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Compensatory Response (compensatory + response)
Selected AbstractsIntrauterine growth restriction reduces nephron number and renal excretory function in newborn piglets,ACTA PHYSIOLOGICA, Issue 2 2002R. Bauer ABSTRACT To examine the effects of intrauterine growth restriction on nephron number, renal circulation, and renal excretory functions in newborns, studies were conducted on 1-day-old anaesthetized piglets, divided into normal weight (n = 6) and intrauterine growth restricted (n = 6) piglets. Renal blood flow was measured by coloured microspheres, glomerular filtration rate was measured by inulin clearance, and osmotic clearance and fractional sodium excretion were calculated. In addition, an estimation of the nephron number was performed by counting representative glomerular numbers in microscopic sections. Newborn intrauterine growth restricted piglets exhibited a reduced glomerular filtration rate and osmotic clearance (P < 0.05), whereas renal blood flow and the filtration fraction as well as fractional sodium excretion were similar in normal weight and intrauterine growth restricted piglets. The nephron number was markedly reduced in intrauterine growth restricted piglets even if the nephron number was related to body weight (P < 0.01). There was a positive correlation between nephron number and glomerular filtration rate (r = 0.69, P < 0.05). Reduced glomerular filtration rate of newborn intrauterine growth restricted piglets is associated with a reduced nephron number. Thus, at birth, compensatory response of renal function due to nephron deficit does not exist in intrauterine growth restricted piglets. [source] Aquaporin 4 changes in rat brain with severe hydrocephalusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2006Xiaoyan Mao Abstract Hydrocephalus is characterized by impaired cerebrospinal fluid (CSF) flow with enlargement of the ventricular cavities of the brain and progressive damage to surrounding tissue. Bulk water movement is altered in these brains. We hypothesized that increased expression of aquaporins, which are water-permeable channel proteins, would occur in these brains to facilitate water shifts. We used quantitative (real-time) RT-PCR, Western blotting and immunohistochemistry to evaluate the brain expression of aquaporins (AQP) 1, 4, and 9 mRNA and protein in Sprague,Dawley rats rendered hydrocephalic by injection of kaolin into cistern magna. AQP4 mRNA was significantly up-regulated in parietal cerebrum and hippocampus 4 weeks and 9 months after induction of hydrocephalus (P < 0.05). Although Western blot analysis showed no significant change, there was more intense perivascular AQP4 immunoreactivity in cerebrum of hydrocephalic brains at 3,4 weeks after induction. We did not detect mRNA or protein changes in AQP1 (located in choroid plexus) or AQP9 (located in select neuron populations). Kir4.1, a potassium channel protein linked to water flux, exhibited enhanced immunoreactivity in the cerebral cortex of hydrocephalic rats; the perineuronal distribution was entirely different from that of AQP4. These results suggest that brain AQP4 up-regulation might be a compensatory response to maintain water homeostasis in hydrocephalus. [source] Rapid and long-term alterations of hippocampal GABAB receptors in a mouse model of temporal lobe epilepsyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2003Andrea Straessle Abstract Alterations of ,-aminobutyric acid (GABA)B receptor expression have been reported in human temporal lobe epilepsy (TLE). Here, changes in regional and cellular expression of the GABAB receptor subunits R1 (GBR1) and R2 (GBR2) were investigated in a mouse model that replicates major functional and histopathological features of TLE. Adult mice received a single, unilateral injection of kainic acid (KA) into the dorsal hippocampus, and GABAB receptor immunoreactivity was analysed between 1 day and 3 months thereafter. In control mice, GBR1 and GBR2 were distributed uniformly across the dendritic layers of CA1,CA3 and dentate gyrus. In addition, some interneurons were labelled selectively for GBR1. At 1 day post-KA, staining for both GBR1 and GBR2 was profoundly reduced in CA1, CA3c and the hilus, and no interneurons were visible anymore. At later stages, the loss of GABAB receptors persisted in CA1 and CA3, whereas staining increased gradually in dentate gyrus granule cells, which become dispersed in this model. Most strikingly, a subpopulation of strongly labelled interneurons reappeared, mainly in the hilus and CA3 starting at 1 week post-KA. In double-staining experiments, these cells were selectively labelled for neuropeptide Y. The number of GBR1-positive interneurons also increased contralaterally in the hilus. The rapid KA-induced loss of GABAB receptors might contribute to epileptogenesis because of a reduction in both presynaptic control of transmitter release and postsynaptic inhibition. In turn, the long-term increase in GABAB receptors in granule cells and specific subtypes of interneurons may represent a compensatory response to recurrent seizures. [source] The functional neuroanatomy of geriatric depressionINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 8 2009Gwenn S. Smith Abstract Objective Positron Emission Tomography (PET) studies of cerebral glucose metabolism have demonstrated sensitivity in evaluating the functional neuroanatomy of treatment response variability in depression, as well as in the early detection of functional changes associated with incipient cognitive decline. The evaluation of cerebral glucose metabolism in late life depression may have implications for understanding treatment response variability, as well as evaluating the neurobiological basis of depression in late life as a risk factor for dementia. Methods Sixteen patients with geriatric depression and 13 comparison subjects underwent resting PET studies of cerebral glucose metabolism, as well as magnetic resonance (MR) imaging scans to evaluate brain structure. Results Cerebral glucose metabolism was elevated in geriatric depressed patients relative to comparison subjects in anterior (right and left superior frontal gyrus) and posterior (precuneus, inferior parietal lobule) cortical regions. Cerebral atrophy (increased cerebrospinal fluid [CSF] and decreased grey and white matter volumes) were observed in some of these regions, as well. Regional cerebral metabolism was positively correlated with severity of depression and anxiety symptoms. Conclusions In contrast to decreased metabolism observed in normal aging and neurodegenerative conditions such as Alzheimer's disease, cortical glucose metabolism was increased in geriatric depressed patients relative to demographically matched controls, particularly in brain regions in which cerebral atrophy was observed, which may represent a compensatory response. Copyright © 2009 John Wiley & Sons, Ltd. [source] Activation of the PI3K/Akt signal transduction pathway and increased levels of insulin receptor in protein repair-deficient miceAGING CELL, Issue 1 2005Christine Farrar Summary Protein l -isoaspartate (d -aspartate) O -methyltransferase is an enzyme that catalyses the repair of isoaspartyl damage in proteins. Mice lacking this enzyme (Pcmt1,/, mice) have a progressive increase in brain size compared with wild-type mice (Pcmt1+/+ mice), a phenotype that can be associated with alterations in the PI3K/Akt signal transduction pathway. Here we show that components of this pathway, including Akt, GSK3, and PDK-1, are more highly phosphorylated in the brains of Pcmt1,/, mice, particularly in cells of the hippocampus, in comparison with Pcmt1+/+ mice. Examination of upstream elements of this pathway in the hippocampus revealed that Pcmt1,/, mice have increased activation of insulin-like growth factor-I (IGF-I) receptor and/or insulin receptor. Western blot analysis revealed an approximate 200% increase in insulin receptor protein levels and an approximate 50% increase in IGF-I receptor protein levels in the hippocampus of Pcmt1,/, mice. Higher levels of the insulin receptor protein were also found in other regions of the adult brain and in whole tissue extracts of brain, liver, heart and testes of both juvenile and adult Pcmt1,/, mice. There were no significant differences in plasma insulin levels for adult Pcmt1,/, mice during glucose tolerance tests. However, they did show higher peak levels of blood glucose, suggesting a mild impairment in glucose tolerance. We propose that Pcmt1,/, mice have altered regulation of the insulin pathway, possibly as a compensatory response to altered glucose uptake or metabolism or as an adaptive response to a general accumulation of isoaspartyl protein damage in the brain and other tissues. [source] Linking marine and freshwater growth in western Alaska Chinook salmon Oncorhynchus tshawytschaJOURNAL OF FISH BIOLOGY, Issue 6 2009G. T. Ruggerone The hypothesis that growth in Pacific salmon Oncorhynchus spp. is dependent on previous growth was tested using annual scale growth measurements of wild Chinook salmon Oncorhynchus tshawytscha returning to the Yukon and Kuskokwim Rivers, Alaska, from 1964 to 2004. First-year marine growth in individual O. tshawytscha was significantly correlated with growth in fresh water. Furthermore, growth during each of 3 or 4 years at sea was related to growth during the previous year. The magnitude of the growth response to the previous year's growth was greater when mean year-class growth during the previous year was relatively low. Length (eye to tail fork, LETF) of adult O. tshawytscha was correlated with cumulative scale growth after the first year at sea. Adult LETF was also weakly correlated with scale growth that occurred during freshwater residence 4 to 5 years earlier, indicating the importance of growth in fresh water. Positive growth response to previous growth in O. tshawytscha was probably related to piscivorous diet and foraging benefits of large body size. Faster growth among O. tshawytscha year classes that initially grew slowly may reflect high mortality in slow growing fish and subsequent compensatory growth in survivors. Oncorhynchus tshawytscha in this study exhibited complex growth patterns showing a positive relationship with previous growth and a possible compensatory response to environmental factors affecting growth of the age class. [source] Altered apolipoprotein E glycosylation is associated with A,(42) accumulation in an animal model of Niemann-Pick Type C diseaseJOURNAL OF NEUROCHEMISTRY, Issue 6 2010Ching-Ching Chua J. Neurochem. (2010) 112, 1619,1626. Abstract Neurodegeneration is the final cause of death in Niemann-Pick Type C (NPC) disease, a cholesterol-storage disorder. Accumulating evidence indicates that NPC may share common pathological mechanisms with Alzheimer's disease, including the link between aberrant cholesterol metabolism and amyloid-, (A,) deposition. Apolipoprotein E (apoE) is highly expressed in the brain and plays a pivotal role in cholesterol metabolism. ApoE can also modulate A, production and clearance, and it is a major genetic risk factor for Alzheimer's disease. Although apoE is glycosylated, the functional significance of this chemical alteration on A, catabolism is unclear. In this study using an NPC animal model, we detect specific changes in apoE glycosylation that correlate with increased A,(42) accumulation prior to the appearance of neurological abnormalities. This suggests that increased apoE expression could be a compensatory response to the increased A,(42) deposition in NPCnih mice. We also observe what appears to be a simplification of the glycosylation process on apoE during neurodegeneration. [source] Effects of chronic paroxetine treatment on dialysate serotonin in 5-HT1B receptor knockout miceJOURNAL OF NEUROCHEMISTRY, Issue 1 2003A. M. Gardier Abstract The role of serotonin (5-HT)1B receptors in the mechanism of action of selective serotonin re-uptake inhibitors (SSRI) was studied by using intracerebral in vivo microdialysis in conscious, freely moving wild-type and 5-HT1B receptor knockout (KO 5-HT1B) mice in order to compare the effects of chronic administration of paroxetine via osmotic minipumps (1 mg per kg per day for 14 days) on extracellular 5-HT levels ([5-HT]ext) in the medial prefrontal cortex and ventral hippocampus. Basal [5-HT]ext values in the medial prefrontal cortex and ventral hippocampus, ,,20 h after removing the minipump, were not altered by chronic paroxetine treatment in both genotypes. On day 15, in the ventral hippocampus, an acute paroxetine challenge (1 mg/kg i.p.) induced a larger increase in [5-HT]ext in saline-pretreated mutant than in wild-type mice. This difference between the two genotypes in the effect of the paroxetine challenge persisted following chronic paroxetine treatment. Conversely, in the medial prefrontal cortex, the paroxetine challenge increased [5-HT]ext similarly in saline-pretreated mice of both genotypes. Such a challenge produced a further increase in cortical [5-HT]ext compared with that in saline-pretreated groups of both genotypes, but no differences were found between genotypes following chronic treatment. To avoid the interaction with raphe 5-HT1A autoreceptors, 1 µm paroxetine was perfused locally through the dialysis probe implanted in the ventral hippocampus; similar increases in hippocampal [5-HT]ext were found in acutely or chronically treated wild-type mice. Systemic administration of the mixed 5-HT1B/1D receptor antagonist GR 127935 (4 mg/kg) in chronically treated wild-type mice potentiated the effect of a paroxetine challenge dose on [5-HT]ext in the ventral hippocampus, whereas systemic administration of the selective 5-HT1A receptor antagonist WAY 100635 did not. By using the zero net flux method of quantitative microdialysis in the medial prefrontal cortex and ventral hippocampus of wild-type and KO 5-HT1B mice, we found that basal [5-HT]ext and the extraction fraction of 5-HT were similar in the medial prefrontal cortex and ventral hippocampus of both genotypes, suggesting that no compensatory response to the constitutive deletion of the 5-HT1B receptor involving changes in 5-HT uptake capacity occurred in vivo. As steady-state brain concentrations of paroxetine at day 14 were similar in both genotypes, it is unlikely that differences in the effects of a paroxetine challenge on hippocampal [5-HT]ext are due to alterations of the drug's pharmacokinetic properties in mutants. These data suggest that there are differences between the ventral hippocampus and medial prefrontal cortex in activation of terminal 5-HT1B autoreceptors and their role in regulating dialysate 5-HT levels. These presynaptic receptors retain their capacity to limit 5-HT release mainly in the ventral hippocampus following chronic paroxetine treatment in mice. [source] Hypothalamic-Pituitary-Adrenal Axis Abnormalities in Response to Deletion of 11,-HSD1 is Strain-DependentJOURNAL OF NEUROENDOCRINOLOGY, Issue 11 2009R. N. Carter Inter-individual differences in hypothalamic-pituitary-adrenal (HPA) axis activity underlie differential vulnerability to neuropsychiatric and metabolic disorders, although the basis of this variation is poorly understood. 11,-Hydroxysteroid dehydrogenase type 1 (11,-HSD1) has previously been shown to influence HPA axis activity. 129/MF1 mice null for 11,-HSD1 (129/MF1 HSD1,/,) have greatly increased adrenal gland size and altered HPA activity, consistent with reduced glucocorticoid negative feedback. On this background, concentrations of plasma corticosterone and adrenocorticotrophic hormone (ACTH) were elevated in unstressed mice, and showed a delayed return to baseline after stress in HSD1-null mice with reduced sensitivity to exogenous glucocorticoid feedback compared to same-background genetic controls. In the present study, we report that the genetic background can dramatically alter this pattern. By contrast to HSD1,/, mice on a 129/MF1 background, HSD1,/, mice congenic on a C57Bl/6J background have normal basal plasma corticosterone and ACTH concentrations and exhibit normal return to baseline of plasma corticosterone and ACTH concentrations after stress. Furthermore, in contrast to 129/MF1 HSD1,/, mice, C57Bl/6J HSD1,/, mice have increased glucocorticoid receptor expression in areas of the brain involved in glucocorticoid negative feedback (hippocampus and paraventricular nucleus), suggesting this may be a compensatory response to normalise feedback control of the HPA axis. In support of this hypothesis, C57Bl/6J HSD1,/, mice show increased sensitivity to dexamethasone-mediated suppression of peak corticosterone. Thus, although 11,-HSD1 appears to contribute to regulation of the HPA axis, the genetic background is crucial in governing the response to (and hence the consequences of) its loss. Similar variations in plasticity may underpin inter-individual differences in vulnerability to disorders associated with HPA axis dysregulation. They also indicate that 11,-HSD1 inhibition does not inevitably activate the HPA axis. [source] Temporal responses in the disruption of iron regulation by manganeseJOURNAL OF NEUROSCIENCE RESEARCH, Issue 8 2006Catherine Kwik-Uribe Abstract Manganese (Mn) is an essential trace element, though at elevated exposures it is also a neurotoxicant. Several mechanisms underlying manganese toxicity have been investigated, although a consistent mechanism(s) of action at low exposures has not been fully elucidated. Here we systematically evaluated the effects of in vitro manganese exposure on intracellular iron (Fe) homeostasis and iron-regulatory protein (IRP) binding activity in undifferentiated PC12 cells over a range of manganese exposure concentrations (1, 10, 50, and 200 ,M MnCl2) and exposure durations (12, 24, 36, and 48 hr), to test the hypothesis that moderately elevated manganese exposure disrupts cellular iron regulation. Results demonstrate that manganese exposure produces a rapid and sustained dose-dependent dysregulation of cellular iron metabolism, with effects occurring as early as 12 hr exposure and at manganese doses as low as 1 ,M. Manganese exposure altered the dynamics of IRP-1 binding and the intracellular abundance of IRP-2, and altered the cellular abundance of transferrin receptor, ferritin, and mitochondrial aconitase protein levels. Cellular levels of labile iron were significantly increased with manganese exposure, although total cellular iron levels were not. The overall pattern of effects shows that manganese produced an inappropriate cellular response akin to iron deficiency, to which the cells were able to mount a compensatory response. Consistent with our previous studies, these data indicate that even low to moderate exposures to Manganese in vitro significantly disrupt cellular iron metabolism, which may be an important contributory mechanism of manganese neurotoxicity. © 2006 Wiley-Liss, Inc. [source] Determining the contribution of asphyxia to brain damage in the neonateJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 4 2004James A. Low Abstract Studies in the research laboratory have demonstrated the complex relationship between fetal and newborn asphyxia and brain damage, a balance between the degree, duration and nature of the asphyxia and the quality of the cardiovascular compensatory response. Clinical studies would support the contention that the human fetus and newborn behave in a similar manner. An accurate diagnosis of asphyxia requires a blood gas and acid base assessment. The clinical classification of fetal asphyxia is based on a measure of metabolic acidosis to confirm that fetal asphyxia has occurred and the expression of neonatal encephalopathy and other organ system complications to express the severity of the asphyxia. The prevalence of fetal asphyxia at delivery is at term, 25 per 1000 live births of whom 15% are moderate or severe; and in the preterm, 73 per 1000 live births of whom 50% are moderate or severe. It remains to be determined how often the asphyxia recognized at delivery may have been present before the onset of labor. There is a growing body of indirect and direct evidence to support the contention that antepartum fetal asphyxia is important in the occurrence of brain damage. Although much of the brain damage observed in the newborn reflects events that occurred before delivery, newborn asphyxia and hypotension, particularly in the preterm newborn, may contribute to the brain damage accounting for deficits in surviving children [source] Melatonin reduces the neuronal loss, downregulation of dopamine transporter, and upregulation of D2 receptor in rotenone-induced parkinsonian ratsJOURNAL OF PINEAL RESEARCH, Issue 2 2008Chun-Hung Lin Abstract:, Parkinson's disease (PD) is a movement disorder resulting from nigrostriatal dopaminergic neurodegeneration. The impairment of mitochondrial function and dopamine synaptic transmission are involved in the pathogenesis of PD. Two mitochondrial inhibitors, 1-methyl-4-phenylpyridine (MPP+) and rotenone, have been used to induce dopaminergic neuronal death both in in vitro and in vivo models of PD. Because the uptake of MPP+ is mediated by the dopamine transporter (DAT), we used a cell-permeable rotenone-induced PD model to investigate the role of DAT and dopamine D2 receptor (D2R) on dopaminergic neuronal loss. Rotenone subcutaneously infused for 14 days induced PD symptoms in rats, as indicated by reduced spontaneous locomotor activity (hypokinesis), loss of tyrosine hydroxylase (TH, a marker enzyme for dopamine neurons) immunoreactivity in the substantia nigra and striatum, obvious ,-synuclein accumulation, downregulated DAT protein expression, and upregulated D2R expression. Interestingly, rotenone also caused significant noradrenergic neuronal loss in the locus coeruleus. Melatonin, an antioxidant, prevented nigrostriatal neurodegeneration and ,-synuclein aggregation without affecting the rotenone-induced weight loss and hypokinesis. However, rotenone-induced hypokinesis was markedly reversed by the DAT antagonist nomifensine and body weight loss was attenuated by the D2R antagonist sulpiride. In addition, both antagonists significantly prevented the reduction of striatal TH or DAT immunoreactivity but not the loss of nigral TH- and DAT-immunopositive neurons. These results suggested that oxidative stress and DAT downregulation are involved in the rotenone-induced pathogenesis of nigrostriatal dopaminergic neurodegeneration, whereas D2R upregulation may simply represent a compensatory response. [source] A competitive marathon race decreases neutrophil functions in athletesLUMINESCENCE: THE JOURNAL OF BIOLOGICAL AND CHEMICAL LUMINESCENCE, Issue 6 2003Daisuke Chinda Abstract A full marathon is the longest running race in official track events and is a form of acute exercise. However, no studies have examined the acute neutrophil function response to a competitive marathon race. Thirty-six male athletes who had just completed the 42.195 km course of the 50th Beppu-Oita Mainichi Marathon were enrolled in this study. Neutrophil oxidative burst activity, phagocytic activity and expression of CD11b and CD16 per cell were measured by flow cytometry immediately before and after the marathon. Total leukocyte/neutrophil counts increased significantly (p < 0.001), whereas total oxidative burst activity per neutrophil cell decreased significantly after the race (p < 0.001). Furthermore, total phagocytic activity per neutrophil cell also decreased after the race, although it was not significant (p = 0.08). Although CD11b expression per cell did not change, the expression of CD16 per cell significantly decreased (p < 0.001) after the race. In conclusion, a competitive marathon race decreased neutrophil functions (oxidative burst activity and phagocytic activity), which may be partly due to a decrease in CD16 expression. The increase in total neutrophil counts might reflect a compensatory response to counteract the decrease in neutrophil functions. Copyright © 2003 John Wiley & Sons, Ltd. [source] Comparative proteomic and transcriptional profiling of a bread wheat cultivar and its derived transgenic line overexpressing a low molecular weight glutenin subunit gene in the endospermPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 14 2008Federico Scossa Abstract We carried out a parallel transcriptional and proteomic comparison of seeds from a transformed bread wheat line that overexpresses a transgenic low molecular weight glutenin subunit gene relative to the corresponding nontransformed genotype. Proteomic analyses showed that, during seed development, several classes of endosperm proteins were differentially accumulated in the transformed endosperm. As a result of the strong increase in the amount of the transgenic protein, the endogenous glutenin subunit, all subclasses of gliadins, and metabolic as well as chloroform/methanol soluble proteins were diminished in the transgenic genotype. The differential accumulation detected by proteomic analyses, both in mature and developing seeds, was paralleled by the corresponding changes in transcript levels detected by microarray experiments. Our results suggest that the most evident effect of the strong overexpression of the transgenic glutenin gene consists in a global compensatory response involving a significant decrease in the amounts of polypeptides belonging to the prolamin superfamily. It is likely that such compensation is a consequence of the diversion of amino acid reserves and translation machinery to the synthesis of the transgenic glutenin subunit. [source] Medial temporal lobe function and structure in mild cognitive impairmentANNALS OF NEUROLOGY, Issue 1 2004Bradford C. Dickerson MD Functional magnetic resonance imaging (fMRI) was used to study memory-associated activation of medial temporal lobe (MTL) regions in 32 nondemented elderly individuals with mild cognitive impairment (MCI). Subjects performed a visual encoding task during fMRI scanning and were tested for recognition of stimuli afterward. MTL regions of interest were identified from each individual's structural MRI, and activation was quantified within each region. Greater extent of activation within the hippocampal formation and parahippocampal gyrus (PHG) was correlated with better memory performance. There was, however, a paradoxical relationship between extent of activation and clinical status at both baseline and follow-up evaluations. Subjects with greater clinical impairment, based on the Clinical Dementia Rating Sum of Boxes, recruited a larger extent of the right PHG during encoding, even after accounting for atrophy. Moreover, those who subsequently declined over the 2.5 years of clinical follow-up (44% of the subjects) activated a significantly greater extent of the right PHG during encoding, despite equivalent memory performance. We hypothesize that increased activation in MTL regions reflects a compensatory response to accumulating AD pathology and may serve as a marker for impending clinical decline. Ann Neurol 2004;56:27,35 [source] short report: High levels of serum angiogenic growth factors in patients with AL amyloidosis: comparisons with normal individuals and multiple myeloma patientsBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2010Efstathios Kastritis Summary Serum levels of five angiogenic cytokines were evaluated in 82 patients with primary systemic amyloidosis (AL). Angiopoietin-1, vascular endothelial growth factor, basic fibroblast growth factor and angiogenin were higher in AL patients than in controls (n = 35) and newly-diagnosed, symptomatic, myeloma patients (n = 35). Angiopoetin-1/Angiopoetin-2 ratio was lower in AL compared to controls but higher than in myeloma patients. Angiopoetin-2 correlated with cardiac dysfunction indices; however, none of the angiogenic growth factors was prognostically significant. The increased angiogenic cytokine levels observed in AL seem to represent either a toxic effect of amyloid fibrils or light chains, or a compensatory response to organ dysfunction. [source] MODULATION OF SIGNAL TRANSDUCERS AND ACTIVATORS OF TRANSCRIPTION (STAT) FACTOR PATHWAYS DURING FOCAL CEREBRAL ISCHAEMIA: A GENE EXPRESSION ARRAY STUDY IN RAT HIPPOCAMPUS AFTER MIDDLE CEREBRAL ARTERY OCCLUSIONCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2007Sheng-Li Sun SUMMARY 1Signal transducers and activators of transcription (STAT) factors are a family of transcription factors that mediate intracellular signalling initiated at cytokine cell surface receptors and transmitted to the nucleus. In the present study, we determined the global changes in STAT gene expression in the hippocampus of rats after focal cerebral ischaemia and reperfusion using microarray analysis. 2The present study used middle cerebral artery occlusion (MCAO) to induce ischaemia and reperfusion in Sprague-Dawley rats. Using superarray Q series Janus tyrosine kinases (Jak)/STAT signalling pathway gene array, a total of 96 genes was screened in adult male rat hippocampus after transient focal cerebral ischaemia. 3The results showed that 23 genes were upregulated at least twofold by ischaemia treatment and that 12 genes were downregulated at least threefold by ischaemia treatment compared with controls. 4After confirmation by quantitative real-time polymerase chain reaction, the data suggest that the gene expression of STAT2, 5a, 5b, 6 and suppressor of cytokine signalling (SOCS) 4 was increased by ischaemia, probably due to a compensatory response of the brain, which may play a protective role in damaged brain tissue. 5The results of the present study provide evidence on global changes in STAT gene expression in the hippocampus of rats after focal cerebral ischaemia and reperfusion, in which STAT2, 5a, 5b, 6 and SOCS4 were confirmed to be significantly modulated during focal cerebral ischaemia. [source] Indomethacin decreases particulate guanylyl cyclase activity in rat kidneyCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2004JongUn Lee SUMMARY 1.,Effects of non-steroidal anti-inflammatory drugs on the local atrial natriuretic peptide (ANP) and nitric oxide (NO) systems in the kidney were investigated. 2.,Male Sprague-Dawley rats were treated with indomethacin (5 mg/kg, every 12 h, i.p.) for 2 days. The expression of ANP and natriuretic peptide receptor-A (NPR-A) mRNA was determined in the kidney, as was that of endothelial NO synthase (NOS) proteins. Particulate and soluble guanylyl cyclase activities were determined separately. 3.,Following treatment with indomethacin, urinary sodium excretion decreased significantly. Although the renal expression of ANP was not changed significantly, that of NPR-A decreased significantly. The expression of NOS increased significantly. Particulate guanylyl cyclase activity was decreased, whereas the activity of soluble guanylyl cyclase was increased. The catalytic activity of Na+/K+ -ATPase was increased, with no significant changes in its expression. The expression of the type 3 Na/H exchanger and Na,K,2CL cotransporters increased significantly. 4.,The indomethacin-induced decrease in urinary sodium excretion may be attributed, at least in part, to decreased activity of the local ANP/cGMP system. The increased activity of the NO/cGMP system may be a compensatory response to the diminished activity of the prostaglandin system. [source] Mechanisms of genioglossus responses to inspiratory resistive load in rabbitsACTA PHYSIOLOGICA, Issue 3 2002N. P. ALEKSANDROVA ABSTRACT The purpose of the present study has been to determine whether pharyngeal dilator muscles participate in inspiratory load compensatory responses and if so, to elucidate role of upper airway mechanoreceptors in these responses. The experiments were performed on anaesthetized rabbits. Each animal was tested in three ways by the imposition of inspiratory resistive load: (1) at upper airways via face mask, (2) at the tracheostomic cannula placed below larynx (all upper airway receptors were `bypassed') and (3) at the mouth after the section of the hypoglossus nerves (motor denervation of genioglossus muscle). The inspiratory load applied to the upper airways evoked significant increases in integrated genioglossus activity (to 129 ± 14.7% of control) and its inspiratory duration (to 113 ± 5% of control) already within the first loaded breath (P < 0.05). The increases in the inspiratory activity of musculius genioglossus were relatively greater than the simultaneous increases in the activity of the diaphragm. Motor denervation of the pharynx dilator muscles (including m. genioglossus) increased airway resistance to 184 ± 19% of control (P < 0.05) and induced obstructive alterations in the breathing pattern during unloaded breathing: decrease in maximal inspiratory flow (,13%) and increase in the level of negative oesophageal pressure (+14%) and the peak diaphragm activity (+6%). After nervi hypoglossus sections additional increases in motor and pressure outputs were required in order to maintain unaltered ventilation at the same degree of loading as before denervation. The results indicate that the pharyngeal dilator muscles have a role in compensation of added inspiratory load. Activation of these muscles facilitate the load compensating function of `pump' muscles by decreasing airway resistance. Tracheostomy did not reduce the genioglossus response to inspiratory loading, ruling out any role for upper airways receptors in the genioglossus response to inspiratory load compensations. [source] Free fatty acids as mediators of adaptive compensatory responses to insulin resistance in dexamethasone-treated ratsDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2008Michela Novelli Abstract Background Chronic low-dose dexamethasone (DEX) treatment in rats is associated to insulin resistance with compensatory hyperinsulinaemia and reduction in food intake. We tested the hypothesis that the elevation in circulating free fatty acids (FFAs) induced by DEX is the common mediator of both insulin resistance and insulin hyperproduction. Methods For this purpose, an anti-lipolytic agent was administered during DEX treatment to lower lipacidaemia for several hours prior to glucose and insulin tolerance tests. Leptin expression in adipose tissue (by Northern blot) and plasma leptin levels (by radioimmunoassay) were also investigated to verify whether a rise in circulating leptin could be responsible for the anorectic effect of DEX. Results Our data show that a transient pharmacological reduction of elevated plasma FFA levels abates the post-loading hyperinsulinaemia and counteracts the insulin resistance induced by DEX, supporting the hypothesis that the chronic elevation in FFAs is the common mediator of DEX-induced changes. Despite enhanced leptin expression in white adipose tissue, DEX-treated rats show no significant increase in plasma leptin levels. This suggests that the anorectic effect of DEX should be mediated, at least partially, by other factors, possibly related to the influence of concomitantly elevated plasma FFA and insulin levels on the hypothalamic centers regulating feeding. Conclusions Our results sustain the idea that a prolonged increase in plasma FFA levels plays an important role in the adaptive regulation of glucose and energy homeostasis, not only by potentiating insulin secretion but also by providing a signal of ,nutrient abundance' capable of restraining food intake. Copyright © 2007 John Wiley & Sons, Ltd. [source] Development, growth, and egg production of Ageneotettix deorum (Orthoptera: Acrididae) in response to spider predation risk and elevated resource qualityECOLOGICAL ENTOMOLOGY, Issue 1 2004Bradford. Abstract., 1.,Predation risk to insects is often size- or stage-selective and usually decreases as prey grow. Any factor, such as food quality, that accelerates developmental and growth rates is likely to reduce the period over which prey are susceptible to size-dependent predation. 2.,Using field experiments, several hypotheses that assess growth, development, and egg production rates of the rangeland grasshopper Ageneotettix deorum (Scudder) were tested in response to combinations of food quality and predation risk from wolf spiders to investigate performance variation manifested through a behaviourally mediated path affecting food ingestion rates. 3.,Grasshoppers with nutritionally superior food completed development , 8,18% faster and grew 15,45% larger in the absence of spiders, in comparison with those subjected to low quality food exposed to spider predators. Growth and development did not differ for grasshoppers feeding on high quality food when predators were present in comparison with lower quality food unimpeded by predators. Responses indicated a compensatory relationship between resource quality and predation risk. 4.,Surviving grasshoppers produced fewer eggs compared with individuals not exposed to spiders. Because no differences were found in daily egg production rate regardless of predation treatment, lower egg production was attributed to delayed age of first reproduction. Results compare favourably with responses observed in natural populations. 5.,Risk of predation from spiders greatly reduced growth, development, and ultimately egg production. Increased food quality counteracts the impact of predation risk on grasshoppers through compensatory responses, suggesting that bottom-up factors mediate effects of spiders. [source] Effects of a toxicant on population growth rates: sublethal and delayed responses in blowfly populationsFUNCTIONAL ECOLOGY, Issue 6 2001S. J. MOE Summary 1,Previous studies have shown that cadmium exposure of blowfly populations (Lucilia sericata[Meigen 1826]) results in reduced population growth rate, but also in higher individual mass, because of reduced competition for food. In this study, the discrepancy between the positive effect on individual growth and the negative effect on population growth is investigated, by measuring direct and delayed effects of cadmium in the adult stage. 2,Blowfly populations were exposed to cadmium through the diet in four treatment combinations: larval stage, adult stage, both stages or neither stage. The effects on accumulation of cadmium, survival, development time, mass and reproductive rate were measured. 3,Cadmium was accumulated from both stages. 4,Individuals exposed to cadmium in the larval stage had higher mean pupal and adult mass (because of reduced densities), but also reduced adult longevity and fecundity. 5,Adult longevity and fecundity were also reduced by cadmium exposure in the adult stage. 6,In stage-structured populations, the link between individual-level and population-level responses to a toxicant may be complicated by stage-specific sensitivities to the toxicant, by delayed responses in the adult stage to sublethal effects in the juvenile stage, and by density-dependent compensatory responses to toxicant-induced mortality. [source] Combined therapy in the treatment of hypertensionFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2010Carlos Escobar Abstract The majority of patients with hypertension need at least two antihypertensive agents to achieve blood pressure (BP) objectives. As current European guidelines for the treatment of arterial hypertension recommend, combined therapy is required when monotherapy fails and as a first-line treatment in certain situations, such as subjects at high or very high cardiovascular risk, markedly elevated BP values, or when lower targets are required (<130/80 mmHg). The advantages of combined therapy are well known and include an earlier and higher antihypertensive efficacy because of complementary mechanisms of action, and a lower incidence of side effects due to the possible compensatory responses and, in many cases, the lower doses used. In the present study, available evidence about the efficacy and tolerability of combined therapy for the treatment of hypertension is updated. [source] Population dynamics of fisheries stock enhancementJOURNAL OF FISH BIOLOGY, Issue 2004K. Lorenzen The population dynamics of fisheries stock enhancement, and its potential for generating benefits over and above those obtainable from optimal exploitation of wild stocks alone are poorly understood and highly controversial. I extend the dynamic pool theory of fishing to stock enhancement by unpacking recruitment, incorporating regulation in the recruited stock, and accounting for biological differences between wild and hatchery fish. I then analyse the dynamics of stock enhancement and its potential role in fisheries management, using the candidate stock of North Sea sole as an example. Enhancement through release of recruits or advanced juveniles is predicted to increase total yield and stock abundance, but reduce abundance of the naturally recruited stock component through compensatory responses or overfishing. Release of genetically maladapted fish reduces the effectiveness of enhancement, and is most detrimental overall if fitness of hatchery fish is only moderately compromised. As a temporary measure for rebuilding of depleted stocks, enhancement can not substitute for effort limitation, and is advantageous as an auxiliary measure only if the population has been reduced to a very low proportion of its unexploited biomass. Quantitative analysis of population dynamics is central to the responsible use of stock enhancement in fisheries management, and the necessary tools are available. [source] Striatal susceptibility to a dopaminergic neurotoxin is independent of sex hormone effects on cell survival and DAT expression but is exacerbated by central aromatase inhibitionJOURNAL OF NEUROCHEMISTRY, Issue 3 2007Simon McArthur Abstract The aim of this study was to investigate further the hormone-dependent processes underlying sex differences in neurotoxic responses within the rat nigrostriatal dopaminergic (NSDA) pathway after partial lesioning with 6-OHDA, a state thought to mimic the early stages of Parkinson's disease where, in humans and animal models alike, males appear to be more susceptible. Contrary to our hypotheses, hormone manipulations (gonadectomy ± oestrogen or androgen treatment) failed to alter survival of tyrosine hydroxylase immunoreactive cells in the substantia nigra pars compacta (SNc) after lesioning; this indicates that, unlike inherent sex differences in toxin-induced striatal dopamine depletion, sex differences in cell loss were not hormonally generated, and that hormone-dependent changes in dopamine depletion can occur independently of cell survival. In addition, hormonally induced changes in striatal expression of the dopamine transporter (DAT), an important factor for 6-OHDA toxicity, did not correlate with hormonal influences on striatal dopamine loss and, in males, central inhibition of aromatase prior to 6-OHDA infusion exacerbated striatal dopamine loss with no effect on SNc tyrosine hydroxylase-immunoreactive survival, suggesting locally generated oestrogen is neuroprotective. These results support the novel view that sex steroid hormones produced peripherally and centrally play a significant, sex-specific role within the sexually dimorphic NSDA pathway to modulate plastic, compensatory responses aimed at restoring striatal dopamine functionality, without affecting cell loss. [source] Size compensation in moth larvae: attention to larval instarsPHYSIOLOGICAL ENTOMOLOGY, Issue 3 2010TOOMAS ESPERK Environmental perturbations such as starvation and poor diet often prevent animals from attaining their optimal sizes. When the perturbation has a transient character, compensatory responses are expected in terms of faster growth or a prolonged developmental period. In the case of insect larvae, details of such responses are insufficiently known at the proximate level. Attention to responses at the level of particular larval instars should promote an understanding of insect developmental plasticity also in a more general context. To provide an instar-specific analysis of compensatory growth, larvae of the moth Orgyia antiqua (L.) are reared on inferior diet during one larval instar. Responses in growth parameters are recorded in the course of the manipulated instars, as well as at the level of the entire larval period. The negative relationship between development time and size in response to the inferior food quality, typical of the entire larval periods, is also observed within the manipulated instars taken separately. The manipulated larvae remain smaller than the larvae of the control group (significant in males only), even by the end of the subsequent instar during which all individuals are provided with superior host. In males, close to full size compensation by the time of pupation is achieved only by means of adding an extra larval instar. The inability of larvae to fully compensate during one and even two instars is considered as an indication of the presence of constraints on the within-instar growth pattern. An alternative, adaptational explanation for the incomplete compensation could be based on the cost of prolonged development period. Given the ecological context of the species' life history, such an explanation appears less likely. [source] Peroxiredoxin Q of Arabidopsis thaliana is attached to the thylakoids and functions in context of photosynthesis,THE PLANT JOURNAL, Issue 6 2006Petra Lamkemeyer Summary Peroxiredoxin Q (Prx Q) is one out of 10 peroxiredoxins encoded in the genome of Arabidopsis thaliana, and one out of four that are targeted to plastids. Peroxiredoxin Q functions as a monomeric protein and represents about 0.3% of chloroplast proteins. It attaches to the thylakoid membrane and is detected in preparations enriched in photosystem II complexes. Peroxiredoxin Q decomposes peroxides using thioredoxin as an electron donor with a substrate preference of H2O2 > cumene hydroperoxide , butyl hydroperoxide , linoleoyl hydroperoxide and insignificant affinity towards complex phospholipid hydroperoxide. Plants with decreased levels of Prx Q did not have an apparently different phenotype from wildtype at the plant level. However, similar to antisense 2-cysteine (2-Cys) Prx plants [Baier, M. et al. (2000)Plant Physiol., 124, 823,832], Prx Q-deficient plants had a decreased sensitivity to oxidants in a leaf slice test as indicated by chlorophyll a fluorescence measurements. Increased fluorescence ratios of photosystem II to I at 77 K and modified transcript levels of plastid- and nuclear-encoded proteins show that regulatory mechanisms are at work to compensate for the lack of Prx Q. Apparently Prx Q attaches to photosystem II and has a specific function distinct from 2-Cys peroxiredoxin in protecting photosynthesis. Its absence causes metabolic changes that are sensed and trigger appropriate compensatory responses. [source] Weight gain and lipid deposition in Atlantic salmon, Salmo salar, during compensatory growth: evidence for lipostatic regulation?AQUACULTURE RESEARCH, Issue 12 2001S J S Johansen Abstract Feed-restricted fish gain less body mass and storage reserves than well-fed fish, and reduced rates of gain often trigger compensatory responses, characterized by increased appetite (hyperphagia) and growth rate. The results of previous investigations have introduced a hypothesis in which adipose tissue (fat stores) had a regulatory role in governing appetite. An extension of this suggests that hyperphagia may relate to the severity of the feed restriction, and that the compensatory responses will cease once fat reserves are restored relative to body size. This was tested in two trials in which feed-restricted or -deprived postsmolt Atlantic salmon, Salmo salar, became hyperphagic after transfer to excess feeding. At the end of the first trial, previously feed-restricted fish had fully compensated for their lost weight gain compared to continuously fed control fish, but had a leaner body composition (i.e. reduced energy stores) and were still showing signs of compensatory growth. In the second trial, feed deprivation drained body lipids and caused a stronger hyperphagic response than restrictive feeding, although it took longer to develop. Feed intake became coincident when fish had a similar body composition for size, but this occurred at different times. Hence, the fish that had been deprived of feed were smaller than the restricted fish at the end of the trial. The results of the present study demonstrate a link between the magnitude of lipid stores, feed intake and weight gain, and provide some evidence for lipostatic appetite regulation in fish. [source] Counteractive biomass allocation responses to drought and damage in the perennial herb Convolvulus demissusAUSTRAL ECOLOGY, Issue 5 2010IVÁN M. QUEZADA Abstract Herbivory and water shortage are key ecological factors affecting plant performance. While plant compensatory responses to herbivory include reallocation of biomass from below-ground to above-ground structures, plant responses to reduced soil moisture involve increased biomass allocation to roots and a reduction in the number and size of leaves. In a greenhouse study we evaluated the effects of experimental drought and leaf damage on biomass allocation in Convolvulus demissus (Convolvulaceae), a perennial herb distributed in central Chile, where it experiences summer drought typical of Mediterranean ecosystems and defoliation by leaf beetles and livestock. The number of leaves and internode length were unaffected by the experimental treatments. The rest of plant traits showed interaction of effects. We detected that drought counteracted some plant responses to damage. Thus, only in the control watering environment was it observed that damaged plants produced more stems, even after correcting for main stem length (index of architecture). In the cases of shoot : root ratio, relative shoot biomass and relative root biomass we found that the damage treatment counteracted plant responses to drought. Thus, while undamaged plants under water shortage showed a significant increase in root relative biomass and a significant reduction in both shoot : root ratio and relative shoot biomass, none of these responses to drought was observed in damaged plants. Total plant biomass increased in response to simulated herbivory, apparently due to greater shoot size, and in response to drought, presumably due to greater root size. However, damaged plants under experimental drought had the same total biomass as control plants. Overall, our results showed counteractive biomass allocation responses to drought and damage in C. demissus. Further research must address the fitness consequences under field conditions of the patterns found. This would be of particular importance because both current and expected climatic trends for central Chile indicate increased aridity. [source] Panic disorder: from respiration to the homeostatic brainACTA NEUROPSYCHIATRICA, Issue 2 2004Giampaolo Perna There is some experimental evidence to support the existence of a connection between panic and respiration. However, only recent studies investigating the complexity of respiratory physiology have revealed consistent irregularities in respiratory pattern, suggesting that these abnormalities might be a vulnerability factor to panic attacks. The source of the high irregularity observed, together with unpleasant respiratory sensations in patients with panic disorder (PD), is still unclear and different underlying mechanisms might be hypothesized. It could be the result of compensatory responses to abnormal respiratory inputs or an intrinsic deranged activity in the brainstem network shaping the respiratory rhythm. Moreover, since basic physiological functions in the organism are strictly interrelated, with reciprocal modulations and abnormalities in cardiac and balance system function having been described in PD, the respiratory findings might arise from perturbations of these other basic systems or a more general dysfunction of the homeostatic brain. Phylogenetically ancient brain circuits process physiological perceptions/sensations linked to homeostatic functions, such as respiration, and the parabrachial nucleus might filter and integrate interoceptive information from the basic homeostatic functions. These physiological processes take place continuously and subconsciously and only occasionally do they pervade the conscious awareness as ,primal emotions'. Panic attacks could be the expression of primal emotion arising from an abnormal modulation of the respiratory/homeostatic functions. [source] | |||||||||||||||||||||||||||||||