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At least 1,387 records · Page 77Linked to original sources
PubMed1993

[Non-cholinergic effects of organophosphates].

The author summarizes contemporary knowledge on the action of organophosphates with emphasis on non-cholinergic mechanisms. Intoxication with these substances is characterized by four basic processes: absorption, transport, metabolism and the toxic effect proper. The latter involves cholinesterase inhibition at the cholinergic synapses with subsequent accumulation of acetylcholine. However, non-cholinergic processes are also involved such as the effect on levels of cyclic nucleotides, the peptidergic system, receptors, liver metabolism and the stressogenic action. From the review ensues that knowledge of non-cholinergic, mechanisms of action could reveal new approaches to treatment of intoxications with these substances.

Animals↗
PubMed1990

Altered cellular distribution of iron in the central nervous system of myelin deficient rats.

Under normal conditions, iron is found predominantly in oligodendrocytes, the myelin producing cell, in the rat brain. A genetic mutant strain of rats known as myelin deficient rats is examined in the present study because their number of oligodendrocytes is decreased and those oligodendrocytes present are structurally abnormal. The levels of iron in the liver (major site of iron storage) and in the pons-cerebellum did not differ statistically between the myelin deficient rats and the littermate control rats, whereas only half of the iron normally found in the cerebrum-midbrain was present in the myelin deficient rat. Histologically, iron was found predominantly in oligodendrocytes in the littermate control rats, as expected. In the myelin deficient rat, iron staining was confirmed to astrocytes and microglia. The results of this study strongly suggest that iron uptake into the brain continues in the absence of normal oligodendrocytes and myelin. Furthermore, these data suggest that iron metabolism can be substantially altered, as indicated by the accumulation of iron in astrocytes and microglia, when normal or near normal levels of iron are quantitatively demonstrated. The response of astrocytes and microglia to sequester the iron (presumably through phagocytosis) in the absence of invasive damage represents, to our knowledge, a new functional observation for these cells. Based on these observations it is clear that iron histochemistry in combination with quantitative analysis is necessary to interpret data regarding iron physiology, at least in neurobiology, and iron accumulation by astrocytes and microglia may provide clues of altered iron metabolism despite normal iron levels.

Animals↗
PubMed1999

Restrictions to carbon dioxide conductance and photosynthesis in spinach leaves recovering from salt stress

Salt accumulation in spinach (Spinacia oleracea L.) leaves first inhibits photosynthesis by decreasing stomatal and mesophyll conductances to CO2 diffusion and then impairs ribulose-1, 5-bisphosphate carboxylase/oxygenase (S. Delfine, A. Alvino, M. Zacchini, F. Loreto [1998] Aust J Plant Physiol 25: 395-402). We measured gas exchange and fluorescence in spinach recovering from salt accumulation. When a 21-d salt accumulation was reversed by 2 weeks of salt-free irrigation (rewatering), stomatal and mesophyll conductances and photosynthesis partially recovered. For the first time, to our knowledge, it is shown that a reduction of mesophyll conductance can be reversed and that this may influence photosynthesis. Photosynthesis and conductances did not recover when salt drainage was restricted and Na content in the leaves was greater than 3% of the dry matter. Incomplete recovery of photosynthesis in rewatered and control leaves may be attributed to an age-related reduction of conductances. Biochemical properties were not affected by the 21-d salt accumulation. However, ribulose-1, 5-bisphosphate carboxylase/oxygenase activity and content were reduced by a 36- to 50-d salt accumulation. Photochemical efficiency was reduced only in 50-d salt-stressed leaves because of a decrease in the fraction of open photosystem II centers. A reduction in chlorophyll content and an increase in the chlorophyll a/b ratio were observed in 43- and 50-d salt-stressed leaves. Low chlorophyll affects light absorptance but is unlikely to change light partitioning between photosystems.

Journal Article↗
PubMed1999

Cytokine generation in whole blood, leukocyte-depleted and temporarily warmed red blood cell concentrates.

BACKGROUND AND OBJECTIVES: It has been suggested that inflammatory cytokines such as Interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha) and IL-8 might be responsible for a large number of non-antibody-mediated adverse reactions to the transfusion of blood components, especially of platelet concentrates (PCs). The aim of this study was to compare the levels of proinflammatory cytokines in different blood components containing red cells such as buffy-coat-free packed red cells (RBCs), filtered RBCs and whole blood (WB) during storage under several conditions. MATERIALS AND METHODS: WB (CPD-A1, n = 16) was stored for 35 days at 2-6 degrees C; samples were taken on days 0, 21 and 35. Buffy-coat-poor RBCs in additive solution PAGGS-M (n = 16) were divided into halves, one half was leukocyte (WBC)-depleted by filtration on day 0, both halves were stored for 49 days at 2-6 degrees C (samples: days 0, 21, 49). Furthermore, buffy-coat-poor, unfiltered SAG-M RBCs (n = 16) were halved immediately after production and stored at 2-6 degrees C until day 42 (samples: days 0, 21, 42). One half remained at room temperature for 24 h on day 3. Cytokine levels were determined with commercial enzyme-linked immunosorbent assays. RESULTS: Levels of IL-1beta and TNF-alpha rose during storage of WB and RBCs. IL-6 could be detected markedly above the detection threshold in WB only. At the end of storage, we detected IL-8 in 1 of 16 units of WB tested, in 10 of 16 standard PAGGS-M RBCs and in 15 of 16 temporarily warmed SAG-M RBCs. Prestorage filtration of RBCs prevented the accumulation of IL-1beta and TNF-alpha. Temporarily warming of RBCs for 24 h did not cause any substantial increase in cytokine levels other than IL-8. RBCs stored in different additive solutions (PAGGS-M versus SAG-M) showed similar cytokine concentrations during storage. The cytokine content of WB was very similar to that of buffy-coat-poor RBCs. CONCLUSION: Cytokine levels measured in WB and buffy-coat-poor RBCs result in levels which are unlikely to cause febrile reactions even in the case of massive transfusion. We conclude that, according to present knowledge, there is no reason for prestorage filtration of buffy-coat-poor RBCs or WB to avoid febrile transfusion reactions due to cytokine accumulation during storage.

Blood Preservation↗
PubMed2006

[Popular nosology of infantile diseases in West Côte-d'Ivoire and consequences for malaria care management].

In a rural area of intense and permanent malaria transmission in Southwest Côte-d'lvoire, traditional midwifes of the Yacouba ethnic group, with also an important function for the children health and care, were interviewed in 2002 about their knowledge of the infantile pathologies. Their nosology is greatly based on symptoms and etiologic explanations of the disorder of secretions. The accumulation of a viscous liquid in different parts of the body, especially in the chest, the throat or the head, explains numerous febrile or afebrile diseases, including malnutrition. Some pathologies, particularly convulsions, are described by analogy with animals behaviour Relations between these entities and the biomedical ones are difficult to establish. The traditional care and treatments result from these concepts. A vomiting child or a child suffering from diarrhoea is subject to devices to evacuate his excess of liquid. Yellow brews are used against jaundice. Furthermore, an important mistrust remains towards medical treatments particularly for all parenteral therapies. Health facilities are only used as a the last resort. Their bad reputation is confirmed by the high rate of mortality of patients coming often too late. To improve malaria care management, health-care workers have to take into consideration these concepts and also prove their abilities to ensure good medical practices.

Child↗
PubMed1996

Human immunodeficiency virus replication in the presence of antiretroviral drugs: analogies to antineoplastic drug resistance.

There are many analogies between antineoplastic therapy and antiviral therapy. For each there may be sanctuary sites in which the drug is ineffective because of decreased accumulation of the active form of the drug or increased competition by naturally occurring inhibitors. These sanctuaries may be restricted to anatomic or biochemical subsets of the population. A knowledge of these sanctuaries is essential to an understanding of the failure of therapy and for the design of more effective treatments. Eradication of these sanctuary sites may be important because they may be responsible for the viral replication or tumor cell division that continues to generate the diversity that drives clonal evolution. Ultimately, diversity as a consequence of the accumulation of mutations results in the selection of resistant viral or tumor cell variants and the failure of drug therapy. Maximizing therapy in an attempt to diminish the rate of generation of this diversity may result in better clinical outcomes, including a delay in the generation of variants with genetic drug resistance.

Antineoplastic Agents↗
PubMed2004

[Cardiac manifestation of Fabry's disease: current knowledge].

Fabry's disease is a rare lysosomal storage disease caused by the X-linked defect of the enzyme alpha-galactosidase A leading to the intracellular accumulation of glycosphingolipids in various organs and tissues. Cardiac involvement is frequent and, in individuals with some residual enzyme activity, may be the sole manifestation of the disease. Hemizygous men are generally more seriously affected than heterozygous women. The dominant cardiac manifestations include myocardial hypertrophy of the left ventricle, which, in some patients, mimics hypertrophic cardiomypathy. Left ventricular systolic function is usually preserved, on the other hand mild to moderate diastolic dysfunction is regularly detected. Valvular abnormalities are frequently noted. However, hemodynamically significant lesions are rare. Conduction system involvement leads initially to the shortening of atrioventricular conduction, in later stages, with a progression of the disease, antrioventricular blocks and various forms of supraventricular and ventricular arrhythmias appear. Myocardial ischemia in Fabry disease has in most cases a functional origin due to endothelial dysfunction of coronary arteries and also due to the increase oxygen demand of hypertrophied myocardium. The results of so far performed studies with enzyme replacement therapy are promising in preventing further deterioration and even improving function of affected organs.

Fabry Disease↗
PubMed2004

High hydrostatic pressure induces ERK and PI3 kinase phosphorylation in human HCS-2/8 chondrosarcoma cells.

High continuous hydrostatic pressure has been shown to affect many cellular functions within the pressurised cells, for instance, accumulation of heat shock protein 70 occurs during pressurisation. Various signal transduction pathways are likely to mediate these changes, however, at the present time our knowledge of the pathways involved is rather limited. The aim of this study was to investigate whether some of the well known transduction pathways are activated by the exposure of human chondrosarcoma cells to 15-30 MPa hydrostatic pressure. The results showed an increased presence of the active, phosphorylated forms of extracellular signal-related kinase (ERK) and phosphoinositide 3-kinase (PI3K) in cells exposed to 15 and 30 MPa continuous hydrostatic pressure, while 0.5 Hz cyclic loading had weaker effects. Inhibition of ERK-pathway with UO126 did not prevent the accumulation of heat shock protein 70. No activation of c-Jun N-terminal protein kinase (JNK) or p38 could be noticed in pressurised cells. In conclusion, we could identify at least two different signal transduction pathways that are activated under high continuous hydrostatic pressure. Accumulation of heat shock protein 70 was independent of ERK-activation.

Cell Line, Tumor↗
PubMed1993

Bioactivation of nephrotoxins and renal carcinogens by glutathione S-conjugate formation.

Evidence has been accumulating that several classes of compounds are converted by glutathione conjugate formation to toxic metabolites. The aim of this review is to summarize the current knowledge on the biosynthesis and toxicity of glutathione S-conjugates derived from halogenated alkenes, and hydroquinones and quinones. Different types of toxic glutathione conjugates have been identified in detail; (i) conjugates which are converted to toxic metabolites in an enzyme-catalyzed multistep mechanism and (ii) conjugates which serve as a transport form for toxic quinones will be discussed. The kidney is the main, with some compounds the exclusive, target organ for compounds metabolized by these pathways. Selective toxicity to the kidney is easily explained due to the capability of the kidney to accumulate intermediates formed by processing of S-conjugates and to bioactivate these intermediates to toxic metabolites. The influences of other factors participating in the renal susceptibility and influencing human risk assessment for these compounds are discussed.

Animals↗
PubMed2006

Refolding of a small all beta-sheet protein proceeds with accumulation of kinetic intermediates.

The refolding kinetics of Cobrotoxin (CBTX), a small all beta-sheet protein is investigated using a variety of biophysical techniques including quenched-flow hydrogen-deuterium (H/D) exchange in conjunction with two-dimensional NMR spectroscopy. Urea-induced equilibrium unfolding of CBTX follows a two-state mechanism with no distinct intermediates. The protein is observed to fold very rapidly within 250 ms. Both the refolding and the unfolding limbs of the chevron plot of CBTX show a prominent curvature suggesting the accumulation of kinetic intermediates. Quenched-flow H/D exchange data suggest the presence of a broad continuum of kinetic intermediates between the unfolded and native states of the protein. Comparison of the native state hydrogen exchange data and the results of the quenched-flow H/D exchange experiments, reveals that the residues constituting the folding core of CBTX are not a subset of the slow exchange core. To our knowledge, this is the first report wherein the refolding of a small all beta-sheet protein is shown to be a multi-step process involving the accumulation of kinetic intermediates.

Cobra Neurotoxin Proteins↗
PubMed2003

Cyclin E overexpression and amplification in human tumours.

Cyclin E amplification and overexpression have recently been described in several tumour types. However, many tumour entities have never been examined for cyclin E alterations. Numerous and time-consuming experiments were previously required to determine the significance of potential oncogenes across different tumour types. To overcome this problem, tissue microarrays (TMAs) consisting of 3670 primary tumours from 128 different tumour types, 709 metastases, and 354 normal tissues were generated. Cyclin E alterations were then analysed by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Cyclin E gene amplification was observed in 15 different tumour types and subtypes, ie rhabdomyosarcoma, urinary bladder cancer (three subtypes), ovarian cancer (two subtypes), malignant fibrous histiocytoma, adenocarcinoma of the small intestine, medullary breast cancer, gall bladder adenocarcinoma, phaeochromocytoma, gastric adenocarcinoma, squamous cell carcinoma of the uterine cervix, colonic adenocarcinoma, and endometrial carcinoma. Cyclin E protein accumulation was found in 48 different tumour types. The use of TMA technology has enabled us to expand considerably our knowledge of cyclin E alterations in human tumours. The occurrence of amplification and overexpression in many different tumour types suggests that cyclin E plays an important role in tumour biology.

Cyclin E↗
PubMed1998

Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin to several ecological receptor groups: a short review.

Toxicity among TCDD isomers can vary significantly. Isomers containing four to six chlorine atoms possess the greatest potential for biological activity, as well as the highest acute toxicity. Information available in the literature focuses largely on fish and terrestrial mammal studies. Toxicity data for aquatic invertebrates and plants is wanting, and essentially no studies pertaining to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) accumulation in these organisms could be found. No data were procurable regarding TCDD toxicity in marine mammals or reptiles. Current knowledge is not sufficient to accurately characterize TCDD toxicity in ecological receptors, with quantification of uncertainty being particularly difficult given the limited base of knowledge.

Animals↗
PubMed1989

Developmental cardiac metabolism in health and disease.

Cardiac metabolism changes in response to oxygen and substrate availability during development. The fetus is relatively more dependent on anaerobic glycolysis, using glucose as its major substrate during hypoxia, lactate when well-oxygenated. The mature heart is almost exclusively aerobic, with nonesterified fatty acids as the predominant substrate. During hypoxia and ischemia, shifting the heart to carbohydrate metabolism has oxygen-sparing effects. Blocking lipolysis or carnitine palmityl transferase activity prevents accumulation of potentially toxic long-chain esters during hypoxia/ischemia, thereby reducing the risk of electrophysiologic disturbance and membrane disruption. Knowledge of developmental cardiac metabolism may aid in the development of therapeutic strategies to preserve the myocardium during hypoxia and ischemia.

Carbohydrates↗
PubMed1998

Oncocytic tumours.

Oncocytic tumours represent a distinctive set of lesions with distinctive granular cytoplasmic eosinophilia of the neoplastic cells. These cells are called oncocytes because of the "swollen" appearance they have as the result of a striking accumulation of mitochondria. Although generally uncommon, oncocytic tumours are by no means rare and have been reported, with different frequencies, in virtually every organ. A variety of biochemical and molecular changes have been identified, and the aberrant biogenesis of mitochondria in oncocytic cells bears intriguing similarities to that of a group of degenerative disorders known as mitochondrial encephalomyopathies. Although the relationship between the accumulation of mitochondria and the occurrence of tumours is unknown, investigation into the cellular alterations of oncocytes may further our knowledge of a variety of important biological processes such as proliferation, energy production and ageing.

Adenocarcinoma↗
PubMed1993

Two-liquid-phase bioreactors.

The application of two liquid phases that are poorly miscible is a fascinating research topic for biocatalytical conversions because of the promising results. Motives for application include an increase of productivity and achievement of continuous processing, but new limitations arise, e.g., interfacial effects such as biocatalyst accumulation and loss of activity, medium component accumulation, and slow coalescence. Centrifuges, membranes, and immobilization are tools that can overcome part of the problems, but more fundamental knowledge about interfaces and coalescence is still necessary for successful application. For scaleup and further development of processes based on the obtained results, a choice must be made for the configuration of the experimental setup of a bioreactor. Aspects like aeration, shear stress, batch or continuous processing, and immobilization can play an important role. This review article describes these aspects and the proposals that have been made in recent years concerning two-liquid-phase bioreactors. It shows some adaptations to existing bioreactors, such as loop reactors and stirred-tank reactors.

Biodegradation, Environmental↗
PubMed2004

The thalamic reticular nucleus: structure, function and concept.

On the basis of theoretical, anatomical, psychological and physiological considerations, Francis Crick (1984) proposed that, during selective attention, the thalamic reticular nucleus (TRN) controls the internal attentional searchlight that simultaneously highlights all the neural circuits called on by the object of attention. In other words, he submitted that during either perception, or the preparation and execution of any cognitive and/or motor task, the TRN sets all the corresponding thalamocortical (TC) circuits in motion. Over the last two decades, behavioural, electrophysiological, anatomical and neurochemical findings have been accumulating, supporting the complex nature of the TRN and raising questions about the validity of this speculative hypothesis. Indeed, our knowledge of the actual functioning of the TRN is still sprinkled with unresolved questions. Therefore, the time has come to join forces and discuss some recent cellular and network findings concerning this diencephalic GABAergic structure, which plays important roles during various states of consciousness. On the whole, the present critical survey emphasizes the TRN's complexity, and provides arguments combining anatomy, physiology and cognitive psychology.

Attention↗
PubMed2000

Antimicrobial pharmacodynamics.

The ultimate goal of antimicrobial therapy is to provide the best possible outcomes for patients. For this to occur, the clinician should be cognizant of many clinical, microbiologic, pharmacologic, and epidemiologic data as well as fundamental pharmacodynamic concepts. An understanding of pharmacodynamic principles is essential; it forms the scientific basis for the design of dosing strategies that maximize clinical efficacy and minimize toxicity. In the 1990s, data accumulated from in vitro models of infection, animal models of infection, healthy volunteer studies, and clinical trials that have expanded knowledge on how drugs best kill microorganisms. This knowledge has enabled clinicians to establish the best modes of antibiotic administration to maximize the killing of microorganisms and to optimize clinical outcomes.

Aminoglycosides↗
PubMed1998

Identification and developmental expression of a Bombyx mori alpha-tubulin gene.

A cDNA clone isolated from the wing discs at the metamorphosis of Bombyx mori during the period of morphogenesis has been characterized. The amino acid sequence predicted for the putative protein is highly homologous to the Drosophila alpha1-tubulin. This is the first alpha-tubulin gene isolated in Bombyx mori and other isotype sequences are present in the Bombyx genome. The transcript is detected in the wing discs at every postembryonic stage examined, and is also expressed in other tissues, but at different levels. Although the mRNA level is maximum when the 20-hydroxyecdysone titre is high, its accumulation is independent of the hormone level both in vivo and in vitro. Significance of the accumulation of the mRNA of an ubiquitous alpha-tubulin in developing wing discs is discussed by comparison with our knowledge of the alpha-tubulin family in Drosophila and in other organisms.

Amino Acid Sequence↗