Social isolation-induced epigenetic changes in midbrain of adult mice.

Social isolation and loneliness increase the risk of death as much as well-established risk factors for mortality such as cigarette smoking and alcohol consumption. The underlying molecular mechanisms are poorly understood. In the present study, 3 months old male C57BL/6 mice were socially isolated by individual housing for another 3 months. At the age of 6 months, epigenetic changes were analyzed in midbrain. Social isolation of male adult mice led to an increased global DNA methylation, which was associated with enhanced activity of DNA methyltransferase. Di- and trimethylation of global histone H3 lysine 4 (H3K4) were increased in midbrain of socially isolated mice, accompanied by enhanced H3K4 histone methyltransferase activity. In addition, social isolation of adult mice led to activation of histone acetyltransferases as well as of histone deacetylases (HDAC) resulting in a net enhancement of histone H3 lysine 9 (H3K9) acetylation. Gene-specific effects were observed for Hdac1, Hdac3 and the serotonin transporter Slc6a4. Social isolation led to an up-regulation of Hdac1 and Hdac3, associated with decreased DNA methylation in the CpG island of the respective genes. On the contrary, the Slc6a4 gene was down-regulated, which was associated with enhanced DNA methylation. Collectively, the results from the present study demonstrate for the first time that social isolation of adult mice leads to a wide range of global epigenetic changes and these effects may have profound impact on gene expression pattern and phenotype of the socially isolated animals.

Green function of the double-fractional Fokker-Planck equation: path integral and stochastic differential equations.

The statistics of rare events, the so-called black-swan events, is governed by non-Gaussian distributions with heavy power-like tails. We calculate the Green functions of the associated Fokker-Planck equations and solve the related stochastic differential equations. We also discuss the subject in the framework of path integration.

[False aneurysm of the deep femoral artery due to pertrochanteric fracture of the hip with displaced fragment of the lesser trochanter]. / Aneurysma spurium der A. profunda femoris - Komplikation nach pertrochantärer Femurfraktur mit Dislokation des Trochanter minor.

We report the case of an 82-year-old man with a pertrochanteric fracture of the hip and an avulsion of the lesser trochanter. During the third postoperative week after unproblematic correction with a gamma nail, a swelling of the proximal thigh occurred. Angiographs showed a false aneurysm of the deep femoral artery which was treated by suture.

[Conservative treatment of lumbar spinal stenosis--a review]. / Konservative Behandlung der lumbalen Spinalkanalstenose--eine Ubersicht.

AIM: The aim of this study is to provide an analysis of the literature and our own experience in the conservative treatment of lumbar spinal stenosis. Although lumbar spinal stenosis is treated mostly non-operatively there are only a few reports in the literature about the results of conservative treatment. All the recent articles about surgical procedures for LSS mention ineffective preoperative treatment without explaining it. So far there have been no randomised clinical trials to obtain evidence regarding the clinical outcome of non-surgical management. METHOD: We provide an actual overview about the conservative treatment of LSS referring only to retrospective studies, guidelines and expert opinions. Solely the treatment of LSS with epidural steroids, which is recommended by most of the authors, has been evaluated by several randomised controlled studies with a high level of evidence. RESULTS: As far as we can summarise at present, a multidisciplinary conservative treatment programme is most effective not only for discogenic low-back pain but also for LSS with a concentration on physiotherapy, behavioural therapy, epidural injections and a special back training which is presented in this paper. CONCLUSION: Patients with LSS should receive a trial of the proposed conservative, aggressive treatment before surgery is considered.

Nitric oxide-mediated inhibition of androgen receptor activity: possible implications for prostate cancer progression.

Chronic inflammation increases the risk of cancer and many cancers, including prostate cancer, arise at sites of chronic inflammation. Inducible nitric oxide synthase (iNOS) is an enzyme dominantly expressed during inflammatory reactions. Although synthesis of high amounts of nitric oxide (NO) by iNOS has been demonstrated in pathophysiological processes, such as acute or chronic inflammation, autoimmune diseases or tumorigenesis, the role of iNOS activity in most of these diseases is poorly understood. Analysing prostate cancer biopsies by immunohistochemistry we found iNOS protein expression in tumor cells strongly paralleled by nitrotyrosine suggesting that iNOS is fully active. In vitro, NO inhibits androgen receptor-dependent promoter activity and prostate specific antigen production as well as DNA-binding activity of the androgen receptor (AR) in a concentration-dependent manner. Inhibition of the activity of androgen receptor-dependent reporter constructs is neither owing to diminished AR protein levels nor owing to an inhibition of its nuclear import. In addition, NO inhibits the proliferation of androgen receptor-positive prostate cancer cells significantly more efficiently than proliferation of androgen receptor-negative prostate cancer cells. In summary, our findings suggest that intratumoral iNOS activity favors development of prostate cancer cells that are able to proliferate androgen receptor-independently, thereby promoting prostate tumor progression.

[Limited, haemoglobin-dependent indication for autologous blood donation in total hip or knee replacement]. / Eingeschränkte, Hämoglobin-abhängige Indikation zum Eigenblutverfahren bei Endoprothesenimplantation des Hüft- oder Kniegelenkes.

AIM: The rejection rate of autologous blood donation before joint replacement is high. The influence of the haemoglobin value and the age of patient before autologous blood donation was examined according to the necessity for blood transfusion. METHOD: In a retrospective study, the data of 233 patients who had donated autologous blood before hip (THR) or knee arthroplasty (TKR) were analysed. RESULTS: 72 patients (30.9 %) received an autologous blood transfusion during surgery or in the further course until the first day after surgery. A multivariate analysis showed no significant influence of age on the need for transfusions (p = 0.093), but a higher haemoglobin value before blood donation reduced the risk significantly to 0.712 per unit (1 g/dl). Therefore the age of the patient was less predictive compared to the haemoglobin value as to whether or not a blood transfusion had been necessary. CONCLUSION: The high security of homologous blood reached in the last years and the knowledge that autologous blood donation reduces the haemoglobin value before surgery has led to the procedure in our hospital only to perform autologous blood donation at the explicit request of the patient.

[Acute cardiovascular reactions to cervical nerve root infiltration]. / Akute Herz-Kreislaufreaktionen bei zervikaler Spinalnervenanalgesie.

AIM: The frequency of cardiovascular adverse effects of cervical nerve root infiltration was investigated by means of a prospective study. METHOD: The hemodynamic and respiratory parameters systolic and diastolic blood pressure, heart rate, respiratory rate and oxygen saturation were monitored continuously in 56 patients undergoing cervical spine nerve root infiltration (injection of 10 ml Lidocain 0.5 %, mean depth of injection 5 cm). The monitored time frame ranged from 5 minutes before to 10 minutes after its administration, an additional holter-monitoring began 1 day prior to the injection. RESULTS: Severe complications such as syncopes were not observed in any of the 56 patients, 4 patients developed presyncopes. None of the registered parameters showed a significant change. In a group of patients with known, pre-existing cardiovascular morbidity, no significant changes occurred either. No relevant cardiac arrhythmias were observed. CONCLUSION: The observed cardiovascular complications were not severe. Most probably, the observed reactions were vasavagal presyncopes. Supine positioning led to immediate recovery in all of these patients. A complete hemodynamic monitoring and the placement of an intravenous line do not seem to be absolute necessities in the routine cervical nerve root infiltration.

The RNA binding protein TIAR is involved in the regulation of human iNOS expression.

Human inducible NO synthase (iNOS) expression is regulated by post-transcriptional mechanisms. The 3'-untranslated region (3'-UTR) of the human iNOS mRNA contains AU-rich elements (ARE), which are known to be important for the regulation of mRNA stability. The 3'-UTR of the human iNOS mRNA has been shown to regulate human iNOS mRNA expression post-transcriptionally. One RNA-binding protein known to interact with AREs and to regulate mRNA stability is the T cell intracellular antigen-1-related protein (TIAR). In RNA binding studies TIAR displayed high affinity binding to the human iNOS 3'-UTR sequence. In RNase protection experiments, the cytokine incubation needed for iNOS expression did not change TIAR expression in DLD-1 cells. However, overexpression of TIAR in human DLD-1 colon carcinoma cells resulted in enhanced cytokine-induced iNOS expression. In conclusion, TIAR seems to be involved in the post-transcriptional regulation of human iNOS expression.

[Artificial discs: review, current status, outlook]. / Bandscheibenprothesen: Rückblick, Augenblick, Ausblick.

AIM: This paper gives an overview of the current status of artificial discs for the lumbar spine. METHODS: Recent publications and overviews in the literature with pro and contra opinions and the latest procedure of FDA approval are presented and discussed. Despite arguments to the contrary, an FDA panel is in favour of the premarket approval application for the Charité artificial disc because of good late follow-up results. Other lumbar artificial discs will follow. RESULTS: Follow-up studies only exist for the Charité and Prodisc endoprotheses. The results are comparable to those of lumbar fusion. However, randomized controlled studies are still missing. CONCLUSION: Proponents for lumbar artificial discs stand against the criticism of an unpredictable treatment for a condition that cannot be diagnosed with any precision. The current model should be a controlled indication with second opinions followed by professional surgery in spine centers.

End-to-end distribution function of stiff polymers for all persistence lengths.

We set up recursion relations for calculating all even moments of the end-to-end distance of Porod-Kratky wormlike chains in D dimensions. From these moments we derive a simple analytic expression for the end-to-end distribution in three dimensions valid for all peristence lengths. It is in excellent agreement with Monte Carlo data for stiff chains and approaches the Gaussian random-walk distributions for low stiffness.

Self-similar variational perturbation theory for critical exponents.

We extend field theoretic variational perturbation theory by self-similar approximation theory, which greatly accelerates convergence. This is illustrated by recalculating the critical exponents of O (N) -symmetric phi(4) theory. From only three-loop perturbation expansions in 4-epsilon dimensions, we obtain analytic results for the exponents, which are close to those derived recently from ordinary field-theoretic variational perturbational theory to seventh order. In particular, the specific-heat exponent is found to be in good agreement with best-measured exponent alpha approximately -0.0127 of the specific-heat peak in superfluid helium, found in a satellite experiment. In addition, our analytic expressions reproduce also the exactly known large- N behavior of the exponents.

Reentrant phenomenon in the quantum phase transitions of a gas of bosons trapped in an optical lattice.

We calculate the location of the quantum phase transitions of a Bose gas trapped in an optical lattice as a function of effective scattering length a(eff) and temperature T. Knowledge of recent high-loop results on the shift of the critical temperature at weak couplings is used to locate a nose in the phase diagram above the free Bose-Einstein critical temperature T((0))(c), thus predicting the existence of a reentrant transition above T((0))(c), where a condensate should form when increasing a(eff). At zero temperature, the transition to the normal phase produces the experimentally observed Mott insulator.

Gauge-invariant critical exponents for the Ginzburg-Landau model.

The critical behavior of the Ginzburg-Landau model is described in a manifestly gauge-invariant manner. The gauge-invariant correlation-function exponent is computed to first order in the 4-d and 1/n expansion, and found to agree with the ordinary exponent obtained in the covariant gauge, with the parameter alpha=1-d in the gauge-fixing term ( partial differential (mu)A(mu))(2)/2alpha.

Ultraviolet A1 radiation induces nitric oxide synthase-2 expression in human skin endothelial cells in the absence of proinflammatory cytokines.

Skin exposure to ultraviolet radiation from sunlight causes erythema and edema formation as well as inflammatory responses. As some of these ultraviolet-induced effects are potentially mediated by nitric oxide synthases, we examined the role of cytokines and ultraviolet A1 radiation (340-400 nm) on the expression of the nitric oxide synthase-2 in endothelia of normal human skin biopsies during short-term organ culture as well as expression and activity of the nitric oxide synthase-2 in in vitro cell cultures of human dermal endothelial cells. Both, cytokine challenge (interleukin-1beta + tumor necrosis factor-alpha + interferon-gamma) but also ultraviolet A1 exposure (50 J per cm2) in the absence of cytokines led to the expression of nitric oxide synthase-2 in human skin organ cultures as shown by immunohistochemistry. Moreover, exposing human dermal endothelial cell cultures to proinflammatory cytokines but also to ultraviolet A1 radiation (6-24 J per cm2) in the absence of cytokines resulted in significant nitric oxide synthase-2 mRNA and protein expression as well as enzyme activity. Ultraviolet A1 irradiation of cytokine activated cells led to further increases in nitric oxide synthase-2 mRNA, protein expression, and enzyme activity. Moreover, a reporter gene assay using a human nitric oxide synthase-2 promoter construct provide evidence that ultraviolet A1, in the absence of cytokines, induces nitric oxide synthase-2 expression and activity, as previously shown for cytokines. Thus, the results presented here demonstrate for the first time that in dermal endothelia of human skin ultraviolet A1 radiation alone represents a proinflammatory stimulus sufficient to initiate nitric oxide synthase-2 expression as well as activity comparable with the respective response seen in the presence of proinflammatory cytokines.

Fluctuation pressure of a stack of membranes.

We calculate the universal constants in Helfrich's pressure law for a stack of N membranes between walls by strong-coupling theory. Using the close analogy between this system and a stack of strings, where the universal constants are exactly known, we construct a smooth potential that keeps the membranes apart. The strong-coupling limit of the perturbative treatment of the free energy yields pressure constants for an arbitrary number of membranes, which are in very good agreement with values from Monte Carlo simulations.

Three-loop critical exponents, amplitude functions, and amplitude ratios from variational perturbation theory.

We use variational perturbation theory to calculate various universal amplitude ratios above and below Tc in minimally subtracted straight phi4 theory with N components in three dimensions. In order to best exhibit the method as a powerful alternative to Borel resummation techniques, we consider only two- and three-loops expressions where our results are analytic expressions. For the critical exponents, we also extend existing analytic expressions for two loops to three loops.

Recursive graphical construction of feynman diagrams and their multiplicities in straight phi(4) and straight phi2A theory

The free energy of a field theory can be considered as a functional of the free correlation function. As such it obeys a nonlinear functional differential equation that can be turned into a recursion relation. This is solved order by order in the coupling constant to find all connected vacuum diagrams with their proper multiplicities. The procedure is applied to a multicomponent scalar field theory with a straight phi(4) self-interaction and then to a theory of two scalar fields straight phi and A with an interaction straight phi2A. All Feynman diagrams with external lines are obtained from functional derivatives of the connected vacuum diagrams with respect to the free correlation function. Finally, the recursive graphical construction is automatized by computer algebra with the help of a unique matrix notation for the Feynman diagrams.

Criterion for dominance of directional over size fluctuations in destroying order

For systems that exhibit a second-order phase transition with a spontaneously broken continuous O(N) symmetry at low temperatures, we give a criterion for judging at which temperature T(K) long-range directional fluctuations of the order field destroy the order when approaching the critical temperature from below. The temperature T(K) lies always significantly below the famous Ginzburg temperature T(G) at which size fluctuations of finite range become important.

Amphotericin B severely affects expression and activity of the endothelial constitutive nitric oxide synthase involving altered mRNA stability.

The therapeutic use of the antifungal drug amphotericin B (AmB) is limited due to severe side effects like glomerular vasoconstriction and risk of renal failure during AmB administration. As nitric oxide (NO) has substantial functions in renal autoregulation, we have determined the effects of AmB on endothelial constitutive NO synthase (ecNOS) expression and activity in human and rat endothelial cell cultures. AmB used at concentrations of 0.6 to 1.25 microg ml(-1) led to increases in ecNOS mRNA and protein expression as well as NO production. This was the result of an increased ecNOS mRNA half-life. In contrast, incubation of cells with higher albeit subtoxic concentrations of AmB (2.5 - 5.0 microg ml(-1)) resulted in a decrease or respectively in completely abolished ecNOS mRNA and protein expression with a strongly reduced or inhibited ecNOS activity, due to a decrease of ecNOS mRNA half-life. None of the AmB concentrations affected promoter activity as found with a reporter gene construct stably transfected into ECV304 cells. Thus, our experiments show a concentration-dependent biphasic effect of AmB on expression and activity of ecNOS, an effect best explained by AmB influencing ecNOS mRNA stability. In view of the known renal accumulation of this drug the results reported here could help to elucidate its renal toxicity.