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PubMed1993

[Anesthesia and porphyria].

The porphyrias are a group of disorders of haem metabolism. A knowledge of which anaesthetic can precipitate an acute attack of porphyria is important, since an accumulation of metabolites can result in life threatening symptoms, such as abdominal pain, vomiting, photophobia, neuropathy, bulbar paresis and respiratory failure. Treatment consists primarily of adequate calorie intake e.g. glucose, but is otherwise symptomatic. Anaesthetic drug recommendations are based both on animal experiments and patient experience, primarily case histories. An array of local anaesthetics, hypnotics, sedatives, neuroleptics, analgesics, muscle relaxants, inhalation anaesthetics and some antibiotics are reviewed. Patients with a history of porphyria should be in an optimal condition and maintain a high calorie intake perioperatively. The pre-operative fast should be a minimum and iv-glucose is advisable while fasting. There are anaesthetic agents that are safe for both regional and general anaesthesia.

Analgesics↗
PubMed2003

A histological analysis of lens capsules stained with trypan blue for capsulorrhexis in phacoemulsification cataract surgery.

PURPOSE: Staining of anterior lens capsules with dye to facilitate completion of continuous curvilinear capsulorrhexis is now being used more frequently in phacoemulsification of white and mature cataracts with poor red reflexes. This study examined the histological characteristics of anterior lens capsules stained with trypan blue. The layer(s) of the lens capsule that stained with dye and the extent of accumulation of dye in these layers of the lens capsule were determined. To the best of our knowledge this has not been described before. METHODS: A series of 10 stained lens capsules were analysed histologically. The dye used in this study consisted of a standard sterile, noninflammatory, nonpyrogenic, 2 ml solution containing 0.6 mg/ml of trypan blue. Following capsulorrhexis, samples were sent to the laboratory for histological analysis. Frozen sections (8 microm) were prepared and examined with the light microscope. All 10 capsules were cut by frozen section to preserve trypan blue staining (which would be leached by processing) and then subjected to immunohistochemistry for collagen IV. Immunohistochemical analysis using markers for type IV collagen were done on formalin-fixed specimens for morphological comparison with the frozen sections. A counterstain highlighted the epithelium. RESULTS: Continuous curvilinear capsulorrhexis was successfully and easily completed in all cases without any complications. Frozen section analysis using light microscopy demonstrated accumulation of trypan blue dye in the basement membrane of the lens capsule. Staining was concentrated in the portion of the membrane adjacent to the lens epithelium. The lens epithelium could not be clearly identified on the frozen sections. Consequently, immunohistochemical analysis with markers for type IV collagen was performed. A counterstain highlighted the epithelium. This confirmed that the layer staining with trypan blue was the basement membrane, a consistent feature on all the specimens. CONCLUSION: Trypan blue selectively stains the basement membrane of the anterior lens capsule. There is a concentration of dye in the basement membrane adjacent to the lens epithelial cell layer. The lens cortex does not appear clinically to stain with trypan blue. This enables surgeons to distinguish the lens capsule from the cortex and provides sufficient contrast for successful completion of continuous curvilinear capsulorrhexis during cataract surgery.

Basement Membrane↗
PubMed2004

Alpha-lipoic acid increases Na+K+ATPase activity and reduces lipofuscin accumulation in discrete brain regions of aged rats.

A convincing link between oxidative stress and neurodegenerative diseases has been found with the knowledge that it actually damages neuronal cells in culture. We analyzed the effect of DL-alpha-lipoic acid on lipofuscin and Na(+)K(+) ATPase in discrete brain regions of young and aged rats. In aged rats, the level of lipofuscin was increased, and the activity of Na(+)K(+)ATPase was decreased. Intraperitoneal administration of lipoic acid to aged rats led to a duration-dependent reduction and elevation in lipofuscin and enzyme activity, respectively, in the cortex, cerebellum, striatum, hippocampus, and hypothalamus of the brain. These results suggest that lipoic acid, a natural metabolic antioxidant, should be useful as a therapeutic tool in preventing neuronal dysfunction in aged individuals.

Aging↗
PubMed1981

New developments in our knowledge of blood pressure regulation.

This paper reviews recent information about neural and humoral control of arterial blood pressure. Considerable evidence is accumulating in support of the concept that neural and humoral systems interact at both central and peripheral sites to modulate arterial pressure and to participate in the mechanisms of hypertension. The neural mechanisms reviewed include reflexes originating from sinoaortic receptors, and afferents arising from the kidney. Humoral agents discussed include angiotensin and vasopressin and the participation of their central and peripheral actions in the pathogenesis of hypertension.

Angiotensin II↗
PubMed2003

Proteolytic 'defences' and the accumulation of oxidized polypeptides in cataractogenesis and atherogenesis.

Over the last few years, it has been clearly established that normal plasma contains low levels of oxidized polypeptides, and that these accumulate in tissues during several age-related pathologies. In contrast, normal mammalian aging, contrary to conventional dogma, is not clearly associated with enhanced levels of oxidized proteins, except in extracellular connective tissues, whose proteins can, for example, be oxidized by the neutrophil oxidative burst. Since mildly oxidized proteins are susceptible to accelerated degradation in most experimental systems, the question arises as to how the accumulation of oxidized proteins can take place. Such accumulation requires an excess of production (or deposition) over removal, which might reflect alterations in capacity or rate of production or removal. This chapter discusses our presently limited knowledge of rates and control of proteolysis of oxidized proteins in two pathologies, cataractogenesis and atherogenesis. It commences with a brief summary of current understanding of the mechanisms of protein oxidation, and of the observed accumulation of oxidized proteins in several pathologies.

Arteriosclerosis↗
PubMed2006

Intestinal gases and flatulence: possible causes of occurrence.

All gases entrapped in closed body cavities are destined to be partially or completely absorbed. Intestinal gases often accumulate and cause flatulence. This paper proposes a simple concept of intestinal gas occurrence based on our knowledge on gas resorption in other body cavities. Compliance of intestinal and abdominal walls makes pressure in the liquid chyme bubbles near 760 mmHg. Intestinal gases are from three sources. Air can be swallowed, CO2 come from the gastric acid neutralisation and from intestinal bacterial colonies that also produce hydrogen and methane. In continuously mixed liquid chyme, the total pressure of blood gases is similar or lower than in the venous blood ( or=760 mmHg). Some local production of bacterial gases with partial pressure of more than 90 mmHg is required, so the resulting small bowel bubbles would contain less than 20% of bacterial gases. If peristaltic mixing of chyme is prevented by an obstacle, local pressures of bacterial gases build up, form bubbles that fuse and finally make X-ray visible aeroliquid levels. Bacterial gases make almost 3/4 of the flatulence. Formation of bubbles destined to become flatulence might depend on altered rheological condition of the large bowel content, with local abundant production of bacterial gases near bacterial colonies. Gases are unable to diffuse rapidly through the dense liquid content and local accumulation allows formation of bubbles mainly of bacterial gases. Their pressure can be higher 760 mmHg, since they are stretching the thick content. Poor diffusion of gases keeps them almost free of blood gases and their entrance makes them bigger. As the content moves along the colon, the content is becoming more solid and gases are becoming entrapped in large bubbles. Some blood and bacterial gases are absorbed and exhaled, but the remaining quantity has no other escape except flatulence. Flatulence rich in bacterial gases might be the price for the large bowel water reabsorption. It seems that beside the peroral use of antibiotics active in the colon, little can be done to reduce flatulence.

Bacteria↗
PubMed1988

Problem-solving skills, solving problems and problem-based learning.

This paper reviews the empirical evidence in support of the three concepts in the title. To the extent that a skill should be a general strategy, applicable in a variety of situations, and independent of the specific knowledge of the situation, there is little evidence that problem-solving skills, as described and measured in medical education, possess these characteristics. Instead there is an accumulation of evidence that expert problem-solving in medicine is dependent on (I) a wealth of prior specific experiences which can be used in routine solution of problems by pattern recognition processes, and (2) elaborated conceptual knowledge applicable to the occasional problematic situation. The use of problem-based learning (PBL) as an educational strategy is explored. In particular, the evidence suggesting the compatibility of PBL with this theory of expertise is discussed. Finally, I review some issues in the design of PBL curricula from the perspective of the proposed model of expertise.

Clinical Competence↗
PubMed2003

Temperature-dependent effects of cadmium on Daphnia magna: accumulation versus sensitivity.

Standard toxicity tests are performed at one constant, optimal temperature (usually 20 degrees C), while in the field variable and suboptimal temperatures may occur. Lack of knowledge on the interactions between chemicals and temperature hampers the extrapolation of laboratory toxicity data to ecosystems. Therefore, the aim of this study was to analyze the effects of temperature on cadmium toxicity to the waterflea Daphnia magna and to address possible processes responsible for temperature-dependent toxicity. This was investigated by performing standard toxicity tests with D. magna under a wide temperature range. Thermal effects on accumulation kinetics were determined by estimating uptake and elimination rates from accumulation experiments. To study temperature dependency of the intrinsic sensitivity of the daphnids to cadmium, the DEBtox model was used to estimate internal threshold concentrations (ITCs) and killing rates from the toxicity and accumulation data. The results revealed that increasing temperature lowered the ITC and increased the killing rate and the uptake rate of the metal. Enhanced sensitivity of D. magna was shown to be the primary factor for temperature-dependent toxicity. Since temperature has such a major impact on toxicity, a temperature correction may be necessary when translating toxicity data from the laboratory to the field.

Animals↗
PubMed1989

Sodium-coupled ion cotransport and the volume regulatory increase response.

In conclusion, maintenance of volume homeostasis is a fundamental requirement of all cells. For many cell types, this process requires expression of ion cotransport mechanisms as well as accumulation of osmotically-active organic compounds. Recent observations have indicated that the cellular mechanisms responsible for modulating hypertonic volume regulation are complex and appear to involve hormonal, biochemical and physico-chemical stimuli. Knowledge of the specific ion-transport mechanisms involved in the initial phase of VRI, the factors that control their expression, and the interrelationships between inorganic and organic solute accumulation will be required before an in depth understanding of hypertonic cell volume regulation in medullary nephron segments can be achieved.

Animals↗
PubMed2002

Expression and accumulation of lumican protein in uterine cervical cancer cells at the periphery of cancer nests.

Lumican is a member of a small leucine-rich proteoglycan (SLRP) family and is reported to be overexpressed during the wound healing process of the cornea, and ischemic and reperfused heart. In the carcinomatous tissues, lumican is overexpressed in human breast and pancreatic cancer tissues. In the present study, we aimed to clarify the expression of lumican mRNA and its protein in human cervical cancer cell lines (CaSki, ME-180 and HeLa cells) and their localization in normal and cancerous human cervical tissues. Reverse transcription-polymerase chain reaction and Western blot analysis revealed the expression of lumican mRNA and its protein in CaSki, ME-180 and HeLa cells. No or weak immunoreactivity of the lumican protein was observed in stroma but not in squamous and ductal cells of non-cancerous uterine cervical tissues. In 21 of 28 (75%) cervical cancer cases, the lumican protein was strongly expressed in cancer cells, and accumulated particularly in cancer cells at the periphery of the cancer nests. It was also expressed in the fibroblasts adjacent to the cancer cells. In situ hybridization analysis revealed that lumican mRNA was not expressed in squamous or ductal epithelial cells in non-cancerous tissues, but was expressed in most cancer cells and stromal fibroblasts in uterine cervical cancer tissues. The lumican protein was not localized in normal squamous or ductal cells close to cancer cells, but its mRNA was strongly expressed in the same cells. To our knowledge, this is the first report on lumican synthesized by squamous cell carcinomas. These findings may indicate that the accumulated lumican protein in cancer cells at the periphery of cancer nests may play roles in the growth or invasion of human cervical cancer cells.

Blotting, Western↗
PubMed2001

The cytoplasmic escape and nuclear accumulation of endocytosed and microinjected HPMA copolymers and a basic kinetic study in Hep G2 cells.

The development of macromolecules as drugs and drug carriers requires knowledge of their fate in cells. To this end, we studied the internalization and subcellular Fate of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers in Hep G2 (human hepatocellular carcinoma) cells. Semiquantitative fluorometry confirmed that galactose was an effective ligand for receptor-mediated endocytosis for Hep G2 cells. The rate of internalization of a galactose-targeted copolymer was almost 2 orders of magnitude larger than that of the nontargeted copolymer. Confocal fluorescent microscopy of both fixed and live cells revealed that the polymer entered the cells by endocytosis. After longer incubation times (typically >8 hours), polymer escaped from small vesicles and distributed throughout the cytoplasm and nuclei of the cells. Polymer that entered the cytoplasm tended to accumulate in the nucleus. Microinjection of the HPMA copolymers into cells' cytoplasm and nuclei indicated that the polymers partitioned to the nucleus. The data from fixed cells was confirmed by microscopy of live, viable cells. To examine the effect of the fluorescent dye on the intracellular fate, polymers with fluorescein, Oregon Green 488, Lissamine rhodamine B, and doxorubicin were tested; no significant differences were observed.

Acrylamides↗
PubMed2000

Undergraduate medical education: tendencies and requirements in a rapidly developing Europe.

This study pinpoints the necessity to constantly monitor local approaches in undergraduate medical education on an inter-European scale. Traditional undergraduate medical curricula need restructuring to account for the increasing amount of medical knowledge and rapid changes and developments in societies, nosology, therapy and IT. European undergraduate medical curricula should be harmonized not egalized, with a focus on inter-European sharing of resources, mobility, credit (allocation, accumulation and transfer), definition of European and trans-European mission statements, identification of quality metrics, advice on dealing with conflicting aims such as specialization and generalization, on communicating core knowledge instead of providing overabundance of information, and on introducing multifaceted teaching and learning methods, as well as providing strategies for life long learning. Sound medical education can no longer and nowhere be considered under the autonomous auspices of individual Medical Schools or national philosophies. It has to be perceived and structured as a competitive and flexible approach which promotes life long learning of teachers, students, physicians and other related staff with international awareness. It is stressed that student and staff mobility, as well as virtual mobility in the form of worldwide available teaching modules and expertise have to be incorporated into national medical curricula. This is to guarantee up-to-date education in support of patient demands, future professionality and competitiveness of students, physicians and Public Health System institutions. The formal approaches of traditional subject related curricula as well as problem based learning must be linked with quality approved state of the art ODL, evaluated international CME strategies and training in the utilization of IT in preparation of lifelong learning. Strategies for the use of IT need updating on a regular basis to diminish the gap between undergraduate and postgraduate medical education. General European perspectives of medical education are discussed in relation to ECTS, ODL, compulsory credited and evaluated CME and relicensing of physicians. Prime features of ETM--the most reputed and well-known European medical CME initiative fostering quality assured international awareness are described and recommended for local and nationwide implementation. Specific links of the Bonn undergraduate medical curriculum with credited and evaluated CME and imminent European strategies are detailed. The authors conclude that European universities not adapting at least some of the outlined curricular necessities will rapidly lose their competitiveness compared to other national and international Medical Schools. Harmonized European ethical mission statements and consequent utilization of IT deserve special considerations in this context.

Computer-Assisted Instruction↗
PubMed2006

Spatio-temporal accumulation of microRNAs is highly coordinated in developing plant tissues.

MicroRNAs (miRNAs) are an abundant class of small, endogenous non-protein-coding RNAs, approximately 21 nucleotides in length, that modulate the expression of animal and plant target genes at the post-transcriptional level. Recent work has shown that miRNA-based gene regulation plays a crucial role in pathways involved in plant growth and development. However, knowledge about the timing and spatial regulation of plant miRNA expression is still limited. Here we used in situ analysis to demonstrate that miRNAs accumulate spatially and temporally in a highly restricted manner in Nicotiana benthamiana and Arabidopsis thaliana. The presence of the seven investigated miRNAs was characteristic of the developing organs, implying a role in cell-fate establishment, differentiation and cell-cycle progression. Spatial analyses revealed that six of the studied miRNAs were present in vascular bundles, suggesting that mobile miRNAs in the phloem could contribute to the coordination of organogenesis and development. The obvious absence of miR167 in vascular bundles represented an exception to this observation, implying an active process in regulating the presence of miRNAs in the vascular system. Taken together, our results imply that the spatially and temporally organized accumulation of miRNAs plays a pivotal role in fine-tuning of target gene expression in plant development.

Arabidopsis↗
PubMed1999

Knowing in the context of acting: the task dynamics of the A-not-B error.

The A-not-B error is one of the most robust and highly studied phenomena in developmental psychology. The traditional Piagetian interpretation is that the error reflects the immaturity of infants' understanding of objects as permanent entities. More recently, the error has been interpreted in terms of changes in representation, in memory, in spatial knowledge, and in inhibitory processes. Each account may be partially right but none offers a unified account of the many accumulated facts about this error. This article presents and tests a new unified explanation. The authors propose that the perseverative reach back to A is the product of the processes that take a hand to a location in visual space: the body-centered nature of the spatial code, memories for previous reaching activity, and the close coupling of looking and reaching. The results from 6 experiments support this explanation. The results are used to challenge the idea of knowledge independent of and distinct from behavior.

Analysis of Variance↗
PubMed1979

[Chromium--its community hygienic importance].

The present contribution is a literature survey of the presentday knowledge of the chromium contamination of the biosphere. It gives an insight into the absorption mechanism, accumulation and toxicity of chromium in man, and deals with its tolerance. Preliminary investigations into the chromium distribution and burden in the territory of the GDR are presented.

Chromium↗
PubMed2003

Jellyfish green fluorescent protein as a useful reporter for transient expression and stable transformation in Medicago sativa L.

The aim of the experiments reported herein was to transiently test different gene constructs using green fluorescent protein (GFP) as a reporter gene for a future localization of the maize beta-zein in the chloroplast of alfalfa ( Medicago sativa L.). The transient expression of two GFP genes was compared in alfalfa leaves to determine which of these two mutants is the easier to detect. Based on the intensity of fluorescence emitted, the GFP S65C gene was used to assemble a chloroplast-targeted GFP to verify the efficiency of the transit peptide for chloroplast targeting. A chloroplast-targeted fusion protein between beta-zein and GFP was then assembled, and this protein was observed to accumulate in small aggregates into the chloroplasts of transiently transformed cells. To the best of our knowledge, this is the first report of the GFP S65C gene being used to obtain transformed alfalfa plants expressing GFP.

Chloroplasts↗
PubMed2004

The anaphylatoxins bridge innate and adaptive immune responses in allergic asthma.

The complement system has long been recognized for its role as a lytic effector system that protects against microbial pathogens, as well as for its role in mediating acute and chronic inflammatory responses. Many of the inflammatory sequelae of complement activation can be related to the complement cleavage fragments C3a and C5a, the so-called anaphylatoxins (ATs). Cloning and subsequent gene targeting of their corresponding receptors, as well as generation of specific C3a and C5a inhibitors, have fueled new interest in studies aimed at defining the roles of the anaphylatoxins in inflammatory diseases. Traditionally, the anaphylatoxins have been considered mediators of end-stage effector mechanisms. However, recent data from animal models of allergic asthma suggest that C3a and C5a provide a critical link between innate and adaptive immunity. This review is aimed at outlining our current knowledge of when and where anaphylatoxins contribute to and control the development of allergic asthma. The accumulated data suggest a model in which C3a and C5a play important but opposing roles during allergen-induced T-cell polarization: C3a promotes Th2 responses, whereas C5a prevents Th2 polarization. During the effector phase, both anaphylatoxins trigger the inflammatory response and contribute to bronchoconstriction.

Allergens↗
PubMed2006

The role of the NKG2D receptor for tumor immunity.

Natural killer (NK) cells have originally been identified based on their capacity to kill transformed cells in a seemingly non-specific fashion. Over the last 15 years, knowledge on receptor ligand systems used by NK cells to specifically detect transformed cells has been accumulating rapidly. One of these receptor ligand systems, the NKG2D pathway, has received particular attention, and now serves as a paradigm for how the immune system is able to gather information about the health status of autologous host cells. In addition to its significance on NK cells, NKG2D, as well as other NK cell receptors, play significant roles on T cells. This review aims at summarizing recent insights into the regulation of NKG2D function, the control over NKG2D ligand expression and the role of NKG2D in tumor immunity. Finally, we will discuss first attempts to exploit NKG2D function to improve immunity to tumors.

Animals↗