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At least 397 records · Page 22Linked to original sources

PubMed2004

Serum cholestenoic acid as a potential marker of pulmonary cholesterol homeostasis: increased levels in patients with pulmonary alveolar proteinosis.

The conversion of cholesterol into the more polar metabolites 27-hydroxycholesterol (27-OH) and cholestenoic acid by the cytochrome P450 sterol 27-hydroxylase is a cholesterol-removal mechanism used by almost all cells. Most of the cholestenoic acid present in the circulation originates from the lung, and it has been suggested that sterol 27-hydroxylase is of particular importance for cholesterol homeostasis in this organ. As an example of pulmonary cholesterol accumulation, a known disorder of surfactant homeostasis, pulmonary alveolar proteinosis (PAP), was studied. Analysis of bronchoalveolar lavage fluid from PAP patients revealed a significant accumulation of the cholesterol metabolites cholestenoic acid and 27-OH. This pattern was recapitulated in serum, with a significant increase in the levels of both cholestenoic acid (P=0.003) and 27-OH (P=0.017) in PAP patients compared with healthy controls. Analysis of PAP alveolar macrophages did not reveal a significant change in mRNA expression levels of either sterol 27-hydroxylase or the cholesterol-esterifying enzyme acyl-CoA:cholesterol acyltransferase-1. These results are consistent with the contention that substrate availability, rather than enzyme expression, is the key factor in regulating the production of cholestenoic acid by the lung and that serum cholestenoic acid may be a marker of pulmonary cholesterol homeostasis.

Adult↗

PubMed1994

The role of monovalent cation/proton antiporters in Na(+)-resistance and pH homeostasis in Bacillus: an alkaliphile versus a neutralophile.

Both neutralophilic Bacillus subtilis and alkaliphilic Bacillus firmus OF4 depend upon electrogenic Na+/H+ antiporters, which are energized by the gradients established by respiration-coupled proton extrusion, to achieve Na(+)-resistance and pH homeostasis when the external pH is very alkaline. The interplay of proton and sodium cycles is discussed. In B. subtilis, pH homeostasis, up to pH9, can be achieved using K+ when Na+ is unavailable or when the gene encoding the Na+/H+ antiporter that is involved in Na(+)-dependent pH homeostasis is disrupted. That gene is a member of the tetracycline efflux family of genes. A second gene, encoding a Na+/H+ antiporter that functions in Na(+)-resistance, has been identified, and candidates for the K+/H+ antiporter genes are under investigation. Aggregate Na+/H+ antiport activity in B. subtilis is as much as 10 times lower than in the alkaliphile, and the neutralophile cannot regulate its internal pH upon a shift to pH 10.5. Upon such a shift, there is a pronounced reduction in the generation of a primary electrochemical proton gradient. The alkaliphile, by contrast, maintains substantial driving forces and regulates its internal pH in an exclusively Na(+)-coupled manner upon shifts to either pH 8.7 or 10.5. One gene locus has been identified and a second locus has been inferred as encoding relevant antiporter activities.

Antiporters↗

PubMed2006

Copper in medicine: homeostasis, chelation therapy and antitumor drug design.

As one of the most important essential transition metals, copper is involved in a variety of biological processes such as embryo development, connective tissue formation, temperature control and nerve cell function. It is also related to severe diseases such as Wilson's and Menkes diseases and some neurological disorders. Novel components of copper homeostasis include copper-transporting P-type ATPases, Menkes and Wilson proteins, and copper chaperones in humans have been identified and characterized at the molecular level. These findings have paved the way towards better understanding of the role of copper deficiency or copper toxicity in physiological and pathological conditions. Therefore, organic compounds that can interfere with copper homeostasis may find therapeutic application in copper-dependent diseases. The antitumor activity of copper complexes was reported several decades ago, and many new complexes have demonstrated great antitumor potential. Copper complexes may have relatively lower side effects than platinum-based drugs, and are suggested to be able to overcome inherited or acquired resistance of cisplatin. In this overview, the most recent advances in copper homeostasis, copper-related chelation therapy and design of copper-based antitumor complexes will be summarized.

Antineoplastic Agents↗

PubMed1982

Neurocybernetic control mechanisms of informational homeostasis.

This paper discusses the fact, that to be able to keep its stability in a very variable environment, alongside substantial and energetical exchanges, the human organism must maintain also a permanent informational exchange with the environment it lives in. But the communication functions of the organism are of a very limited volume and cannot transmit all the information offered by the environment. Therefore, the organism is obliged to perform a rigorous selection of information received. A first selection is performed by means of excitability threshold and of the refractory period. A more adequate selection is performed by means of inhibition, habituation, attention, tiredness, and sleep. But those mechanisms control only the signals, reception, because organism receive only some signals from the exterior. Those signals are information carriers. But, in order to be able to discover the information it carries, the nervous system must submit the received signals to some very complicated processings, as the superisation process is. Because the discovered information does not depend only on received signals, but also on the way they were processed; information discovered by the nervous system is not similar to that emitted by the source. Therefore, informational homeostasis is not similar to signal homeostasis. Along beside signals selecting means, for informational homeostasis preservation, there are also certain affective factors and especially the process of discovering and processing of discovered information. These mechanisms can assure neuropsychical equilibrium under overstressing and substressing informational condition. And their disturbance can lead to certain psychical diseases.

Animals↗

PubMed1996

Endocrine, renal, and circulatory influences on fluid and electrolyte homeostasis during weightlessness: a joint Russian-U.S. project.

Microgravity is known to have a substantial effect on fluid homeostasis. The research described here was planned as part of the first joint Russian-U.S. science program carried out during a Shuttle flight. The aim of the program was to study the nature of the changes in fluid homeostasis induced by microgravity, as well as to determine the possible mechanisms underlying the regulation of fluid balance under conditions of spaceflight. To determine the effects of spaceflight on the homeostasis of fluid and electrolytes, measurements were taken of total body water, extracellular fluid plasma volumes, levels of regulatory hormones, and nutrient consumption before, during, and after a nine-day flight. Changes in renal function were studied before and after the flight. In these 2 subjects, weightlessness was not associated with a decreased extracellular fluid volume. However, there were the characteristic decreases in plasma atrial natriuretic peptide concentrations, and increases in plasma and urinary cortisol. Results indicated decreased urine volume, even through the first 48 hours of flight. Fluid volumes and glomerular filtration rate were increased after landing, probably related to the saline-loading countermeasure used by Shuttle crewmembers. The information obtained as a result of this research will facilitate the development of future research programs, as well as preventive measures for future long-duration spaceflights.

Body Water↗

PubMed2004

[Ghrelin: a new peptide regulating the neurohormonal system and energy homeostasis].

Ghrelin: a new peptide regulating the neurohormonal system and energy homeostasis. Research leading to the identification of ghrelin started with the discovery of growth hormone secretagogues, continued with the description of ghrelin receptors and ended with description of the chemical structure of ghrelin. However, several aspects concerning the role of ghrelin in physiology and pathophysiology are still under investigation. The majority of ghrelin is produced in the stomach, but it is also expressed in the hypothalamus, pituitary, intestine, kidney, heart, pancreas and gonads. Ghrelin stimulates growth hormone secretion via growth hormone secretagogue receptors, and it increases appetite. Ghrelin secretion in the stomach depends on both acute and chronic changes in energy balance. Presently available data support the hypothesis that the stomach, in addition to its important role in digestion, not only influences pituitary hormone secretion via ghrelin production but it also sends orexigenic (appetite increasing) signals to hypothalamic nuclei involved in the regulation of energy homeostasis. In addition to these main effects, ghrelin influences the cardiovascular, gastrointestinal, reproductive and endocrine functions. It can be anticipated that further research on the physiological and pathophysiological role of ghrelin will lead to a better understanding of neurohormonal processes and the central regulation of energy homeostasis.

Animals↗

PubMed2026

CNNM2 in schizophrenia: multilevel evidence of genetic susceptibility, magnesium homeostasis, neurodevelopment and cognitive dysfunction.

Schizophrenia (SCZ) is a common psychiatric disorder with a complex, genetically and environmentally influenced etiology, but the specific pathogenesis remains unclear. In recent years, the SCZ susceptibility gene CNNM2 (encoding cyclin M2) located at the 10q24.32-33 locus has received widespread attention. The well-validated SCZ risk interval 10q24.32-33 harbors two independent risk variants: rs11191580 in NT5C2 (significantly associated with CNNM2 mRNA and protein levels) and rs7914558 in CNNM2. Results from functional genomic analyses indicate that lower CNNM2 expression is significantly associated with SCZ. Imaging genetics studies have demonstrated that carriers of risk alleles of CNNM2 SNPs exhibit alterations in brain structure. Animal model studies have revealed that Cnnm2 downregulation in mice leads to impairments in sensorimotor gating and cognitive function. As an Mg2+ transporter, CNNM2 primarily maintains systemic Mg2+ homeostasis. According to clinical studies, a proportion of patients with SCZ exhibit reduced Mg2+ concentrations in plasma and cerebrospinal fluid. CNNM2 dysfunction may contribute to the pathology of SCZ by disrupting Mg2+ homeostasis, thereby affecting neurodevelopment and synaptic plasticity. A systematic consolidation of current evidence supporting the involvement of CNNM2 in SCZ pathogenesis provides a direction for further investigation of the pathological mechanisms underlying this disease, and for identification of novel targets for clinical intervention..

Schizophrenia↗

PubMed1960

Relationship of stress-induced histidine decarboxylase to circulatory homeostasis and shock.

Histidine decarboxylase activity of mouse tissues is increased by stress and by injection of epinephrine and norepinephrine, suggesting a balance between histamine and catechol amines producing a component of circulatory homeostasis. Imbalance during intense stress might lead to failure of circulatory homeostasis and to shock. Reasons for discounting histamine as "shock toxin" may be invalid.

Amines↗

PubMed1997

TGF-beta1 prevents gp120-induced impairment of Ca2+ homeostasis and rescues cortical neurons from apoptotic death.

HIV-1 infection frequently induces neuronal death responsible for the development of neurological deficits associated with AIDS. Several reports suggest that gp120, the HIV-1 envelope glycoprotein, is the main candidate as mediator of the HIV-1-dependent neurotoxicity. Here we report the effect of gp120 on the survival of cortical neurons in vitro and the possible mechanisms whereby it occurs. Mature cortical neurons, cultured on a feeder layer of astrocytes, were treated with gp120 in a defined culture medium in absence of serum. The treatment with gp120 induced time-dependent neuronal damage displaying apoptotic features, as revealed by in situ labelling of DNA fragmentation. TGF-beta1, a cytokine that has been previously shown to exert neuroprotective effects, prevented the cell death induced by exposure of cortical neurons to gp120. The prolonged treatment with gp120 also increased neuronal [Ca2+]i, while the coincubation with TGF-beta1 completely prevented the impairment of neuronal Ca2+ homeostasis. These data, taken together, demonstrate that gp120 induces apoptosis in cortical neurons, an effect that can be related to the impairment of Ca2+ homeostasis, and that TGF-beta1 pretreatment reverts both the neuronal death and the alterations in neuronal [Ca2+]i.

Animals↗

PubMed1997

Abnormal calcium homeostasis in astrocytes from the trisomy 16 mouse.

The regulation of intracellular Ca2+ was investigated in cultured astrocytes from the trisomy 16 (Ts16) mouse, an animal model for Down syndrome and Alzheimer's disease (AD). The cytoplasmic ionized Ca2+ concentration ([Ca2+]cyt) was determined using digital imaging of fura-2-loaded cells. The relative Ca2+ content of internal endoplasmic reticulum (ER) stores was estimated from the magnitude of the transient increase in [Ca2+]cyt induced by cyclopiazonic acid (CPA), an inhibitor of Ca2+ sequestration into ER stores. At rest, the average [Ca2+]cyt was 140 nM in euploid (normal) astrocytes, but over twice as high, 320 nM, in Ts16 cells. In the absence of extracellular Ca2+, CPA induced a transient increase in [Ca2+]cyt to over 1200 nM in Ts16 astrocytes as compared to only 500 nM in euploid cells, indicating an increased amount of Ca2+ in the Ts16 astrocyte ER. In contrast to euploid astrocytes, both resting [Ca2+]cyt and the amount of Ca2+ in the ER stores varied widely among individual Ts16 astrocytes. These results show that Ts16 produces a dysregulation of Ca2+ homeostasis leading to increased cytoplasmic and stored Ca2+. Since increases in [Ca2+]cyt have been implicated in the etiology of neurodegenerative diseases, including AD, this finding of abnormal Ca2+ homeostasis in a genetic model of human neurological disorders suggests that Ca2+ dysregulation may be a common feature underlying neurodegenerative processes.

Alzheimer Disease↗

PubMed1999

Phosphate induced developmental arrest of hamster two-cell embryos is associated with disrupted ionic homeostasis.

Culture of hamster embryos with 0.35 mM inorganic phosphate results in developmental arrest at the 2-cell stage. These arrested 2-cell embryos were found to have significantly elevated levels of both intracellular pH and intracellular free calcium. Culture of 2-cell embryos with both glucose and phosphate did not further alter intracellular ionic homeostasis. Developmental arrest of 2-cell embryos was dependent on the concentration of phosphate used. Culture with 1.25 microM phosphate did not alter development, while concentrations of 2.5 microM and 5.0 microM resulted in a percentage of embryos arresting development at the 2-cell stage. Analysis of intracellular levels of pH and calcium after culture with different phosphate concentrations revealed a significant negative correlation between intracellular calcium levels and development beyond the 2-cell stage. There was no correlation between the increase in intracellular pH and embryo development in the presence of phosphate. The increase in intracellular calcium levels after culture with phosphate appears to be derived from intracellular pools, as preventing the influx of extracellular calcium did not alter development beyond the 2-cell stage. Therefore, it is apparent that a disruption in ionic homeostasis is associated with developmental arrest of hamster embryos cultured with phosphate.

Animals↗

PubMed2000

Calcium homeostasis in larval and adult Drosophila melanogaster.

Calcium homeostasis in Drosophila melanogaster was examined in response to the challenges imposed by growth, reproduction and variations in dietary calcium content. Turnover time for calcium, calculated as the time for (45)Ca(2+)to accumulate to half the steady state value of 3.46 nmol/fly, was 3.3 days. Although larvae weighed 2x as much as adults, they contained 3-4x as much calcium. Anterior Malpighian tubules (Mts) contain much more calcium than posterior Mts, accounting for 25-30% of the calcium content of the whole fly. In response to a 6.2-fold increase in dietary calcium level, calcium content of whole flies increased only 10%. Hemolymph calcium concentration ( approximately 0.5 mM) was similar in males and females and in animals raised on diets differing in calcium content. Fluid secretion rate, secreted fluid calcium concentration, and transepithelial calcium flux in tubules isolated from flies raised on high and low calcium diets did not differ significantly. Malpighian tubules secrete calcium at rates sufficient to eliminate whole body calcium content in 0.5 and 3 days for tubules secreting fluid at basal and maximal rates, respectively. It is suggested that flies absorb high quantities of calcium from the diet and maintain homeostasis through the combined effects of elimination of calcium in fluid secreted by the Malpighian tubules and the sequestration of calcium in granules, especially within the distal segment of the anterior pair of Malpighian tubules.

Animals↗

PubMed1980

Abnormalities in water homeostasis in small cell anaplastic lung cancer.

Forty-one patients with newly diagnosed small cell anaplastic lung cancer were evaluated for abnormalities in water homeostasis. Each patient underwent a standard water load (SWL) test. Overall, 68% had abnormalities in the SWL test. Abnormalities were found in 47% of the patients with carcinoma clinically limited to one hemithorax and in 86% of the patients with more extensive carcinoma. The determination of urinary antidiuretic hormone levels was available for 27 patients. Abnormally elevated levels were found in 44% of those patients. Forty-six patients had clinically detectable syndrome of the inappropriate secretion of antidiuretic hormone (SIADH); in 12% of patients water restriction was necessary. The incidence of detectable abnormalities in water homeostasis in this study was higher than has been previously recognized. The SWL test is a sensitive and useful means of determining the presence of impaired water handling in patients with small cell carcinoma of the lung.

Blood Urea Nitrogen↗

PubMed2000

Hyaluronan oligosaccharides perturb cartilage matrix homeostasis and induce chondrocytic chondrolysis.

OBJECTIVE: To determine the role of CD44-mediated matrix assembly in maintaining cartilage homeostasis. METHODS: Articular cartilage tissue slices as well as isolated chondrocytes were treated with hyaluronan (HA) hexasaccharides. Tissues and cells were processed for histology, immunohistochemistry, colorimetric assay, reverse transcriptase-polymerase chain reaction, and zymography. RESULTS: HA oligosaccharides induced a dose-dependent state of chondrocytic chondrolysis, including near-total loss of stainable proteoglycan-rich matrix, activation of gelatinolytic activity, and exhibition of the NITEGE epitope. However, HA oligosaccharides also induced an increase of proteoglycan synthesis, including elevation of aggrecan and HA synthase 2 messenger RNA. CONCLUSION: Uncoupling chondrocytes from the matrix results in deleterious changes in matrix structure and modifications in chondrocyte metabolism. The close interaction of chondrocytes with their matrix and their ability to "sense" changes in receptor occupancy are needed for maintenance of cartilage homeostasis.

Aggrecans↗

PubMed1999

The effects of transport perturbations on the homeostasis of erythrocytes.

The control of erythrocyte volume, pH, membrane potential and ion content results from the interaction of many passive and active transport systems, cytoplasmic buffers, and from the charge and osmotic properties of haemoglobin and other impermeant solutes. The complexity of the system is such that the understanding of cell responses to experimental, physiological and pathophysiological challenges is beyond intuitive grasp. Mathematical models of erythrocyte and reticulocyte homeostasis have delivered a wealth of novel and unexpected predictions that have been confirmed experimentally. Those concerning effects of Ca(2)+ and K+ permeabilization on cell volume, pH and osmolality have helped solve long-standing issues on the pathophysiology of sickle-cell dehydration and will be briefly reviewed here. To study the effects of parasite growth and of new permeation pathways (NPP) on host cell homeostasis, we have developed a model of a Plasmodium falciparum- infected erythrocyte. Modelling NPP to fit reported changes in both Na+/K+ fluxes and gradients predicted large variations in host cell haemoglobin concentration, [Hb]. However, preliminary estimates seem to indicate that host cell [Hb] is conserved throughout the parasite's asexual cycle, suggesting that the properties of the NPP vary in subtle, stage-dependent ways.

Animals↗

PubMed1986

The genetics of quantifiable homeostasis: I. The general issues.

Some fundamental issues in developing the quantitative genetics of heritable traits are addressed. Such a trait must be capable of being represented as a quantity. Choice of the metric can be satisfactorily made only in the light of some insight into the nature of the trait and what its revealing characteristics may be. This insight is likely to change as more is known about the process, so the form and detail of the analysis is not static but perhaps continually evolving. Much has been made out of sample means and, at a more sophisticated level, Galton-Fisher theory (the analysis of the first two moments of multivariate Gaussian variates). However, at least some processes seriously violate the assumptions underlying that theory. One such group comprises traits in which the means are unvarying and the genetic message lies in other aspects of the distribution; in these circumstances the standard summary statistics such as heritability, regression, and correlation may be totally uninformative, distracting, or even misleading. This paradox is illustrated by reference to homeostasis, where the Mendelian component lies, not in the mean, but in the degree of laxity of control. Since estimating higher moments is notoriously imprecise, the suggested remedy is the familial and commonsense one of exploring the genetics of the intermediate states and underlying mechanisms and not only that of the resultant ("bottom-line") phenotype. In our chosen problem, the task of relating the outcome to the basic mechanism of inheritance calls for a detailed understanding of the homeostasis involved.

Genetic Diseases, Inborn↗

PubMed2001

Low cerebrospinal fluid hypocretin (Orexin) and altered energy homeostasis in human narcolepsy.

Hypocretins (orexins) are hypothalamic neuropeptides involved in sleep and energy homeostasis. Hypocretin mutations produce narcolepsy in animal models. In humans, narcolepsy is rarely due to hypocretin mutations, but this system is deficient in the cerebrospinal fluid (CSF) and brain of a small number of patients. A recent study also indicates increased body mass index (BMI) in narcolepsy. The sensitivity of low CSF hypocretin was examined in 38 successive narcolepsy-cataplexy cases [36 human leukocyte antigen (HLA)-DQB1*0602-positive] and 34 matched controls (15 controls and 19 neurological patients). BMI and CSF leptin levels were also measured. Hypocretin-1 was measurable (169 to 376 pg/ml) in all controls. Levels were unaffected by freezing/thawing or prolonged storage and did not display any concentration gradient. Hypocretin-1 was dramatically decreased (<100 pg/ml) in 32 of 38 patients (all HLA-positive). Four patients had normal levels (2 HLA-negative). Two HLA-positive patients had high levels (609 and 637 pg/ml). CSF leptin and adjusted BMI were significantly higher in patients versus controls. We conclude that the hypocretin ligand is deficient in most cases of human narcolepsy, providing possible diagnostic applications. Increased BMI and leptin indicate altered energy homeostasis. Sleep and energy metabolism are likely to be functionally connected through the hypocretin system.

Adolescent↗

PubMed2003

Insulin-like growth factor 1-induced interleukin-1 receptor II overrides the activity of interleukin-1 and controls the homeostasis of the extracellular matrix of cartilage.

OBJECTIVE: We examined the effect of the insulin-like growth factor 1 (IGF-1)/IGF receptor I (IGFRI) autocrine/paracrine anabolic pathway on the extracellular matrix (ECM) of human chondrocytes and the mechanism by which IGF-1 reverses the catabolic effects of interleukin-1 (IL-1). METHODS: Phenotypically stable human articular cartilage cells were obtained from normal cartilage and maintained in culture in alginate beads for 1 week to reach equilibrium of accumulated cell-associated matrix (CAM) compounds. Levels of CAM components aggrecan and type II collagen (CII) and levels of intracellular IGF-1, IL-1alpha, and IL-1beta and their respective plasma membrane-bound receptors IGFRI, IL-1 receptor I (IL-1RI), and the decoy receptor IL-1RII were assayed using flow cytometry to investigate the relationship between the autocrine/paracrine pathways and the homeostasis of ECM molecules in the CAM. The effects of IGF-1 on the expression of IGF-1, IL-1alpha, and IL-1beta and their respective receptor systems, the aggrecan core protein, and CII were determined by flow cytometry. RESULTS: Cause-effect relationship experiments showed that IGF-1 up-regulates the levels of IGF-1, IGFRI, aggrecan, and CII in the CAM. No effects on the expression of IL-1alpha and IL-1beta and their signaling receptor IL-1RI were observed. However, IGF-1 was able to reverse IL-1beta-mediated degradation of aggrecan and the repression of the aggrecan synthesis rate. Interestingly, levels of aggrecan and CII in the CAM strongly correlated not only with IGF-1, but also with IL-1RII, which acts as a decoy receptor for IL-1alpha and IL-1beta. This suggests that IGF-1 and IL-1RII may cooperate in regulating ECM homeostasis. Additional experiments demonstrated that IGF-1 up-regulated IL-1RII, thereby overriding the catabolic effects of IL-1. CONCLUSION: These findings reveal a new paradigm by which IGF-1 influences chondrocyte metabolism, by reversing the IL-1-mediated catabolic pathway through up-regulation of its decoy receptor.

Aggrecans↗