julilili42/papers huggingface dataset:
104 Hyperbaric oxygen enhances wound lactate production in rats
2008-06-28

Introduction: Healing wounds are characterized by high lactate levels. In the past, the shift to an anaerobic energy metabolism was thought to be the main source for increased lactate concentration. Lactate is also generated by leukocytic NADPH-linked oxygenase using oxygen and glucose as one of its substrates, a mechanism called aerobic glycolysis. We hypothesize that hyperbaric oxygen therapy by increasing oxygen availability enhances wound lactate production by aerobic glycolysis. Material and methods: Four wire mesh wound cylinders (n = 142) were implanted underneath the dorsal skin in each of 36 male Sprague-Dawley rats (312 ± 11 g). Animals were randomized to two groups: The first group (n = 18) received 100% oxygen with 2.1 ATA for 90 minutes twice a day for a total of 7 days. The second group (n = 18) was treated with 21% oxygen with 1 ATA for the same time schedule. Hyperbaric treatments were administered in a hyperbaric chamber designed for small animals. Wound fluid from the cylinders was aspirated between the two treatment cycles at day 2 and 5 and analysed for lactate using a lactate analyser. Additionally, at day 10 (after 2 days of treatment with 21% oxygen in 1 ATA in both groups) lactate concentrations in wound fluid were measured again. Data are expressed as mean ± SD. A p-value <0.05 was considered significant. Results: Wound lactate concentration was significantly increased both in control and hyperbaric rats at day 5 and day 10 compared to day 2 (controls 4.5 ± 1, 5.9 ± 0.8, 6.7 ± 1.2 mmol/l; p = 0.04 and hyperbarics 4.4 ± 1.2, 6.5 ± 1.3, 8.2 ± 1.3 mmol/l; p = 0.01). At day 2 and day 5 there was no significant difference in lactate levels between control and hyperbaric rats. However, at day 10 lactate concentration was significantly higher in the hyperbaric group compared to the control group (6.7 ± 1.2 vs. 8.2 ± 1.3 mmol/l; p = 0.01). Conclusion: This investigation provides evidence for the mechanism of hyperbaric oxygen action since lactate is known to stimulate collagen production and angiogenesis.
Identification of urinary modified nucleosides and ribosylated metabolites in humans via combined ESI-FTICR MS and ESI-IT MS analysis
2008-06-29

The physiological response of the human body to several diseases can be reflected by the metabolite pattern in biological fluids. Cancer, like other diseases accompanied by metabolic disorders, causes characteristic effects on cell turnover rate, activity of modifying enzymes, and RNA/DNA modifications. This results in an altered excretion of modified nucleosides and biochemically related compounds. In the course of our metabolic profiling project, we screened 24-h urine of patients suffering from lung, rectal, or head and neck cancer for previously unknown ribosylated metabolites. Therefore, we developed a sample preparation procedure based on boronate affinity chromatography followed by additional prepurification with preparative TLC. The isolated metabolites were analyzed by ion trap mass spectrometry (IT MS) and Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS). IT MS was applied for LC-auto MS(3) screening runs and MS(n(n=4-6)) syringe pump infusion experiments, yielding characteristic fragmentation patterns. FTICR MS measurements enabled the calculation of corresponding molecular formulae based on accurate mass determination (mass accuracy: 1-5 ppm for external and sub-ppm values for internal calibration). We were able to identify 22 metabolites deriving from cellular RNA metabolism and related metabolic pathways like histidine metabolism, purine biosynthesis, methionine/polyamine cycle, and nicotinate/nicotinamide metabolism. The compounds 1-ribosyl-3-hydroxypyridinium, 1-ribosyl-pyridinium, and 3-ribosyl-1-methyl-l-histidinium as well as a series of ribosylated histamines, conjugated to carboxylic acids at the N(omega)-position were found as novel urinary constituents. The occurrence of the modified nucleosides 2-methylthio-N(6)-(cis-hydroxyisopentenyl)-adenosine, 5-methoxycarbonylmethyl-2-thiouridine, N(6)-methyl-N(6)-threonylcarbamoyladenosine, and 2-methylthio-N(6)-threonylcarbamoyladenosine in human urine is verified for the first time.
Microsurgical management of spinal schwannomas: evaluation of 128 cases
2008-06-30

Object The authors conducted a study to evaluate the clinical characteristics and surgical outcomes in patients with spinal schwannomas and without neurofibromatosis (NF). Methods The data obtained in 128 patients who underwent resection of spinal schwannomas were analyzed. All cases with neurofibromas and those with a known diagnosis of NF Type 1 or 2 were excluded. Karnofsky Performance Scale (KPS) scores were used to compare patient outcomes when examining the anatomical location and spinal level of the tumor. The neurological outcome was further assessed using the Medical Research Council (MRC) muscle testing scale. Results Altogether, 131 schwannomas were treated in 128 patients (76 males and 52 females; mean age 47.7 years). The peak prevalence is seen between the 3rd and 6th decades. Pain was the most common presenting symptom. Gross-total resection was achieved in 127 (97.0%) of the 131 lesions. The nerve root had to be sacrificed in 34 cases and resulted in minor sensory deficits in 16 patients (12.5%) and slight motor weakness (MRC Grade 3/5) in 3 (2.3%). The KPS scores and MRC grades were significantly higher at the time of last follow-up in all patient groups (p = 0.001 and p = 0.005, respectively). Conclusions Spinal schwannomas may occur at any level of the spinal axis and are most commonly intradural. The most frequent clinical presentation is pain. Most spinal schwannomas in non-NF cases can be resected totally without or with minor postoperative deficits. Preoperative autonomic dysfunction does not improve significantly after surgical management.
Immunosuppressive treatment for focal segmental glomerulosclerosis in adults
2008-06-30

Adult patients treated with CSA at an initial dose of 3.5-5 mg/kg/d in two divided doses perhaps in combination with oral prednisolone 0.15 mg/kg/d are more likely to achieve a partial remission of the nephrotic syndrome compared with symptomatic treatment or prednisolone alone. However, there is a probability of deterioration of kidney function due to the nephrotoxic effect of CSA in the long term. For CSA, a larger controlled trial with longer follow-up should be performed to prove the benefit of this regimen not only on proteinuria but also on the preservation of kidney function. Present available data do not support the general use of alkylating substances for the treatment of FSGS in adults.
Partielle Differentialgleichungen
2008-06-30

The workshop differential equations , organised by Tom Ilmanen (ETH Zürich), Reiner Schätzle (Universität Tübingen) and Neil Trudinger (Australian National University Canberra) was held July 22–28, 2007. This meeting was well attended by 50 participants, including 6 females, with broad geographic reprensentation. The program consisted of 19 talks and 3 shorter contributions and left sufficient time for discussions. One focus was the combination of nonlinear partial differential equations and geometric problems. There were talks on monotonicity formulas in presence of degenerate singularities and on estimates of the singular set for branched minimal immersions. One striking new result was the proof of the diffeomorphic sphere theorem by the use of Ricci flow. Many leading experts in the regularity of elliptic and variational problems and in fully nonlinear differential equations occuring in optimal transport and in Hessian equations attended the workshop. Several main contributions were given to this subject. Here, we mention the proof of interior estimates for quadratic Hessian equations in three dimensions, which has been an open problem for several years of similar relevance as the gradient estimates for the minimal surface equation. New results were also presented for the Willmore functional. It was achieved to write the Euler-Lagrange equation in divergence form, and the existence of minimizers in fixed conformal classes with certain energy bounds were obtained. The organisers and the participants are grateful to the Oberwolfach Institute for presenting the opportunity and the resources to arrange this interesting meeting.
Targeting of AKT1 enhances radiation toxicity of human tumor cells by inhibiting DNA-PKcs-dependent DNA double-strand break repair
2008-07-01

Abstract We have already reported that epidermal growth factor receptor/phosphatidylinositol 3-kinase/AKT signaling is an important pathway in regulating radiation sensitivity and DNA double-strand break (DNA-dsb) repair of human tumor cells. In the present study, we investigated the effect of AKT1 on DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activity and DNA-dsb repair in irradiated non-small cell lung cancer cell lines A549 and H460. Treatment of cells with the specific AKT pathway inhibitor API-59CJ-OH (API; 1-5 μmol/L) reduced clonogenic survival between 40% and 85% and enhanced radiation sensitivity of both cell lines significantly. As indicated by fluorescence-activated cell sorting analysis (sub-G1 cells) and poly(ADP-ribose) polymerase cleavage, API treatment or transfection with AKT1-small interfering RNA (siRNA) induced apoptosis of H460 but not of A549 cells. However, in either apoptosis-resistant A549 or apoptosis-sensitive H460 cells, API and/or AKT1-siRNA did not enhance poly(ADP-ribose) polymerase cleavage and apoptosis following irradiation. Pretreatment of cells with API or transfection with AKT1-siRNA strongly inhibited radiation-induced phosphorylation of DNA-PKcs at T2609 and S2056 as well as repair of DNA-dsb as measured by the γ-H2AX foci assay. Coimmunoprecipitation experiments showed a complex formation of activated AKT and DNA-PKcs, supporting the assumption that AKT plays an important regulatory role in the activation of DNA-PKcs in irradiated cells. Thus, targeting of AKT enhances radiation sensitivity of lung cancer cell lines A549 and H460 most likely through specific inhibition of DNA-PKcs-dependent DNA-dsb repair but not through enhancement of radiation-induced apoptosis. [Mol Cancer Ther 2008;7(7):1772–81]
Migration of protoplanets in radiative discs
2008-07-01

\\n Context. In isothermal discs, the migration of protoplanets is directed\\ninwards. For small planetary masses, the standard type I migration\\nrates are so high that this can result in an unrealistic loss of\\nplanets into the stars.\\n Aims. We investigate the planet-disc interaction in non-isothermal discs\\nand analyse the magnitude and direction of migration for an extended\\nrange of planet masses. \\n Methods. We performed detailed two-dimensional numerical simulations of\\nembedded planets including heating/cooling effects as well as\\nradiative diffusion for realistic opacities.\\n Results. In radiative discs, small planets with migrate outwards at a rate comparable to the absolute\\nmagnitude of standard type I migration. For larger masses, the\\nmigration is inwards and approaches the isothermal, type II migration rate.\\n Conclusions. Our findings are particularly important for the first growth phase of\\nplanets and ease the problem of too rapid inward type I migration.\\n
The Evolving Complexity of the Auxin Pathway
2008-07-01

The plant hormone and signaling molecule auxin is a key player during pattern formation, organogenesis, and various physiological processes. Recent discoveries in auxin biology point toward an auxin pathway with a higher complexity than previously anticipated. This prompted us to review this
Ritonavir induces endoplasmic reticulum stress and sensitizes sarcoma cells toward bortezomib-induced apoptosis
2008-07-01

Abstract The biosynthesis of immunoglobulin leads to constitutive endoplasmic reticulum (ER) stress in myeloma cells, which activates the unfolded protein response (UPR). The UPR promotes protein folding by chaperones and increases proteasomal degradation of misfolded protein. Excessive ER stress induces apoptosis and represents a molecular basis for the bortezomib sensitivity of myeloma. Most solid malignancies such as sarcoma, by contrast, are poorly bortezomib sensitive and display low levels of ER stress. We hypothesized that pharmacologic induction of ER stress might sensitize malignancies to bortezomib treatment. We show that the HIV protease inhibitor ritonavir induces ER stress in bortezomib-resistant sarcoma cells. Ritonavir triggered the UPR, decreased the degradation of newly synthesized protein, but did not directly inhibit proteasomal active sites in the therapeutic dose range in contrast to bortezomib. Whereas neither bortezomib nor ritonavir monotherapy translated into significant apoptosis at therapeutic drug levels, the combination strongly increased the level of ER stress and activated PERK, IRE1, and ATF6, synergistically induced CHOP, JNK, caspase-4, and caspase-9, and resulted in &amp;gt;90% apoptosis. In summary, ritonavir increases the level of ER stress induced by bortezomib, which sensitizes bortezomib-resistant cells to bortezomib-induced apoptosis. Ritonavir may therefore be tested clinically to improve the sensitivity of solid malignancies toward bortezomib treatment. [Mol Cancer Ther 2008;7(7):1940–8]
Local therapy and treatment costs of chronic, venous leg ulcers with electrical stimulation (Dermapulse®): A prospective, placebo controlled, double blind trial
2008-07-01

ABSTRACT The purpose of our study was the evaluation of the therapeutic benefit and the economical profit of low‐frequency pulsed current applied to therapy‐resistant venous leg ulcers. We investigated 39 patients in a prospective, placebo‐controlled, double blind study on the effect of low‐frequency pulsed current (Dermapulse ® ) on healing in chronic venous ulcers during a 4‐month course of treatment. All patients had chronic venous ulcers. The following criteria were recorded: ulcer size, pain, capillary density, and transcutaneous oxygen partial pressure. In verum group 3, ulcers healed and ulcer area was reduced significantly. In placebo group two ulcers healed. Ulcer size was reduced significantly in each group (paired test), the difference of ulcer area reduction between the “verum” and the placebo group (unpaired test) was not significant. Capillary density in the ulcer increased in both groups. In verum group, electrical stimulation led to rapid and lasting reduction of pain (unpaired test, p =0.049). By means of the process calculation method for the subgroup of outpatients this treatment method was economically effective. Electrical stimulation seems to be a viable treatment option for therapy‐resistant venous leg ulcers.
Results from an International Simulation Study on Coupled Thermal, Hydrological, and Mechanical Processes near Geological Nuclear Waste Repositories
2008-07-01

As part of the ongoing international DECOVALEX project, four research teams used five different models to simulate coupled thermal, hydrological, and mechanical (THM) processes near waste emplacement drifts of geological nuclear waste repositories. The simulations were conducted for two generic repository types, one with open and the other with back-filled repository drifts, under higher and lower postclosure temperatures, respectively. In the completed first model inception phase of the project, a good agreement was achieved between the research teams in calculating THM responses for both repository types, although some disagreement in hydrological responses is currently being resolved. In particular, good agreement in the basic thermal-mechanical responses was achieved for both repository types, even though some teams used relatively simplified thermal-elastic heat-conduction models that neglected complex near-field thermal-hydrological processes. The good agreement between the complex and simplified process models indicates that the basic thermal-mechanical responses can be predicted with a relatively high confidence level.
Using Atom Mapping Rules for an Improved Detection of Relevant Routes in Weighted Metabolic Networks
2008-07-01

Computational analysis of pathways in metabolic networks has numerous applications in systems biology. While graph theory-based approaches have been presented that find biotransformation routes from one metabolite to another in these networks, most of these approaches suffer from finding too many routes, most of which are biologically infeasible or meaningless. We present a novel approach for finding relevant routes based on atom mapping rules (describing which educt atoms are mapped onto which product atoms in a chemical reaction). This leads to a reformulation of the problem as a lightest path search in a degree-weighted metabolic network. The key component of the approach is a new method of computing optimal atom mapping rules.
Pathogenesis of diabetic macro- and microangiopathy
2008-07-01

Epidemiological investigations reveal that we must expect a rapid increase in cases of diabetes mellitus in the next few years. As a result, vascular complications in the form of macro- and microangiopathy are also expected to arise more frequently. A classical example of macroangiopathy is coronary arteriosclerosis, microangiopathy is exemplified by diabetic nephropathy. In patients suffering from diabetes, macroangiopathy manifests as atherosclerosis like in nondiabetic patients, characterized by formation of plaques that follows in stages but with an accelerated course due to the different risk factors, especially hyper- and dyslipidemia, with cumulative effects. Thus, atherosclerosis in diabetes begins earlier, is more markedly pronounced and progresses more rapidly. The pathogenetic concept is based on an endothelial lesion that occurs as a result of a diabetes-specific, endothelium-damaging parameters. In case of diabetic microangiopathy histologically characterized by a progressive glomerulosclerosis, arteriolosclerosis and interstitial fibrosis hyperglycemia, along with its consecutive and complex processes that induce matrix increase, is considered to be the primary pathogenetically relevant factor involved. Insulin resistance seems to be the major common denominator at the center of both diabetic macroangiopathy and microangiopathy.
Tumor cell dormancy: implications for the biology and treatment of breast cancer
2008-07-01

Despite progress made in the therapy of solid tumors such as breast cancer, the prognosis of patients even with small primary tumors is still limited by metastatic relapse often long after removal of the primary tumor. Therefore, it has been hypothesized that primary tumors shed tumor cells already at an early stage into the blood circulation. A subset of these disseminated tumor cells may persist in a state of so‐called “dormancy”. Based on cell culture and animal models, dormancy can occur at two different stages. Single dormant cells are defined as cells with a lack of proliferation and apoptosis with the cells undergoing cell cycle arrest. The micrometastasis model defines tumor cell dormancy as a state of balanced apoptosis and proliferation of micrometastasis resulting in no net increase of tumor mass. Mechanisms leading to a growth activation of dormant tumor cells and the outgrowth of manifest metastases are not completely understood. Genetic predisposition of the dormant cells as well as immunological and angiogenetic influences of the surrounding environment may contribute to this phenomenon. In this review, we summarize findings on different factors for tumor cell dormancy and potential therapeutic implications that should help to reduce metastatic relapse in cancer patients.
High-frequency dynamics of hybrid oxide Josephson heterostructures
2008-07-01

We summarize our results on Josephson heterostructures Nb/Au/YBa2Cu3Ox that combine conventional (S) and oxide high-Tc superconductors with a dominant d-wave symmetry of the superconducting order parameter(D). The heterostructures were fabricated on (001) and C1 1 20) YBa2Cu3Ox films grown by pulsed laser deposition. The structural and surface studies of the (1 1 20) YBa2Cu3Ox thin films reveal nanofaceted surface structure with two facet domain orientations, which are attributed as (001) and (110)-oriented surfaces of YBa2Cu3Ox and result in S/D(001) and S/D(110) nanojunctions formed on the facets. Electrophysical propertiesof the Nb/Au/YBa2Cu3Ox heterostructures are investigated by the electrical and magnetic measurements atlow temperatures and analyzed within the faceting scenario. The superconducting current-phase relation (CPR)of the heterostructures with finite first and second harmonics is derived from the Shapiro steps, which appearin the I-V curves of the heterostructures irradiated at frequencies up to 100 GHz. The experimental positionsand amplitudes of the Shapiro steps are explained within the modified resistive Josephson junction model,where the second harmonic of the CPR and capacitance of the Josephson junctions are taken into account. Weexperimentally observe a crossover from a lumped to a distributed Josephson junction limit for the size of theheterostructures smaller than Josephson penetration depth. The effect is attributed to the variations of theharmonics of the superconducting CPR across the heterojunction, which may give rise to splintered vortices of magnetic flux quantum. Our investigations of parameters and phenomena that are specific for superconductorshaving d-wave symmetry of the superconducting order parameter may be of importance for applications suchas high-frequency detectors and novel elements of a possible quantum computer.
Behavioural Alterations in Rats Following Neonatal Hypoxia and Effects of Clozapine: Implications for Schizophrenia
2008-07-01

INTRODUCTION: As a consequence of obstetric complications hypoxia has been discussed as a possible factor in the pathophysiology of schizophrenia. The present study investigated the effects of weak chronic neonatal hypoxia in rats on different behavioural animal models of schizophrenia. METHODS: (1) After neonatal hypoxia, half of the pups were fostered by normally treated nurse animals to control for possible maternal effects. (2) The animals were tested on postnatal days (PD) 36, 86, 120 and 150 by applying three different behavioural tests: prepulse inhibition (PPI), social interaction and recognition, and motor activity in an open field. (3) Before the PD 150 test, half of the animals had been chronically treated with the antipsychotic drug clozapine (45 mg/kg/day). RESULTS: Rats exposed to hypoxia as neonates exhibited a deficit in locomotor activity on PD 86, 120, and 150, as well as a PPI deficit on PD 120 and 150 but not before. Chronic treatment with clozapine reverses the hypoxia induced PPI deficit, but not the decreased locomotor activity. In a second experiment, clozapine was chronically administered before PD 120 and blocked the development of the PPI deficit in the animals exposed to hypoxia. DISCUSSION: The time course of the hypoxia-induced PPI deficit and reversibility by clozapine supports the validity of our animal model and the hypothesis that hypoxia as an obstetric complication is an important factor in the pathophysiology of schizophrenia.