duodenum und im Jejunum entgegen gewirkt werden, was auf eine umfassende Hemmung des Natrium- d -Glukose-Cotransportsystems hinweist. Die Resultate weisen darauf hin, dass eine Hemmung des Natrium- d -Glukose-Cotransportsystems in allen Darmsegmenten eine wichtige Rolle in der DON-Toxizität für die Henne darstellen könnte. [source]


LDL-apheresis up-regulates VEGF and IGF-I in patients with ischemic limb

JOURNAL OF CLINICAL APHERESIS, Issue 3 2003
Shuzo Kobayashi
Abstract Although it is known that LDL-apheresis improves ischemic limb seen in patients with peripheral arterial occlusive disease (PAOD), the underlying mechanism(s) still remains unknown. We studied whether vascular endothelial growth factor (VEGF) and/or insulin-like growth factor-I (IGF-I) levels correlated with improvement of ischemic limbs after LDL-apheresis. Sixteen patients with PAOD (13 men, 3 women) were enrolled in our study. LDL-apheresis was performed 10 times (treated plasma 3,000 ml) for 5 weeks. Serum level of VEGF significantly increased from 262 ± 171 pg/ml to 306 ± 165 pg/ml before and after LDL-apheresis (P < 0.05). This value further increased up to 441 ± 175 pg/ml 3 months after the end of this therapy (P < 0.01, compared with the basal value and P < 0.05, compared with the value at the end of 10-times session). Increased levels of VEGF paralleled increases in the ankle-brachial pressure index (ABI). After 10-times therapy, IGF-I significantly decreased (P < 0.05), but increased over the basal value 3 months after this therapy. Plasma fibrinogen statistically decreased and remained low for 3 months. The favorable effects of LDL-apheresis may be ascribed to up-regulation of VEGF and IGF-I associated with decreased fibrinogen levels. J. Clin. Apheresis, 18:115,119, 2003. © 2003 Wiley-Liss, Inc. [source]


Surgical closure of patent ductus arteriosus reduces the cerebral tissue oxygenation index in preterm infants: a near-infrared spectroscopy and Doppler study

PEDIATRICS INTERNATIONAL, Issue 3 2006
PATRIZIA ZARAMELLA
Abstract Background: The aim of this study was to investigate the effects of patent ductus arteriosus (PDA) ligature on cerebral oxygen saturation, cerebral blood volume (CBV) and cerebral blood flow velocity by means of near-infrared spectroscopy (NIRS) and transcranial Doppler simultaneous examinations. Methods: This is an observational study considering 16 babies of gestational age 24,34 weeks diagnosed with PDA who underwent surgical ligation. The cerebral oxygen saturation, CBV and blood gases values were obtained 35 min before ligation, so also around the 14th and 27th min after the clip's insertion. Results: Cerebral oxygen saturation, measured as tissue oxygenation index (TOI), decreased significantly after PDA ligation from a basal value of 61.1 (3.8) before surgery to 56.6 (3.3) and 55.8 (2.6)%, for the 14th and 27th min, respectively (P < 0.04). CBV before and after clipping was unvaried. A negative correlation was found between ,pH and ,CBV after ligation (R = 0.52, P = 0.03), whilst a positive correlation was found between ,CBV and ,PaCO2 (R = 0.62, P = 0.009). pH increased at the 27th min post-ligation. Conclusions: NIRS is a tool for obtaining information on cerebral oxygen saturation and CBV changes during surgical PDA ligation at the bedside. A fall in TOI suggests an increased oxygen extraction during PDA surgery. The lack of increase in ,CBV or in diastolic flow velocity show that the PDA before the clipping did not limit cerebral blood flow, the drop in TOI suggests increased oxygen consumption over the clip and the need for accurate monitoring of oxygen utilization after the surgical treatment. [source]


Antioxidants and narrow band-UVB in the treatment of vitiligo: a double-blind placebo controlled trial

CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 6 2007
M. L. Dell'Anna
Summary Background., Vitiligo is an acquired depigmenting disease with uncertain aetiopathogenesis, possibly associated with oxidative stress. Narrowband ultraviolet B phototherapy (NB-UVB) is the most widely used and effective treatment. Aim., To evaluate the clinical effectiveness of NB-UVB and the repairing of oxidative stress-induced damage, using oral supplementation with an antioxidant pool (AP). Methods., Patients (n = 35) with nonsegmental vitiligo were enrolled in a randomized, double-blind, placebo-controlled multicentre trial. The treatment group received, for 2 months before and for 6 months during the NB-UVB treatment, a balanced AP containing ,-lipoic acid, vitamins C and E, and polyunsaturated fatty acids. The area and number of lesions, as well as some parameters of the oxidation,reduction (redox) status of the peripheral blood mononuclear cells (PBMCs) were estimated at the beginning, after 2 months, and at the end of the trial. Results., In total, 28 patients completed the study. After 2 months of AP supplementation, the catalase activity and the production of reactive oxygen species (ROS) were 121% and 57% of the basal values (P < 0.05 and P < 0.02 vs. placebo, respectively). The AP increased the therapeutic success of NB-UVB, with 47% of the patients obtaining >,75% repigmentation vs. 18% in the placebo group (P < 0.05). An increase in catalase activity to 114% (P < 0.05 vs. placebo) and decrease in ROS level of up to 60% (P < 0.02 vs. placebo) of the basal value was observed in PBMCs. Finally, the AP intake maintained the membrane lipid ratio (saturated : unsaturated fatty acids 1.8 : 3.1; P < 0.05), counteracting phototherapy-induced saturation. Conclusions., Oral supplementation with AP containing ,-lipoic acid before and during NB-UVB significantly improves the clinical effectiveness of NB-UVB, reducing vitiligo-associated oxidative stress. [source]


RAPID EFFECT OF PROGESTERONE ON TRANSEPITHELIAL RESISTANCE OF HUMAN FETAL MEMBRANES: EVIDENCE FOR NON-GENOMIC ACTION

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 2 2008
CH Verikouki
SUMMARY 1The factors that regulate human fetal membrane transport mechanisms are unknown. The aim of the present study was to investigate the effect of progesterone on transepithelial electrical resistance (RTE) in the human amniochorion. 2Fetal membranes from uncomplicated term pregnancies were obtained immediately after vaginal or Caesarean deliveries. Intact pieces were mounted as planar sheets separating an Ussing chamber. Progesterone (10,4 to 10,7 mol/L), mifepristone (10,4 to 10,8 mol/L) and combinations of progesterone plus mifepristone were applied to the chambers facing the fetal or maternal sides of the membrane. The RTE was measured before and 1, 5, 10, 15, 20, 25, 30, 45 and 60 min after each solution was added (at 37°C). The RTE was calculated in ,.cm2, according to Ohm's law. 3The mean (±SEM) basal value of RTE before the application of any substance in all experiments was 29.1 ± 0.4 ,.cm2., The net change in the RTE (,RTE) in relation to the basal value was calculated in each experiment. Progesterone, mifepristone and the combination of progesterone and mifepristone induced a rapid, surge-type increase in RTE during the 1st min on both sides of the membrane. The combination of progesterone plus mifepristone exerted a synergistic action. The effect was stronger on the fetal side than on the maternal side for all substances tested (P < 0.05). The highest ,RTE during the 1st min on the fetal side was seen with the combination of progesterone plus mifepristone (4.0 ± 0.3 ,.cm2) and the lowest ,RTE occurred with mifepristone (1.5 ± 0.1 ,.cm2). 4The present results demonstrated that the RTE of human fetal membranes increases rapidly in response to progesterone. It is possible that changes in RTE play a role in the control of membrane permeability during pregnancy. [source]


GABA selectively controls the secretory activity of oxytocin neurons in the rat supraoptic nucleus

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2004
Mario Engelmann
Abstract Recently we reported that a single social defeat experience triggers the release of oxytocin (OXT) from somata and dendrites, but not axon terminals, of neurons of the hypothalamic,neurohypophysial system. To further investigate the regulatory mechanisms underlying this dissociated release, we exposed male Wistar rats to a 30-min social defeat and monitored release of the inhibitory amino acids gamma amino butyric acid (GABA) and taurine within the hypothalamic supraoptic nucleus (SON) using microdialysis. Social defeat caused a significant increase in the release of both GABA and taurine within the SON (up to 480%; P < 0.01 vs. prestress release). To reveal the physiological significance of centrally released GABA, the specific GABAA -receptor antagonist bicuculline (0.02 mm) was administered into the SON via retrodialysis. This approach caused a significant increase in the release of OXT both within the SON and into the blood under basal conditions and during stress (up to 300 and 200%, respectively; P < 0.05 vs. basal values), without affecting plasma vasopressin. Electrophysiological studies confirmed the selective action of bicuculline on the firing activity of OXT neurons in the SON. Taken together, our data demonstrate that GABA is released within the SON during emotional stress to act as a selective inhibitor of both central and peripheral OXT secretion. [source]


Taurine selectively modulates the secretory activity of vasopressin neurons in conscious rats

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2001
Mario Engelmann
Abstract Previous experiments have shown that a 10-min forced swimming session triggers the release of vasopressin from somata and dendrites, but not axon terminals, of neurons of the hypothalamic,neurohypophysial system. To further investigate regulatory mechanisms underlying this dissociated release, we forced male Wistar rats to swim in warm (20 °C) water and monitored release of the potentially inhibitory amino acids gamma amino butyric acid (GABA) and taurine into the hypothalamic supraoptic nucleus using microdialysis. Forced swimming caused a significant increase in the release of taurine (up to 350%; P < 0.05 vs. prestress release), but not GABA. To reveal the physiological significance of centrally released taurine, the specific taurine antagonist 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide was administered into the supraoptic nucleus via retrodialysis. Administration of this antagonist caused a significant increase in the release of vasopressin within the supraoptic nucleus and into the blood both under basal conditions and during stress (up to 800%; P < 0.05 vs. basal values), without affecting hypothalamic or plasma oxytocin. Local administration of the GABAA receptor antagonist bicuculline, in contrast, failed to influence vasopressin secretion at either time point. In a separate series of in vivo electrophysiological experiments, administration of the same dosage of the taurine antagonist into the supraoptic nucleus via microdialysis resulted in an increased electrical activity of identified vasopressinergic, but not oxytocinergic, neurons. Taken together our data demonstrate that taurine is released within the supraoptic nucleus during physical/emotional stress. Furthermore, at the level of the supraoptic nucleus, taurine inhibits not only the electrical activity of vasopressin neurons but also acts as an inhibitor of both central and peripheral vasopressin secretion during different physiological states. [source]


Angiotensin-(1,7) has a dual role on growth-promoting signalling pathways in rat heart in vivo by stimulating STAT3 and STAT5a/b phosphorylation and inhibiting angiotensin II-stimulated ERK1/2 and Rho kinase activity

EXPERIMENTAL PHYSIOLOGY, Issue 5 2008
Jorge F. Giani
Angiotensin (ANG) II contributes to cardiac remodelling by inducing the activation of several signalling molecules, including ERK1/2, Rho kinase and members of the STAT family of proteins. Angiotensin-(1,7) is produced in the heart and inhibits the proliferative actions of ANG II, although the mechanisms of this inhibition are poorly understood. Accordingly, in the present study we examined whether ANG-(1,7) affects the ANG II-mediated activation of ERK1/2 and Rho kinase, STAT3 and STAT5a/b in rat heart in vivo. We hypothesized that ANG-(1,7) inhibits these growth-promoting pathways, counterbalancing the trophic action of ANG II. Solutions of normal saline (0.9% NaCl) containing ANG II (8 pmol kg,1) plus ANG-(1,7) in increasing doses (from 0.08 to 800 pmol kg,1) were administered via the inferior vena cava to anaesthetized male Sprague,Dawley rats. After 5 min, hearts were removed and ERK1/2, Rho kinase, STAT3 and STAT5a/b phosphorylation was determined by Western blotting using phosphospecific antibodies. Angiotensin II stimulated ERK1/2 and Rho kinase phosphorylation (2.3 ± 0.2- and 2.1 ± 0.2-fold increase over basal values, respectively), while ANG-(1,7) was without effect. The ANG II-mediated phosphorylation of ERK1/2 and Rho kinase was prevented in a dose-dependent manner by ANG-(1,7) and disappeared in the presence of the Mas receptor antagonist d -Ala7 -ANG-(1,7). Both ANG II and ANG-(1,7) increased STAT3 and STAT5a/b phosphorylation to a similar extent (130,140% increase). The ANG-(1,7)-stimulated STAT phosphorylation was blocked by the AT1 receptor antagonist losartan and not by d -Ala7 -ANG-(1,7). Our results show a dual action of ANG-(1,7), that is, a stimulatory effect on STAT3 and 5a/b phosphorylation through AT1 receptors and a blocking action on ANG II-stimulated ERK1/2 and Rho kinase phosphorylation through Mas receptor activation. The latter effect could be representative of a mechanism for a protective role of ANG-(1,7) in the heart by counteracting the effects of locally generated ANG II. [source]


Influence of deoxynivalenol on the D -glucose transport across the isolated epithelium of different intestinal segments of laying hens

JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 5-6 2007
W. A. Awad
Summary Deoxynivalenol (DON) decreases glucose absorption in the proximal jejunum of laying hens in vitro and this effect is apparently mediated by the inhibition of the sodium d -glucose co-transporter. DON could modulate the sugar transport of other intestinal regions of chickens. For this purpose, we have measured the effects of DON on the Na+d -glucose co-transporter, by addition of DON after and before a glucose addition in the isolated epithelium from chicken duodenum, jejunum, ileum, caecum and colon by using the Ussing chamber technique in the voltage clamp technique. The data showed in all segments of the gut that the addition of d -glucose on the mucosal side produced an increase in the current (Isc) compared with the basal values, the Isc after glucose addition to the small intestine was greater than the Isc of the large intestine compared with the basal values, specially of the jejunum (p < 0.002), indicating that the jejunum is the segment that is the best prepared for Na+ - d -glucose co-transport. Further addition of 10 ,g DON/ml to the mucosal solution decreased the Isc in all segments and the Isc returned to the basal value, especially in the duodenum and mid jejunum (p < 0.05). In contrast, the addition of 5 mmol d -glucose/l on the mucosal side after incubation of the tissues with DON in all segments had no effect on the Isc (p > 0.05), suggesting that DON previously inhibited the Na+d -glucose co-transport. The blocking effects of DON in duodenum and jejunum were greater than the other regions of the gut. It can be concluded that the small intestine of laying hens has the most relevant role in the carrier mediated glucose transport and the large intestine, having non-significant capacity to transport sugars, appears to offer a minor contribution to glucose transport because the surface area is small. The effect of d -glucose on the Isc was reversed by DON in all segments, especially in the duodenum and jejunum, suggesting that DON entirely inhibited Na+ - d -glucose co-transport. This finding indicates that the inhibition of Na+ co-transport system in all segments could be an important mode of action for DON toxicity of hens. Zusammenfassung Deoxynivalenol (DON) erniedrigt in vitro die Glukoseabsorption im proximalen Jejunum von Legehennen. Dieser Effekt ist vermutlich durch eine Hemmung des Natrium- d -Glukose-Cotransportsystems bedingt. DON könnte außerdem den Glukosetransport in anderen Segmenten des Darms beeinflußen. Zu diesem Zweck haben wir Wirkungen von DON auf das Natrium- d -Glukose-Cotransportsystem gemessen, indem wir DON nach und vor einer Glukosezugabe auf isolierte Darmepithelien des Duodenums, Jejunums, Ileums, Caecums und des Kolons mittels der Ussing-Kammer-Technik in der Volt-Klemmtechnik einwirken ließen. Die erzielten Daten wiesen in allen Segmenten des Darms verglichen mit den Basalwerten einen Anstieg im Strom (Isc) auf, wobei die Isc des Dünndarms bei Glukosegabe signifikant größer als die des Dickdarms waren, was darauf hinweist, dass das Jejunum am besten für den Glukosetransport geeignet war. Eine DON-Zugabe von 10 ,g/ml zur mukosalen Lösung schwächte den Isc in allen Segmenten, wobei die Isc speziell im Duodenum und mittleren Jejunum zum Ausgangswert zurück kehrten. Im Gegensatz dazu brachte die mukosale Glukosezugabe nach der DON-Inkubation keinen signifikanten Anstieg der Isc (p > 0,05), was auf eine durch DON hervorgerufene Blockade des Natrium- d -Glukose-Cotransportsystems schließen ließ. Es kann daraus geschlossen werden, dass der Dünndarm von Legehennen den bedeutendsten Einfluß im Glukosetransportmechanismus nimmt und der Dickdarm aufgrund einer kleineren Oberfläche einen geringeren Beitrag zum Glukosetransport leistet. Dem Isc steigernden Effekt der Glukose konnte signifikant durch DON in den Darmsegmenten besonders im Duodenum und im Jejunum entgegen gewirkt werden, was auf eine umfassende Hemmung des Natrium- d -Glukose-Cotransportsystems hinweist. Die Resultate weisen darauf hin, dass eine Hemmung des Natrium- d -Glukose-Cotransportsystems in allen Darmsegmenten eine wichtige Rolle in der DON-Toxizität für die Henne darstellen könnte. [source]


Immunotoxicity of acute acephate exposure in control or IL-1-challenged rats: correlation between the immune cell composition and corticosteroid concentration in blood

JOURNAL OF APPLIED TOXICOLOGY, Issue 5 2002
Ashok K. Singh
Abstract Corticosterone concentration and the immune cell composition were measured in rats exposed by intraperitoneal (i.p.) injection to different doses (10,500 mg kg,1) of acephate (Ace) and 250 µg kg,1 of interleukin 1 (IL-1), either alone or in combination. Two different combination protocols were used: IL-1 and Ace were administered simultaneously; and IL-1 was injected 60 min after Ace administration (sequential exposure). Ace, in a dose- and time-dependent manner, inhibited blood and brain acetylcholinesterase (AChE) activities, increased blood corticosterone concentrations, suppressed blood CD4, CD8, B cell and monocyte contents and increased blood neutrophil counts. The Ace-induced changes lasted for up to 24 h after Ace exposure. Interleukin 1 increased blood corticosterone concentrations without affecting blood or brain AChE activities. The IL-1-induced corticosterone concentration returned to the basal level within 3,10 h after IL-1 exposure. The CD4, CD8, B cell and monocyte counts increased significantly at 10 min after IL-1 exposure. The cell counts decreased gradually thereafter and returned to the basal level within 30 min after IL-1 exposure. Simultaneous exposure of rats to Ace and IL-1 partially suppressed the IL-1-induced increase in the immune cell counts and decreased the immune cell numbers below the basal values. Sequential injection of Ace and IL-1 blocked the IL-1-induced increase in the immune cell numbers. Thus, Ace exposure would impair the normal distribution of immune cells and deregulate the IL-1 response in rats. This study therefore suggests that Ace would suppress the immune cell numbers in blood, thus decreasing an organism's immunity. Ace exposure occurring concurrent with injury would augment the acute-phase response, which would augment the toxic effects of IL-1 and other cytokines, and Ace exposure occurring prior to the injury would suppress or abolish the initial stimulatory effects of IL-1, which would decrease an organism's ability to combat infection or injury. Copyright © 2002 John Wiley & Sons, Ltd. [source]


Relationship between non-functional masticatory activity and central dopamine in stressed rats

JOURNAL OF ORAL REHABILITATION, Issue 11 2010
F. M. GÓMEZ
Summary, In humans, diurnal tooth-clenching and other oral stereotyped behaviour are associated with stress/anxiety. In rodents, gnawing/biting of objects is observed during exposure to stress. Both nigrostriatal and mesocortical dopaminergic systems are involved in the development of this coping behaviour. To clarify the relationship between central dopaminergic activity and stress-induced parafunctional masticatory behaviour, using microdialysis in vivo, we assessed the changes in extracellular dopamine concentrations in both prefrontal cortex and striatum of rats subjected to a mild tail pinch. The animals were divided into two groups according to the degree of non-functional masticatory activity (NFMA) displayed during exposure to tail pinch. In prefrontal cortex, rats which displayed severe NFMA showed a greater increase in extracellular dopamine concentration in relation to basal values (Emax = 184 ± 26%) than those which did not display this coping behaviour (Emax = 139 ± 23%) (FNFMA[1,86] = 3·97; P < 0·05) (n = 17). A positive association was also found between cortical dopamine maximal value from baseline and the degree of NFMA displayed (r = 0·36; P < 0·05) (n = 17). There were no significant differences in the tail-pinch-induced striatal dopamine increase between both groups of rats (Emax = 130 ± 10%) (n = 17). These results provide further evidence in support of prefrontal dopamine playing a relevant role in the expression of stress-induced masticatory coping behaviour. [source]


Expression of interferon-, subtypes in peripheral mononuclear cells from patients with chronic hepatitis C: a role for interferon-,5

JOURNAL OF VIRAL HEPATITIS, Issue 2 2001
E. Larrea
Interferon (IFN)-, is a family of antiviral proteins encoded by different genes. The biological significance of the existence of various IFN-, subtypes is not clear. We have investigated the interferon system in chronic hepatitis C virus (HCV) infection, a disease that responds to interferon-,2 therapy in only a limited proportion of cases. We analysed the expression of interferon regulatory factor (IRF)-1, IRF-2, and IFN-, subtypes in nonstimulated and Sendai virus-stimulated peripheral blood mononuclear cells (PBMC) from HCV infected patients and healthy controls. We observed that the IRF-1 mRNA and IRF-1/IRF-2 ratios were increased in PBMC from hepatitis C patients with respect to normal subjects. Sendai virus stimulation of PBMC led to a significant increase in the levels of IRF-1, IRF-2 and IFN-, mRNAs and in the production of IFN-, protein with respect to basal values in healthy controls as well as in patients with HCV infection. In addition, we found that while natural HCV infection induced increased IFN-,5 expression in PBMC, in vitro infection of these cells with Sendai virus caused a raise in the expression of IFN-,8 in both patients and normal controls. In summary, our results indicate that virus-induced activation of the IFN system in human PBMC is associated with selective expression of individual IFN-, subtypes, IFN-,5 being the specific subtype induced in PBMC from patients with chronic HCV infection. [source]


Potential Use of Biomarkers in Zooplankton as Early Warning Signals of Ecotoxicological Risk in the Marine Food Chain

MARINE ECOLOGY, Issue 2002
Roberta Minutoli
Abstract. Zooplankton is an essential component of the marine and brackish food chains. The ecotoxicological risk of zooplanktonic communities, estimated by the modern methodological approach of biomarkers, can be used as an early warning signal of ecosystem health. The aim of this project is to estimate the potential use of several biomarkers (esterases, mixed function oxidases, porphyrins) in zooplanktonic organisms. Studies were carried out with different zooplanktonic crustaceans: the copepods Acartia margalefi and Acartia latisetosa collected in Ganzirri Lake (Messina); the mysid Siriella clausi collected in Faro Lake (Messina); the mysids Diamysis bahirensis, Siriella armata and Mysidopsis gibbosa collected in Stagnone di Marsala (Palermo); the Antarctic euphausiids Euphausia crystallorophias and Euphausia superba; the am-phipod Streetsia challengeri and the euphausiid Meganycthiphanes norvegica collected after a shore-stranding along Messina's Ionian coast. Moreover, experiments were carried out with the benthic decapods Eriphia verrucosa and Pachygrapsus marmoratus from a rocky shore of Messina's Ionian coast. Acetylcholinesterase activity (AChE) was determined in homogenates of whole organisms. The key result of this project concerns the different AChE activity basal values of different crustacean species. Particular attention should be paid to the difference in basal activity found between the Antarctic and the Mediterranean species. [source]


Protective effect of resveratrol on markers of oxidative stress in human erythrocytes subjected to in vitro oxidative insult

PHYTOTHERAPY RESEARCH, Issue S1 2010
Kanti Bhooshan Pandey
Abstract Resveratrol is a natural polyphenolic compound found largely in the skin of red grapes. Growing evidence suggests that resveratrol may play an important role in the prevention of many human diseases. Many of the biological actions of this polyphenol have been attributed to its antioxidant properties. The present study was undertaken to evaluate the effect of resveratrol on intracellular reduced glutathione (GSH) and membrane sulphydryl groups in erythrocytes subjected to oxidative stress in vitro by incubating with t-BHP (10 µm). The study was aimed to test the efficacy of the antioxidant effect of resveratrol on human erythrocytes. Subjecting erythrocytes to oxidative stress (in vitro) by incubating them with t-BHP (10 µm) caused a significant decrease in the intracellular GSH level and membrane ,SH content compared with basal values. Incubation of erythrocytes/membranes with resveratrol (1,100 µm final conc) resulted in significant protection against the t-BHP-induced oxidative stress as evidenced by the increase in GSH level and membrane ,SH content. It was observed that the effect of resveratrol is dose/concentration and time-dependent. Since resveratrol is naturally present in many fruits and vegetables, a diet rich in resveratrol may provide protection against degenerative diseases. Copyright © 2009 John Wiley & Sons, Ltd. [source]


Basal serum testosterone as an indicator of response to clomiphene treatment in human epididymis, seminal vesicles and prostate

ANDROLOGIA, Issue 5 2002
Dr. G. F. GonzalesArticle first published online: 13 AUG 200
Summary. The present study was designed to determine the response of human epididymis, seminal vesicles and prostate function after a 5-day course of clomiphene citrate in men attending an infertility service. In 45 men, the secretions of the epididymis, seminal vesicles and prostate were assessed by measurements of seminal ,-glucosidase, fructose and acid phosphatase, respectively. Subjects were classified as normal or abnormal: abnormal men were defined as those who either had history of a sexually transmitted disease (STD), leukocytosper-mia, hypoandrogenism, or a low response of Leydig cells to clomiphene stimulation; and normal subjects were those who did not have these conditions. Mean serum testosterone luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels were significantly increased after the short course with clomiphene citrate. After clomiphene citrate stimulation, the men in the normal group showed significantly increased marker levels of the seminal vesicles (P <0.02) and prostate (P <0.05), but not of the epididymis (P: NS). Men classified as abnormal showed no response according to the markers of the seminal vesicles and epididymis. Men with history of STD and abnormal basal values of acid phosphatase did not respond to the treatment. Men with history of STD but normal basal values of seminal acid phosphatase increased significantly in their levels of seminal acid phosphatase after clomiphene stimulation (P <0.02). Multivariate analysis showed that the basal serum testosterone level was the only variable in predicting the probability of response to the clomiphene in terms of true-corrected seminal fructose, seminal acid phosphatase and seminal ,-glucosidase levels. In fact, a high response of the seminal vesicles was observed in men with the highest basal serum testosterone levels (0.45 *** 0.17; coefficient of regression *** standard error; P <0.018). However, a high response in terms of seminal acid phosphatase (P <0.004) or ,-glucosidase (P <0.037) was observed in men with low basal serum testosterone levels. In conclusion, in the normal men, true-corrected fructose and acid phosphatase but not ,-glucosidase in semen increased after duplicate androgen stimulation. An absence of response was observed in cases with history of STD/leukocytospermia or hypoandrogenism. [source]


Benefits of using the probiotic Efinol®L during transportation of cardinal tetra, Paracheirodon axelrodi (Schultz), in the Amazon

AQUACULTURE RESEARCH, Issue 2 2009
Levy Carvalho Gomes
Abstract The objective of this experiment was to test the probiotic Efinol®L during transportation of cardinal tetra, Paracheirodon axelrodi (Schultz). For the transportation, fish were distributed in 18 plastic tanks, of which nine contained the Efinol®L (10 mg L,1; probiotic treatment) and the remaining had no probiotic (control treatment). Transport lasted 24 h and three different boxes of each treatment were sampled at 3, 12 and 24 h. Up to the 12-h sampling period, no significant difference in the survival was observed; on the other hand, survival was higher at the end of the transport (24 h) in the probiotic treatment. No significant difference was found in dissolved oxygen and temperature between treatments. Conductivity, pH and alkalinity increased along the transport, but without a difference between treatments. Ammonia increased in all treatments, although it was significantly lower in the probiotic group at 24 h. Cortisol levels were significantly higher in all transported fish when compared with the basal values. At 24 h, cortisol levels in control fish were significantly higher than those in the probiotic treatment. With the observed results, we are able to conclude that the probiotic Efinol®L is efficient during cardinal transport, lowering the mortality and helping maintain water quality possibly by lowering metabolic wastes. [source]


Pharmacokinetics and pharmacodynamics of TF-505, a novel nonsteroidal 5,-reductase inhibitor, in normal subjects treated with single or multiple doses

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 3 2002
Tomoe Fujita
Aims To assess the tolerability, pharmacokinetics and pharmacodynamics of a novel nonsteroidal,, and,, noncompetitive,, inhibitor,, of,, type,, I,, and,, type,, II,, 5,-reductases, (,)-(S)-4-[1-[4-[1-(4-isobutylphenyl) butoxy]benzoyl]indolizin-3-yl]butyric acid (TF-505), after single and multiple oral doses in healthy volunteers. Methods In the single-dose study, six young adult males in each dose group received 25 mg or 50 mg of TF-505, and six older males (, 40 years) in each dose group received 75 mg or 100 mg of TF-505. The subjects were given the drug in ascending dose and in the fasting state. Six subjects also received 50 mg of TF-505 after breakfast in a two-period crossover manner. In the multiple-dose study, six older males in each dose group received 12.5 mg or 25 mg TF-505 after breakfast daily for 7 days. Plasma concentrations of TF-505, dihydrotestosterone (DHT) and testosterone were measured. The pharmacokinetics of TF-505 were analysed by a compartment model with first-order absorption, first-order elimination and a lag time. Pharmacokinetic and pharmacodynamic relationships were evaluated by indirect response modelling with inhibition of input. Results Maximum plasma concentration (Cmax) and the area under the concentration,time curve (AUC) increased proportionately after the single dose up to 50 mg and with the multiple doses. Linearity was not detected between 75 and 100 mg of TF-505. Dose dependency was also noted for the effect of TF-505 on DHT concentrations following single doses up to 50 mg and multiple doses. Plasma DHT concentrations decreased maximally to 58.2, 49.5, 54.2 and 49.8% of basal values at 8,12 h after single administration of 25, 50, 75 and 100 mg TF-505, respectively, and to 60.5 and 49.4% at the 7th and 5th dose following multiple doses of 12.5 and 25 mg TF-505, respectively. The predicted effect curves matched the observed data when the indirect response model was applied to the time course of the suppressant effect of TF-505 on plasma DHT concentrations after both the single and multiple studies. Fifty percent inhibitory concentrations (IC50) of 0.82, 1.48, 1.31 and 0.88 µ g ml,1, zero-order rate constants for the onset of plasma DHT concentration changes (kin) of 17.8, 17.4, 17.0 and 10.7% h,1 and first-order rate constants,, for,, increase,, in,, plasma,, DHT,, concentrations,, to,, basal,, values,, (kout),, of,, 0.17,,, 0.16,,, 0.17,, and,, 0.10 h,1,, for,, the,, single,, study,, at,, doses,, of,, 25,,, 50,,, 75,, and 100 mg, respectively, were attained. In the multiple-dose study, IC50s were 1.74 and 1.49 µg ml,1 for the 12.5 and 25 mg doses, respectively. No serious adverse events related to TF-505 were observed. Conclusions TF-505 was well tolerated in healthy male volunteers. Accumulation of TF-505 in plasma was not observed during multiple dosing. The indirect response model described the relationships between pharmacokinetics and pharmacodynamics of TF-505. Such modelling is expected to yield an appropriate dosage regimen in subsequent clinical trials. [source]


Nitric oxide (NO) modulation of PAF-induced cardiopulmonary action: interaction between NO synthase and cyclo-oxygenase-2 pathways

BRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2001
Fulvia Fabi
To further investigate into the mechanisms of PAF-induced cardiopulmonary actions, we examined the effects of the nitric oxide synthase (NOS) inhibitor L -N, -nitro- L -arginine (L -NNA), of the specific cyclooxygenase-2 (COX-2) inhibitor NS 398, and of the combined presence of both COX and NOS inhibitors on the PAF responses in the heart lung preparation of guinea-pig (HLP). In HLPs perfused with homologous blood, dose-response curves for the haemodynamic and bronchial effects of PAF (1 , 32 ng) were carried out in the absence or presence of L -NNA (200 ,M). L -NNA caused an increase in the resting pulmonary arterial pressure (PAP) without affecting the other basal values, and strongly potentiated the bronchoconstriction and pulmonary hypertension elicited by PAF. An enhancement of the PAF-induced actions on right atrial pressure (RAP) and cardiac output (CO) was also observed. All the effects of L -NNA were antagonized by L -arginine (2 mM). The presence of L -NNA in the perfusing blood of HLPs failed to affect the pulmonary hypertensive and bronchoconstrictor responses induced by the thromboxane A2 mimetic U46619 (0.05 , 1.6 ,g), 5-hydroxytryptamine (0.1 , 1.6 ,g), and histamine (0.1 , 1.6 ,g), thus suggesting that these PAF secondary mediators are not responsible for the hyper-responsiveness to PAF induced by L -NNA. Blocking COX-2 pathway with NS 398 (15 , 30 ,M) did not alter the cardiopulmonary resting variables. However, a reduction of the PAF-mediated pulmonary hypertension, but not of bronchoconstriction, was observed. When L -NNA was added to the perfusing medium of HLPs pre-treated with NS 398 or with indomethacin (15 ,M), the basal PAP values were enhanced. However, in the combined presence of COX and NOS inhibitors, only a slight increase in the hypertensive responses to the highest doses of PAF was observed, whereas the PAF mediated actions at bronchial and cardiac level were unaffected. This study indicates that (i) the cardiopulmonary actions induced by PAF are specifically modulated by endogenous NO through the NOS pathway, and (ii) COX-2 isoform is involved in the pulmonary hypertensive, but not bronchoconstrictor, effects of PAF. Furthermore, an interaction between PAF stimulated COX, particularly COX-2, and NOS pathways appears to take a functional role at both bronchial and cardiovascular level. British Journal of Pharmacology (2001) 134, 777,788; doi:10.1038/sj.bjp.0704311 [source]


Carbohydrate antigen 19-9 change during chemotherapy for advanced pancreatic adenocarcinoma

CANCER, Issue 12 2009
Michele Reni MD
Abstract BACKGROUND: Radiologic assessment of tumor response in pancreatic cancer is complicated by desmoplastic reactions within or around the tumor. The objective of this study was to evaluate the correlation between a decline in carbohydrate antigen 19-9 (CA 19-9) and survival in patients with advanced pancreatic cancer who received upfront chemotherapy. METHODS: CA 19-9 serum basal values were measured in 247 patients with advanced pancreatic cancer who were enrolled in 5 consecutive trials between 1997 and 2007. Survival curves were compared among patients who had a predefined CA 19-9 nadir variation (<50%. Group 1; 50% to 89%, Group 2; or >89%, Group 3). To eliminate guarantee-time bias, survival analysis was repeated using the landmark method. RESULTS: In both univariate and multivariate analysis, the basal CA 19-9 value significantly predicted survival. The median survival was 15.5 months for 34 patients who had normal basal CA 19-9 values, 11.9 months for 108 patients who had basal values between 38 U/mL and 1167 U/mL, and 8 months for 105 patients who had basal values >1167 U/mL. At least 1 CA 19-9 follow-up value was available for 204 patients who had baseline values greater than normal. A significant difference in overall survival was observed in univariate and multivariate analyses between Groups 1 and 2, between Groups 1 and 3, and between Groups 2 and 3. The results were confirmed using the landmark method. CONCLUSIONS: In this study, baseline CA 19-9 was confirmed as an independent prognostic factor for survival, and it may be considered as a stratification factor in trials in patients with advanced pancreatic cancer. Biochemical response may be used as a complementary measure to radiologic response to provide a better assessment of chemotherapy activity and to drive treatment decisions in clinical practice. Cancer 2009. © 2009 American Cancer Society. [source]


X-Irradiation Induces Up-regulation of ATM Gene Expression in Wild-type Lymphoblastoid Cell Lines, but Not in Their Heterozygous or Homozygous Ataxia-telangiectasia Counterparts

CANCER SCIENCE, Issue 6 2001
Yuko Hirai
Ataxia-telangiectasia (AT) is an autosomal recessive disease. The relevant gene has been cloned and designated ATM. We studied the expression of both ATM mRNA and the ATM protein in unirradi-ated and X-irradiated EBV (Epstein-Barr virus)-transformed lymphoblastoid cell lines (LCLs) derived from donors who were normal (ATM+/+), AT heterozygotes (ATM+/,), or AT homozy-gotes (ATM,/,), respectively. In ATM+/+ LCLs, the levels of ATM mRNA were found to have increased by approximately 1.5-fold within 1 h of exposure to 10 Gy of X-rays, while the ATM protein levels had increased by 1.5- to 2.0-fold within 2 to 3 h of irradiation. The wild-type mRNA and protein levels both returned to their basal values fairly quickly after this tune. The results obtained with the ATM+/, LCLs were quite different, however: neither the mRNA nor protein levels were found to have increased as a consequence of X-irradiation in any ATM+/, LCL. Twelve of the mutations in the ATM,/, LCLs we used were truncating mutations, and we suspected that the corresponding truncated ATM proteins would be too labile to be detected by western blot analysis. However, five of the ATM,/, LCLs produced mutant ATM proteins that were identical in molecular weight to the wild-type ATM protein. When cells from three of these five clones were exposed to X-rays, transcription of the mutant ATM genes appeared to reduce somewhat, as were the levels of protein being produced. These results suggest that the normal ATM gene responds to ionizing radiation by up-regulating its activity, whereas none of the mutant ATM genes we studied were able to respond in this way. [source]


Stereospecific activity of two glutamate analogs

CHIRALITY, Issue 9 2004
Juan Manuel Araujo Alvarez
Abstract Two glutamic acid analogs, (+)-(S)- and (,)-(R)-4-(2,2-diphenyl-1,3,2-oxazaborolidin-5-oxo)propionic acid ((+)-(S)- and (,)-(R)-Trujillon, respectively), were prepared. The stereospecific activity of their pharmacological properties was studied. The median convulsant dose (CD50) and median lethal dose (LD50) were analyzed in female Swiss Webster mice and their effects in vivo on unitary electrical activity in globus pallidus neurons were elucidated in male Wistar rats. Compounds were characterized by 1H, 13C, and 11B nuclear magnetic resonance. The LD50 of (+)-(S)-Trujillon was 449.08 mg/kg and it increased spontaneous motor activity, while with (,)-(R)-Trujillon there was no mortality up to 1,000 mg/kg and it decreased spontaneous motor activity. The CD50 in experiments with (+)-(S)-Trujillon was 199.34 mg/kg. Unitary recording in globus pallidus neurons showed i.v. administration (+)-(S)-Trujillon (50 mg/kg) increased frequency 79.0 ± 23.0% in relation to basal response. (,)-(R)-Trujillon and (+)-(S)-glutamate (50 mg/kg each) did not provoke changes in spontaneous basal firing. Local infusion of (+)-(S)-Trujillon (1 nMol) increased spontaneous firing in most neurons tested by 269.0 ± 83.0% in relation to basal values. Intrapallidal infusion of (,)-(R)-Trujillon (1 nMol) and saline solution did not cause statistically significant changes in globus pallidus spiking. Results showed that (+)-(S)-Trujillon crosses the blood,brain barrier and has stereospecific activity. Chirality 16:586,591, 2004. © 2004 Wiley-Liss, Inc. [source]


Antioxidants and narrow band-UVB in the treatment of vitiligo: a double-blind placebo controlled trial

CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 6 2007
M. L. Dell'Anna
Summary Background., Vitiligo is an acquired depigmenting disease with uncertain aetiopathogenesis, possibly associated with oxidative stress. Narrowband ultraviolet B phototherapy (NB-UVB) is the most widely used and effective treatment. Aim., To evaluate the clinical effectiveness of NB-UVB and the repairing of oxidative stress-induced damage, using oral supplementation with an antioxidant pool (AP). Methods., Patients (n = 35) with nonsegmental vitiligo were enrolled in a randomized, double-blind, placebo-controlled multicentre trial. The treatment group received, for 2 months before and for 6 months during the NB-UVB treatment, a balanced AP containing ,-lipoic acid, vitamins C and E, and polyunsaturated fatty acids. The area and number of lesions, as well as some parameters of the oxidation,reduction (redox) status of the peripheral blood mononuclear cells (PBMCs) were estimated at the beginning, after 2 months, and at the end of the trial. Results., In total, 28 patients completed the study. After 2 months of AP supplementation, the catalase activity and the production of reactive oxygen species (ROS) were 121% and 57% of the basal values (P < 0.05 and P < 0.02 vs. placebo, respectively). The AP increased the therapeutic success of NB-UVB, with 47% of the patients obtaining >,75% repigmentation vs. 18% in the placebo group (P < 0.05). An increase in catalase activity to 114% (P < 0.05 vs. placebo) and decrease in ROS level of up to 60% (P < 0.02 vs. placebo) of the basal value was observed in PBMCs. Finally, the AP intake maintained the membrane lipid ratio (saturated : unsaturated fatty acids 1.8 : 3.1; P < 0.05), counteracting phototherapy-induced saturation. Conclusions., Oral supplementation with AP containing ,-lipoic acid before and during NB-UVB significantly improves the clinical effectiveness of NB-UVB, reducing vitiligo-associated oxidative stress. [source]