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Biomedical subjects

A Ring

Publications and source records attributed to A Ring.

At least 19 recordsLinked to original sources

Analysis of biodegradation of copolymer dermis substitutes in the dorsal skinfold chamber of balb/c mice.

PEGT/PBT-block-copolymer dermis substitutes were inserted into dorsal skinfold chambers of balb/c mice (n=36). Scaffolding matrices with 3 different pore diameters (pore diameter: <75 micro m, 75-212 micro m and 250-300 micro m) were analyzed on days 7, 14, and 21 post implantation by scanning electron and light microscopy. The quantification of matrix fragmentation was performed using image-analytical software analySIS(R). The fragmentation rate in scaffolding matrices with a pore size of < 75 micro m was observed to be higher than in matrices of larger pore sizes. Image-analytical evaluation over 21 days revealed a reduction of the copolymer matrix by approximately 32% for the <75 micro m matrices, 23% for the 75-212 micro m matrices and 18% for the matrices, where pore size ranged between 250 micro m and 300 micro m. Twenty-one days after implantation, the matrix pores of 75-212 micro m and 250-300 micro m scaffolds were totally filled by vascularized fibrous tissue. Contrarily, an increased formation of foreign-body giant cells was observed in matrices with pore size <75 micro m. The pore size of the scaffolding PEGT/PBT dermis substitutes affects their degradative behaviour in vivo.

Animals↗

Mid-infrared spectroscopy on skin using a silver halide fibre probe in vivo.

BACKGROUND/AIM: Mid-infrared spectroscopy is a versatile method for in vivo investigation of skin after topical treatment with skin care products. METHODS: FTIR-spectrometer (Bruker Optics) with a flexible silver halide fibre probe (Infrared Fiber Sensors). RESULTS: Absorbance spectra from 700 to 3000 cm(-1) have been recorded to gain information about proteins (amide-I and amide-II vibrations at 1650 and 1550 cm(-1)), esters (1740 cm(-1)), carboxylic acid (1710 cm(-1)), polyalcohols (1050 cm(-1)) and hydrocarbons (CH(n) vibrations at 2800-3000 cm(-1)). CONCLUSIONS: Using the particular light guide, we were able to measure for the first time the effects of lip care products on lips directly. Furthermore, water binding and glycerol content of the skin could be determined simultaneously, as well as the replenishment of lipids by lipid-enriched bath oil.

Adolescent↗

Neuroprotective effects of inhibiting N-methyl-D-aspartate receptors, P2X receptors and the mitogen-activated protein kinase cascade: a quantitative analysis in organotypical hippocampal slice cultures subjected to oxygen and glucose deprivation.

Cell death was assessed by quantitative analysis of propidium iodide uptake in rat hippocampal slice cultures transiently exposed to oxygen and glucose deprivation, an in vitro model of brain ischemia. The hippocampal subfields CA1 and CA3, and fascia dentata were analyzed at different stages from 0 to 48 h after the insult. Cell death appeared at 3 h and increased steeply toward 12 h. Only a slight additional increase in propidium iodide uptake was seen at later intervals. The mitogen-activated protein kinases extracellular signal-regulated kinase 1 and extracellular signal-regulated kinase 2 were activated immediately after oxygen and glucose deprivation both in CA1 and in CA3/fascia dentata. Inhibition of the specific mitogen-activated protein kinase activator mitogen-activated protein kinase kinase by PD98059 or U0126 offered partial protection against oxygen and glucose deprivation-induced cell damage. The non-selective P2X receptor antagonist suramin gave neuroprotection of the same magnitude as the N-methyl-D-aspartate channel blocker MK-801 (approximately 70%). Neuroprotection was also observed with the P2 receptor blocker PPADS. Immunogold data indicated that hippocampal slice cultures (like intact hippocampi) express several isoforms of P2X receptors at the synaptic level, consistent with the idea that the effects of suramin and PPADS are mediated by P2X receptors. Virtually complete neuroprotection was obtained by combined blockade of N-methyl-D-aspartate receptors, P2X receptors, and mitogen-activated protein kinase kinase. Both P2X receptors and N-methyl-D-aspartate receptors mediate influx of calcium. Our results suggest that inhibition of P2X receptors has a neuroprotective potential similar to that of inhibition of N-methyl-D-aspartate receptors. In contrast, our comparative analysis shows that only partial protection can be achieved by inhibiting the extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase cascade, one of the downstream pathways activated by intracellular calcium overload.

Animals↗

Comparison of electrical thresholds for evoking movements from sensori-motor areas of the cat cerebral cortex and its relation to motor training.

Motor maps and electrical thresholds for evoking movements from motor areas of the cerebral cortex were evaluated in normal cats by using intracortical microstimulation techniques. Stainless steel chambers were implanted over craniotomies in adult cats trained to perform reaching and retrieval movements with their forelimbs. Prehensile motor training was continued and movement performance monitored for about 6-10 weeks during which the cortex was progressively explored with sharp tungsten electrodes inserted into cortical gyri (anterior and posterior sigmoid, and coronal) and the banks of sulci (cruciate, presylvian and coronal). Twice weekly, under light general anaesthesia, 3-4 tracks were made in either hemisphere till about 50 tracks were made in each hemisphere. Mean thresholds for evoking forelimb movements from different cytoarchitectonic areas (4gamma, 4delta, 6agamma and 3a) were compared and no consistent or significant differences were observed between the different areas. In the animals (4/6) which used either forelimb to perform the tasks, there were no consistent differences in the mean thresholds for evoking forelimb movements from the two hemispheres. However, in 2 animals, which used their right forelimbs predominantly or exclusively to perform all the tasks, mean thresholds for evoking forelimb movements was significantly higher in areas 4gamma and 6agamma of the left hemisphere (compared to the right); no consistent differences in the mean thresholds for evoking hindlimb or facial movements were observed between the two hemispheres. These findings suggest that ICMS thresholds for evoking forelimb movements may be similar in different sensorimotor areas of the cat cerebral cortex, and these thresholds could be influenced by motor training.

Animals↗

Changes in electrical thresholds for evoking movements from the cat cerebral cortex following lesions of the sensori-motor area.

We evaluated motor maps in the cerebral cortex and motor performance in cats before and after lesions of the forelimb representation in the primary motor area. After the lesion there was a reduction in the use of the affected forelimb and loss of accuracy in prehension tasks using the forelimb; some recovery occurred during the mapping study. Electrode tracts and lesion sites were located in cytoarchitectonically identified cortical areas 4gamma, 4delta, 6aalpha, 6agamma, 3a. The lesions were mainly in area 4gamma. In the lesioned hemisphere there were many points around the lesion site (in areas 4gamma and 3a) from which movements could not be evoked. In some areas distant from the lesion site (e.g. area 6agamma) the mean thresholds for evoking forelimb movements were significantly elevated. Mean thresholds for evoking hindlimb and facial movements were not different from before. In the contralateral hemisphere mean thresholds for evoking forelimb, but not hindlimb or facial movements, were significantly elevated in several sensorimotor areas (area 4gamma, 6agamma and 3a). Mean thresholds for evoking forelimb movements appeared to progressively increase during the time of study. Minimal currents required to evoke forelimb movements from the cerebral cortex increase (possibly progressively) following a lesion of the forelimb representation in the primary motor area, affecting many interconnected motor areas in the hemispheres ipsilateral and contralateral to the lesioned site. This increase in thresholds may play a role in the changes in cortical control of the affected and contralateral limbs following brain lesions and explain the increased sense of effort required to produce movements.

Animals↗

Is surgery necessary after complete clinical remission following neoadjuvant chemotherapy for early breast cancer?

PURPOSE: This retrospective analysis aimed to identify whether breast cancer patients receiving radiotherapy alone following a complete clinical remission (cCR) to neoadjuvant chemotherapy had a worse outcome than those treated with surgery. PATIENTS AND METHODS: One hundred thirty-six patients who had achieved a cCR to neoadjuvant chemotherapy for early breast cancer were identified from a prospectively maintained database of 453 patients. Of these, 67 patients had undergone surgery as their primary locoregional therapy, and 69 patients had radiotherapy alone. Outcome was assessed in relation to local recurrence-free survival, disease-free survival, and overall survival. RESULTS: Median follow-up was 63 months in the surgery group and 87 months in the no surgery group. Prognostic characteristics were well balanced between the two groups. For surgery and no surgery, respectively, there were no significant differences in disease-free survival or overall survival (5-year, 74% v 76%; 10-year, 60% v 70%, P =.9) between the two groups. There was a nonsignificant trend toward increased locoregional-only recurrence for the no surgery group (21% v 10% at 5 years; P =.09), but no long-term failures of local control. Patients in the no surgery group who also achieved an ultrasound complete remission had a 5-year local recurrence rate of only 8%. CONCLUSION: In patients achieving a cCR to neoadjuvant chemotherapy, radiotherapy alone achieve survival rates as good as with surgery, but with higher local recurrence rates. Ultrasound may identify a low recurrence rate subgroup for assessing no surgery in a prospective trial.

Adult↗

Self-reported leisure-time physical activity during pregnancy and relationship to psychological well-being.

The psychological benefits of physical exercise have been reported in numerous populations. While studies have found elevated stress and depressed mood during pregnancy and no adverse birth effects associated with low to moderate intensity exercise, few have examined exercise in relation to psychosocial outcomes during pregnancy. The present study examined leisure-time physical activity (LTPA) patterns during pregnancy and its association to psychological well-being. In each trimester of pregnancy 180 women self-reported on frequency, form and duration of LTPA through structured interviews. Beginning in the third month of pregnancy, data was collected monthly on depressed mood (Lubin depression adjective checklist), state-anxiety, pregnancy-specific stress (pregnancy experiences questionnaire) and Hassles Scale. Independent samples t-tests comparing exercisers and non-exercisers in each trimester showed exercisers reported significantly less depressed mood, daily hassles, state-anxiety and pregnancy-specific stress in the first and second trimester. Women who exercised in the third trimester reported less state-anxiety in that trimester compared to non-exercisers. The results indicate a consistent association between enhanced psychological well-being, as measured by a variety of psychosocial inventories, and LTPA participation particularly during the first and second trimesters of pregnancy. In healthy pregnant women, even low-intensity regular exercise may be a potentially effective low-cost method of enhancing psychological well-being.

Adaptation, Psychological↗

A new concept of cellular uptake and intracellular trafficking of long-chain fatty acids.

Fatty acids are the main structural and energy sources of the human body. Within the organism, they are presented to cells as fatty acid:albumin complexes. Dissociation from albumin represents the first step of the cellular uptake process, involving membrane proteins with high affinity for fatty acids, e.g., fatty acid translocase (FAT/CD 36) or the membrane fatty acid-binding protein (FABPpm). According to the thus created transmembrane concentration gradient, uncharged fatty acids can flip-flop from the outer leaflet across the phospholipid bilayer. At the cytosolic surface of the plasma membrane, fatty acids can associate with the cytosolic FABP (FABP(c)) or with caveolin-1. Caveolins are constituents of caveolae, which are proposed to serve as lipid delivery vehicles for subcellular organelles. It is not known whether protein (FABP(c))- and lipid (caveolae)-mediated intracellular trafficking of fatty acids operates in conjunction or in parallel. Channeling fatty acids to the different metabolic pathways requires activation to acyl-CoA. For this process, the family of fatty acid transport proteins (FATP 1-5/6) might be relevant because they have been shown to possess acyl-CoA synthetase activity. Their variable N-terminal signaling sequences suggest that they might be targeted to specific organelles by anchoring in the phospholipid bilayer of the different subcellular membranes. At the highly conserved cytosolic AMP-binding site of FATP, fatty acids are activated to acyl-CoA for subsequent metabolic disposition by specific organelles. Overall, fatty acid uptake represents a continuous flow involving the following: dissociation from albumin by membrane proteins with high affinity for fatty acids; passive flip-flop across the phospholipid bilayer; binding to FABP(C) and caveolin-1 at the cytosolic plasma membrane; and intracellular trafficking via FABP(c) and/or caveolae to sites of metabolic disposition. The uptake process is terminated after activation to acyl-CoA by the members of the FATP family targeted intracellularly to different organelles.

Animals↗

[Chicken bones in the uterus--an exceptional reason for sterility].

Chicken bones in the uterus - an exceptional reason for sterility.Because of a substantial increase in the migration from developing countries to Europe, gynaecologists have to face more the fact, that they are confronted more frequently both with medical and social problems from these regions. WE present the following case: In 1999 a Congolese women was referred to our clinic because of sterility of unknown reason. The hysteroscopy followed by D & C showed chicken bones in the uterus. It can be assumed, that a clandestine abortion performed in her native land is the reason for this finding.

Abortion, Illegal↗

Fatty acid transporters in plasma membranes of cardiomyocytes in patients with dilated cardiomyopathy.

BACKGROUND: Long-chain fatty acids are one of the major cardiac energy substrates. Although the exact mechanism of myocardial fatty acid uptake is not known, several proteins, including the integral membrane proteins FATP1 (fatty acid transport protein 1) and FAT (fatty acid translocase), are being implicated in this process. The aim of this study was to further investigate FATP1 and FAT in the heart and its potential role in myocardial fatty acid utilization. - METHODS: The expression of FATP1 and FAT in mouse myocardium and in myocardial biopsies of 14 patients with different cardiomyopathies was detected by immunocytochemistry and visualized with a laser scanning microscope. - RESULTS: FAT and FATP1 are co-expressed on the plasma membrane of cardiac endothelial cells and on the sarcolemma of cardiomyocytes. The staining-pattern and the intensity of signal for both transport proteins was constant in different cardiomyopathies compared with the expression in biopsies of patients with other cardiac diseases and the expression in the myocardium of healthy mice. - CONCLUSION: Cardiac endothelial cells and cardiomyocytes express FAT and FATP1 in vivo, suggesting an active part of these proteins in the uptake process of long-chain fatty acids. However, we did not find evidence for an altered expression of fatty acid transport proteins in patients with dilated cardiomyopathy, suggesting that these proteins are of minor importance in this kind of heart failure.

Adult↗

Group B streptococcal beta-hemolysin induces nitric oxide production in murine macrophages.

Group B streptococcus (GBS) is the leading cause of sepsis in neonates. Nitric oxide (NO) release plays a role in the hypotension that characterizes septic shock. To examine the role of the GBS beta-hemolysin in NO production, the murine macrophage line RAW 264. 7 was exposed to a wild-type (WT) GBS isolate and to hyperhemolytic (HH) and nonhemolytic (NH) transposon mutants derived from that isolate. After activation of macrophages by the WT strain, the HH mutant, or cell-free extracts of beta-hemolysin, nitrite release into the supernatant increased >10-fold and inducible NO synthase (iNOS) levels in cell lysates increased up to 10-fold compared with treatment with the NH mutant or extracts from that mutant. Hemolysin-induced NO production was dependent on protein tyrosine kinases and NF-kappaB, but not on extracellular signal-related kinase-1/2-mitogen-activated kinases or protein kinase A. These results indicate that GBS beta-hemolysin induces murine macrophage iNOS via intracellular pathways similar to those that mediate lipopolysaccharide-induced iNOS activation.

Animals↗

Growth hormones reverse desensitization of P2Y(2) receptors in rat mesangial cells.

Rat glomerular mesangial cells (GMC) express P2Y(2) purinoceptors and respond to nucleotide stimuli with a transient increase in the cytosolic Ca(2+) concentration and the receptors desensitize upon repeated stimulation with nucleotide. We demonstrate that there is a cross-talk from the signaling of tyrosine kinase to P2Y(2) receptors. For most cells repeated applications of ATP completely abolished the response, as did activation of PKC with 500 nM PMA. In contrast, preincubation with the PKC inhibitor chelerythrine (100 nM) prevented desensitization. Desensitization after application of ATP was reversed by subsequent incubation with PDGF-BB (50 ng/ml) or insulin (660 mU/ml). We conclude that the desensitization is caused by phosphorylation due to PKC and is under the control of growth factors. The findings support the hypothesis that growth hormones potentiate nucleotides as proinflammatory mediators and we hypothesize that they have bearing on the hyperfiltration seen in diabetes.

Adenosine Triphosphate↗

Anxiety among Israeli soldiers during the Gulf War.

The impact of stress was investigated among Israeli soldiers during the Gulf War. The study included 40 healthy young adults in active service. Their scores on the Hamilton Anxiety Rating Scale were evaluated during the first week of the war. Our subjects were divided into two equal sub-groups (N=20); combatants and auxiliary personnel. Higher levels of anxiety were found among the combatants. Factor analysis revealed three differing factors: arousal symptoms, numbing and distraction. We discuss the possible explanations for these differences.

Adolescent↗

Sensitivity of empirical metrics of rate of absorption in bioequivalence studies.

PURPOSE: The sensitivity and effectiveness of indirect metrics proposed for the assessment of comparative absorption rates in bioequivalence studies [Cmax, Tmax, partial AUC (AUCp), feathered slope (SLf), intercept metric (I)] were originally tested by assuming first-order absorption. The present study re-evaluates their sensitivity performances using the more realistic inverse Gaussian (IG) model characterizing the input process for oral drug administration. METHODS: Simulations were performed for both the first-order or exponential model (EX) which is determined by only one parameter, the mean absorption time (MAT = 1/k(a)), and the IG model, which additionally contains a shape parameter, the relative dispersion of absorption time distribution (CV2A). Kinetic sensitivities (KS) of the indirect metrics were evaluated from bioequivalence trials (error free data) generated with various ratios of the true parameters (MAT and CV2A) of the two formulations. RESULTS: The behavior of the metrics was similar with respect to changes in MAT ratios with both models: KS was low with Cmax, moderate with SLf and AUCp, and high with I and Tmax following correction for apparent lag time (Tlag). Changes of the shape parameter CV2A, however, were not detectable by Cmax, Tmax, SLf, and AUCp. Changes in both MAT and CV2A were well reflected by I with CV2A - ratio > 1. I exhibited approximately full KS also with CV2A - ratio < 1 when a correction was first applied for the apparent lag time. CONCLUSIONS: The time profile of absorption rates is insufficiently characterized by only one parameter (MAT). Indirect metrics which are sensitive enough to detect changes in the scale and shape of the input profile could be useful for bioequivalence testing. Among the tested measures, I is particularly promising when a correction is applied for Tlag.

Antipsychotic Agents↗

Renal NO production and the development of hypertension.

The juxtaglomerular apparatus (JGA) has the very important functions of detecting the fluid flow rate to the distal tubule and thus controlling the glomerular filtration rate (GFR) (tubuloglomerular feedback mechanism [TGF]) and renin release from the afferent arteriole. In studies of the TGF it has been evident that the sensitivity of this mechanism can be reset. Volume expansion will reset it to a low sensitivity leading to a high GFR and urine excretion rate, while dehydration will sensitize the TGF mechanism, giving rise to a low GFR and low urine excretion rate. Furthermore, we have found that in animals that spontaneously develop hypertension there is initially a sensitization of the TGF, leading to a reduced GFR and urine excretion rate, with fluid volume retention in the body and a consequent rise in blood pressure. When the pressure is raised, the TGF characteristics are normalized. In the macula densa (MD) cells in the JGA, there is a large production of NO from neuronal NOS. This production continuously reduces TGF sensitivity and is apparently impaired in animals that spontaneously develop hypertension. When we added an nNOS inhibitor to the drinking water for several weeks while measuring blood pressure, we found an increase in blood pressure after 3-4 weeks of treatment. This effect was abolished by a high salt diet. From these investigations, it also appeared as if nNOS-derived NO inhibited renin release. Experiments have also indicated that NO may resensitize inhibited G-protein coupled purinergic receptors.

Animals↗

The hepatic microvascular responses to sepsis.

The liver is believed to play a major role in the initiation of multiorgan failure, the most lethal complication in the clinical course of sepsis. Microbes and their virulence factors enter the hepatic circulation where they first activate sinusoidal endothelial cells and Kupffer cells to produce proinflammatory mediators, including TNF-alpha, IL-1, IL-6, reactive oxygen metabolites, and eicosanoids. These mediators cause not only microbial killing, but also structural and functional liver damage concerning mainly the parenchymal cells. Leukocytes are targeted to the liver sinusoids by chemoattractants and, like platelets, tether to the sinusoidal endothelial cells, which are in a procoagulant state of inflammatory activation. Clogging of the sinusoids by these cells leads to a decrease of blood flow through the sinusoids, which is further aggravated by endothelin-1 effectuating the constriction of hepatic stellate cells in the sinusoids. In contrast, both nitric oxide (NO) and carbon monoxide (CO) act as antagonists of endothelin-1 by mediating relaxation of sinusoidal vessels. By maintaining an adequate sinusoidal perfusion, both NO and CO are hepatoprotective during the early, hyperdynamic phase of sepsis characterized by an increased cardiac output and moderate peripheral vasodilation. However, during the late, hypodynamic phase of sepsis, massive overproduction of NO by the inducible NO synthase leads to circulatory collapse, which inevitably includes breakdown of the liver circulation.

Endothelium, Vascular↗