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At least 1,369 records · Page 76Linked to original sources
PubMed2005

[Use of fragrances. What about the side effects?].

Fragrances are increasingly used in private and public domains. Over recent years the olfactory sense has been paid more and more scientific and economic attention. While on the one hand bad smells are counteracted by fragrances, marketing experts are now trying to introduce this sense into multimedia-based experiences. Technical means are used to address positively and directly the sense of smell. The aim is to make the smell a unique feature for a certain brand or location. When it comes to "style of living" or "special shopping experience" nowadays the olfactory design plays an important role. Although fragrances are applied very frequently, there is still a lack of knowledge about the potential consequences for health and the environment. Certain substances (musk compounds) have been proven persistent and accumulative, and others belong to the most common causes of contact eczema. Some people also report special sensitivities towards certain smells for unknown reasons. Unlike audiovisual attractions it is very difficult for humans to avoid olfactory stimuli. The question arises whether fragrance materials constitute a group of substances that should receive more attention concerning their risk for health and the environment.

Allergens↗
PubMed1999

Two-photon Na+ imaging in spines and fine dendrites of central neurons.

Dendritic spines are assumed to be the smallest units of neuronal integration. Because of their miniature size, however, many of their functional properties are still unclear. New insights in spine physiology have been provided by two-photon laser-scanning microscopy which allows fluorescence imaging with high spatial resolution and minimal photodamage. For example, two-photon imaging has been employed successfully for the measurement of activity-induced calcium transients in individual spines. Here, we describe the first application of two-photon imaging to measure Na+ transients in spines and dendrites of CA1 pyramidal neurons in hippocampal slices. Whole-cell patch-clamped neurons were loaded with the Na(+)-indicator dye SBFI (sodium-binding benzofuran-isophthalate). In situ calibration of SBFI fluorescence with ionophores enabled the determination of the actual magnitude of the [Na+]i changes. We found that back-propagating action potentials (APs) evoked Na+ transients throughout the proximal part of the dendritic tree and adjacent spines. The action-potential-induced [Na+]i transients reached values of 4 mM for a train of 20 APs and monotonically decayed with a time constant of several seconds. These results represent the first demonstration of activity-induced Na+ accumulation in spines. Our results demonstrate that two-photon Na+ imaging represents a powerful tool for extending our knowledge on Na+ signaling in fine cellular subcompartments.

Action Potentials↗
PubMed1980

Pathogenesis of renal failure due to aminoglycosides and contrast media used in roentgenography.

The etiology of acute renal failure has changed in recent years due to the recognition of drug nephrotoxicity as a more common cause. In this communication we emphasize recent information concerning the pathophysiology of nephrotoxic acute renal failure produced by aminoglycoside antibiotics and the contrast media used in roentgenography. The aminoglycosides are excreted primarily by glomerular filtration; however, net tubular reabsorption and renal parenchymal accumulation do occur. The exact mechanism of uptake is not clear, but the luminal membrane seems primarily involved. The pathogenesis of nephrotoxicity, although probably linked to cortical accumulation, is complex since experimental animals recover from gentamicin-induced renal failure despite continued administration of the drug. Knowledge of the precise cellular mechanisms of injury awaits further studies. Histologic damage is usually limited to proximal tubular necrosis and, clinically, the renal failure is nonoliguric. Although reports of the contrast media used in roentgenography producing acute renal failure have increased, the pathogenesis is unclear. Evidence supporting various theories is reviewed.

Acute Kidney Injury↗
PubMed1975

The role of gamma-aminobutyric acid in the mechanism of seizures.

The knowledge that GABA is an inhibitory neurotransmitter substance in brain has spurred a prodigious research effort to implicate GABA in the etiology of seizures. Such an involvement for GABA can occur theoretically at either of two levels, at the level of its metabolism or at the level of its functioning. Convulsant agents such as picrotoxin and bicuculline appear to act by impairing the functioning of GABA at the postsynaptic receptor site, but virtually nothing is known about the attendant molecular events although a major expansion of knowledge in this area may be expected within the next decade. In contrast, a vast amount of data has accumulated with respect to changes in GABA metabolism induced by convulsant agents such as the hydrazines, hydrazides, and hyperbaric oxygen. The problem in this case lies in the interpretation of the data. Are the changes in GABA metabolism the cause of the seizures? There is clearly no simple relationship between seizure activity and any single parameter of GABA metabolism, be it the GABA content of the brain, or the rate of uptake of GABA by cellular components, or the activity of the GABA-synthesizing and degrading enzyme systems, GAD and GABA-T respectively. This finding may, however, be illusory since the parameters of GABA metabolism were in most cases measured using preparations from intact brain tissue. Observed changes in the parameters may not accurately reflect events at a critical subcellular location such as the synaptic cleft. Thus there may well be a simple relationship between the concentration of GABA in the synaptic cleft and seizure activity. Unfortunately the limitations of current technology preclude the testing of this possibility. The author has, however, developed an equation on an empirical basis which provides an excellent relationship between the excitable state of the brain and a function of GABA metabolism which incorporates both changes in GABA level and changes in GAD activity. This equation has been used successfully to explain and rationalize previously anomalous results with respect to changes in GABA metabolism associated with the action of both convulsant and anticonvulsant agents. The concept embodied in the equation is that the excitable state of brain is determined primarily by the rate of synthesis of GABA but that reflects changes in the concentration of GABA in the synaptic cleft has been suggested.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2001

The central opioid system in liver disease and its complications.

The best known example of an interaction between the liver and the brain is hepatic encephalopathy. In the 90s a central nervous system origin of the pruritus of cholestatic liver disease and more recently of fatigue of liver disease has been suggested. Hence, three important manifestations of liver disease may be of central origin. Evidence is accumulating that the central opioid system is involved in the development of these manifestations. This short review summarizes current knowledge on the role of the opioid system in development of these liver disease manifestations.

Fatigue↗
PubMed2006

The nitrate/proton antiporter AtCLCa mediates nitrate accumulation in plant vacuoles.

Nitrate, the major nitrogen source for most plants, is widely used as a fertilizer and as a result has become a predominant freshwater pollutant. Plants need nitrate for growth and store most of it in the central vacuole. Some members of the chloride channel (CLC) protein family, such as the torpedo-fish ClC-0 and mammalian ClC-1, are anion channels, whereas the bacterial ClC-ec1 and mammalian ClC-4 and ClC-5 have recently been characterized as Cl-/H+ exchangers with unknown cellular functions. Plant members of the CLC family are proposed to be anion channels involved in nitrate homeostasis; however, direct evidence for anion transport mediated by a plant CLC is still lacking. Here we show that Arabidopsis thaliana CLCa (AtCLCa) is localized to an intracellular membrane, the tonoplast of the plant vacuole, which is amenable to electrophysiological studies, and we provide direct evidence for its anion transport ability. We demonstrate that AtCLCa is able to accumulate specifically nitrate in the vacuole and behaves as a NO3-/H+ exchanger. For the first time, to our knowledge, the transport activity of a plant CLC is revealed, the antiporter mechanism of a CLC protein is investigated in a native membrane system, and this property is directly connected with its physiological role.

Arabidopsis↗
PubMedDate not supplied

Epidemiologic aspects on low-back pain in industry.

The role of epidemiology with respect to back pain in industry is to clarify the natural history and clinical course of the pain and to identify workplace factors and individual factors of importance. On the basis of knowledge obtained through epidemiologic research, preventive measures can be instituted and risk factors eliminated. This paper reviews epidemiological data accumulated over the past 30 years. The impact of back conditions on industry is emphasized.

Adult↗
PubMed1980

Developing education for children with asthma through study of self-management behavior.

Bronchial asthma is the major cause of disability in childhood. Among its effects are impaired levels of physical activity and self-esteem, reduced school attendance and performance, and increased utilization of emergency health services. This paper describes the development of a health education program designed to test the hypothesis that better family self-management of asthma can reduce the negative impact of the disease. Three hundred low income Black and Hispanic families were enrolled in the study. Children and primary caretakers were interviewed separately to obtain baseline data on current levels of self-management and to assess needs for educational intervention. Data have been accumulated on a variety of topics concerning asthma self-management, including health practices and beliefs, coping skills, asthma knowledge, and locus of control. An Asthma Self-Management Index was developed to measure positive management behaviors by the family. The needs assessment indicated that six core themes were priorities for these families in terms of relevant skills and behaviors. These topics were incorporated as lesson plans in the intervention.

Asthma↗
PubMed2006

Quantitative cell-cycle protein expression in oral cancer assessed by computer-assisted system.

The knowledge of cell-cycle control has shown that the capacity of malignant growth is acquired by the stepwise accumulation of defects in specific genes regulating cell growth. Histologic diagnosis might be improved by a quantitative evaluation of more specific diagnosis biomarkers, which could help to precisely identify pre-malignant and malignant oral lesions. The aim of the present study is to evaluate whether computer-based quantitative assessment of p53, PCNA and Ki-67 immunohistochemical expression, could be used clinically to foresee the risk of oral malignant transformation. This retrospective study was carried out in ninety-five oral biopsies, 27 were classified as fibrous inflammatory hyperplasia, 40 as leukoplakia and 28 as oral squamous cell carcinoma. Sixteen out of the 40 leukoplakia were diagnosed as non-dysplastic leukoplakia, the other 24 being dysplastic leukoplakia, of which 50.0% were classified as moderate to severe dysplasia. Comparison of the four groups of oral tissues showed significant rises in p53 and Ki-67 positivity index, which increased steadily in the order benign, pre-malignant, and malignant. In contrast, it was not possible to relate higher PCNA levels with pre-malignant and malignant oral lesions. We therefore conclude that PCNA immunohistochemistry expression is probably an inappropriate marker to identify oral carcinogenesis, whereas joint quantitative evaluation of p53 and Ki-67, appears to be useful as a tumor marker, providing a pre-diagnostic estimate of the potential for cell-cycle deregulation of the oral proliferate status.

Biomarkers, Tumor↗
PubMedDate not supplied

Interpretation of drug levels in acute and chronic disease states.

Serum drug concentration monitoring can be an invaluable aid to patient management, particularly in certain pathological conditions when individualisation of dosage is particularly critical. To be clinically useful, however, drug levels must be interpreted in the context of all factors that could influence the correlation between the concentration of the drug in plasma and the intensity of action. Several such factors may be operating in acute and chronic disease states. For example, a number of pathological conditions are associated with marked changes in the fraction of free, pharmacologically active drug in plasma and this will result in disruption of the normal relationship between total serum drug level and effect, as seen for phenytoin in uraemia. An altered response to a given serum drug level in disease states may also be caused by changes in tissue distribution, by abnormal accumulation of pharmacologically active metabolites in plasma or by changes in end-organ responsiveness. The latter are best illustrated by the altered sensitivity to digoxin in patients with various conditions, including hypokalaemia and thyroid disease. In addition to the factors listed above, consideration should also be given to potential interactions with concomitantly used drugs and to the possibility of analytical errors, especially in view of the evidence that the performance of otherwise reliable drug assays may be grossly impaired in certain diseases (e.g. uraemia), due to abnormal plasma composition and/or accumulation of interfering metabolites. In view of these complexities, a correct interpretation of serum drug levels requires a good knowledge of clinical pharmacology and a close collaboration between physician and laboratory. In any case, serum drug concentrations, like other laboratory tests, are not a substitute for careful patient observation, and any decision about drug treatment should be primarily based upon evaluation of the clinical state and, whenever possible, direct measurement of drug effects.

Acute Disease↗
PubMed2003

Autosomal dominant familial neurohypophyseal diabetes insipidus.

Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is a rare disorder caused by progressive postnatal arginine vasopressin (AVP) deficiency resulting from mutations in the AVP gene encoding the AVP pre-prohormone. It has been suggested that these mutations exert their effect on the cellular handling of the AVP prohormone by leading to the synthesis of mutant hormone precursor that fails to be processed and/or folded properly in the endoplasmic reticulum (ER). As a consequence, it is retained by the ER protein quality control machinery resulting in protein accumulation and initiation of cellular processes leading to degeneration of the AVP producing neuron. This review summarizes the current knowledge on adFNDI and discusses different hypotheses concerning its pathogenesis.

Arginine Vasopressin↗
PubMedDate not supplied

[Physiopathology of dementia of the Alzheimer type: role of the amyloid beta-protein].

Biological research on Alzheimer's disease is expanding quickly, and the mechanisms of the disease are better understood today. Progress has been specially impressive in the knowledge of the brain lesions (senile plaques, neurofibrillary degeneration). It is likely that the beta-amyloid protein, which accumulates in the senile plaques plays a major role in the development of the brain lesions and, subsequently of the clinical symptoms. The metabolism of the precursor of this protein might be abnormal, leading to the beta-amyloid protein deposits. Some discrete genetic abnormalities (such as punctate mutations on the beta amyloid precursor gene) have been described recently in familial cases of the disease. It seems unlikely that such punctate mutations would be responsible for the majority of the cases. Therefore it is possible that Alzheimer's disease has multiple causes, the genetic factors being only one of them.

Aged↗
PubMed1989

[Involvement of lipid peroxidation in regression of heart hypertrophy].

The regression of hypertrophied heart presupposes disassembling of all cardiomyocyte components including membrane structures. The involvement of free radical oxidation of membrane phospholipids was studied in the cardiac regression. Altitude hypertrophy was developed in barocamera (7000 m, 6 hours daily). 3 weeks of periodical hypoxia leads to 1.5-fold increase of heart weight (right ventricle weight was 2-fold increased). In 7-10 days after adaptation the heart weight reduced to normal. Both, the development and regression of myocardial hypertrophy was accompanied by changes in Mb and Hb organ concentration proportional to weight changes. In lipid extraction of maximal hypertrophied heart, the 30% decrease of lipid peroxidation product (diene conjugates) regularly occurred. The rate of regression had negative correlation with peroxidation products accumulation. Intraperitoneal injection of free radical scavenger BHT attenuate the regression rate. The results suggest that unlike the common knowledge about the membrane injury effect, lipid peroxidation can play positive role in disassembling of superfluous cell membrane structures.

Animals↗
PubMed1986

Analysis of renal structural and functional features in two rat strains with a different susceptibility to glomerular sclerosis.

Individual differences in susceptibility to the development of focal and segmental glomerular hyalinosis and sclerosis (FSGHS) after loss of renal mass were studied in two rat strains. Male Wistar rats, and most other rat strains, were found to develop FSGHS associated with proteinuria with ageing, a process which could be accelerated by unilateral nephrectomy (UN). In male PVG/c rats, however, a complete resistance to the development of FSGHS was found even at 1 year after UN. The Wistar rat was found to have a lower number of nephrons per kidney and to differ from the PVG/c rat in its response to UN: Wistar rats showed an increase of whole kidney glomerular filtration rate and renal plasma flow in the remaining kidney with expansion of glomerular volume and with increased mesangial deposition of circulating macromolecules. In the PVG/c rat, UN led to a comparable proportional increase in glomerular filtration rate and renal plasma flow in the remaining kidney. However, in contrast to the Wistar rat neither glomerular hypertrophy nor enhanced mesangial macromolecular accumulation were observed after UN. Although the precise mechanisms underlying these effects are not identified, the current data support the "mesangial overloading" concept of FSGHS in which a local enhanced mesangial accumulation of circulating macromolecular material is thought to initiate the development of the sclerotic glomerular lesions. Moreover, to our knowledge this is the first description of a rat strain showing complete resistance to the development of FSGHS after UN. This PVG/c strain therefore seems to be a useful laboratory animal in comparison to other rat strains to further study the renal adaptation process after kidney ablation.

Animals↗
PubMed1993

Medically relevant laboratory-performance goals: a listing of the complexities and a call for action.

This 1992 Clinical Chemistry Forum asks if accuracy and precision goals for the laboratory can be specified by reference to medical requirements, which are a function of the total laboratory testing process as well as the needs of patients, clinicians, and societal institutions. Furthermore, medical decisions and decisions about medical requirements must be made in situations of uncertainty and thus are subject to predictable cognitive errors. The interaction of all these factors must be considered by patients, laboratorians, and clinicians to identify practical and effective performance goals. Pathologists and clinical chemists are uniquely trained to identify thoughtful clinicians who are knowledgeable in quantitative judgment to participate in this goal-setting endeavor. It is time for these parties to accumulate the available data and engage in the synthesis of effective performance goals.

Bias↗
PubMed1993

Cancer genes.

Cancer is a genetic disease; tumor cells differ from their normal progenitors by genetic alterations that affect growth-regulatory genes. There exist 2 classes of such cancer genes: the oncogenes, which function as positive growth regulators, and the tumor suppressor genes, which function as negative growth regulators. Oncogenes are widely conserved among diverse forms of life and are active in transmitting growth signals from the cell periphery to the cell nucleus. These signaling functions can be disturbed by many types of genetic change; the result of an altered growth signal is often cancer. Tumor suppressor genes have an attenuating effect on cell growth that is lost as a result of inactivating mutations or deletion of the gene; in DNA virus-transformed cells, it is abrogated by neutralization of the tumor suppressor protein through a viral gene product. Tumor suppressor genes were first recognized in inherited cancers; defects in a tumor suppressor transmitted through the germ line can lead to increased tumor incidence in the offspring. Tumor suppressors also play important roles in nonheritable cancer, however; many tumors in humans show defects in tumor suppressor genes. Most cancers harbor multiple genetic changes in oncogenes as well as tumor suppressor genes. Oncogenes induce aberrant growth through a gain in function; tumor suppressor genes contribute to oncogenesis through a loss of function. Both types of mutation work together to produce cancer; the changes are not constant but increase in number as the tumor develops from benign to more and more malignant. Cancer results from the accumulation of genetic changes. Oncogenes and tumor suppressor genes provide important insights into the regulation of cell growth. This knowledge can now be used to develop gene-specific therapies for cancer.

Animals↗
PubMed1997

Activation of the NF-kappaB pathway by inflammatory stimuli in human neutrophils.

Activated neutrophils have the ability to upregulate the expression of many genes, in particular those encoding cytokines and chemokines, and to subsequently release the corresponding proteins. Although little is known to date concerning the regulation of gene transcription in neutrophils, it is noteworthy that many of these genes depend on the activation of transcription factors, such as NF-kappaB, for inducible expression. We therefore investigated whether NF-kappaB/Rel proteins are expressed in human neutrophils, as well as their fate on cell activation. We now report that dimers consisting of p50 NFkappaB1, p65 RelA, and/or c-Rel are present in neutrophils and that the greater part of these protein complexes is physically associated with cytoplasmic IkappaB-alpha in resting cells. Following neutrophil stimulation with proinflammatory agonists (such as lipopolysaccharide [LPS], tumor necrosis factor-alpha [TNF-alpha], and fMet-Leu-Phe) that induce the production of cytokines and chemokines in these cells, NF-kappaB/Rel proteins translocated to nuclear fractions, resulting in a transient induction of NF-kappaB DNA binding activity, as determined in gel mobility shift assays. The onset of both processes was found to be closely paralleled by, and dependent on, IkappaB-alpha degradation. Proinflammatory neutrophil stimuli also promoted the accumulation of IkappaB-alpha mRNA transcripts, resulting in the reexpression of the IkappaB-alpha protein. To our knowledge, this constitutes the first indication that NF-kappaB activation may underlie the action of proinflammatory stimuli towards human neutrophil gene expression and, as such, adds a new facet to our understanding of neutrophil biology.

Base Sequence↗
PubMed2003

HIV disease in primary care.

During the past decade, a large number of new drugs for treating HIV and its complications have been developed. The increasingly sophisticated use of these drugs in combination has led to a marked reduction in HIV-related morbidity and mortality in countries where they are available. HIV/AIDS patients receiving treatment are now expected to live into old age. The beneficial effect of HIV treatment has resulted in an expanding population of persons living with HIV/AIDS who will need the care of an HIV specialist because of the complexity of the treatment regimens and the rapidly changing HIV/AIDS knowledge base. However, this growing and aging population will also benefit from the care of a primary care physician. The primary care generalist is in the best position to recognize and diagnose HIV infection, evaluate HIV risk in his or her patient population, and help prevent HIV infection in persons at risk. In patients known to be infected, the primary care generalist will be best able to manage hyperlipidemia, diabetes, cardiovascular disease, and other disorders of an aging population with an increased risk of these and other conditions. Patients with HIV infection frequently accumulate a large number of specialist physicians, and the unique ability of the primary care physician to monitor their care and act as a knowledgeable patient advocate is a great benefit to the patient.

AIDS-Related Opportunistic Infections↗