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Endothelin-1 (ET-1) is one of the most potent vasoconstrictors known to date. While its plasma or serum concentrations are elevated in some forms of experimental and human hypertension, this is not a consistent finding in all forms of hypertension. Matrix metalloproteinases -2 and -9 (MMP-2 and MMP-9), which degrade collagen type IV of the vascular basement membrane, are responsible for vascular remodeling, inflammation, and atherosclerotic complications, including in type 2 diabetes (T2D). In our study, we compared concentrations of ET-1, MMP-2, and MMP-9 in pre-hypertensive (PHTN) and hypertensive (HTN) T2D patients with those of healthy normotensive controls (N). ET-1, MMP-2, and MMP-9 were measured by ELISA. Concentrations of ET-1 in PHTN and N were very similar, while those in HTN were significantly higher. Concentrations of MMP-2 and MMP-9 in PHTN and HTN were also significantly higher compared to N. An interesting result in our study is that concentrations of MMP-2 and MMP-9 in HTN were lower compared to PHTN. In conclusion, we showed that increased production of ET-1 in patients with T2D can lead to long-lasting increases in blood pressure (BP) and clinical manifestation of hypertension. We also demonstrated that increased levels of MMP-2 and MMP-9 in pre-hypertensive and hypertensive patients with T2D mainly reflect the early vascular changes in extracellular matrix (ECM) turnover.

Responses are faster when the task-irrelevant orientation of a graspable object's handle corresponds to the location of the response hand. Over the past decade, research has focused on dissociating between two competing accounts of this effect: One rooted in motoric object affordances and the other resting on attentional mechanisms (i.e., Simon effect). Following this avenue of inquiry, we conducted three experiments, in which subjects had to respond bimanually to grayscale photographs of frying pans and saucepans. In addition to horizontal orientation (control/leftward/rightward handles), Experiments 1 and 2 also manipulated the direction of exogenous attentional shifts (left/right) using laterally placed, colored markers within the objects. Both experiments yielded regular Simon effects based on the location of the colored markers. However, in stark contrast to previous research, a negative stimulus-response compatibility effect was obtained with regard to the orientation of the graspable handles. This reversed affordance effect was also observed using the original, unedited grayscale photographs (Experiment 3), which suggested that its occurrence cannot be attributed to the use of colored markers. These unexpected findings appear to support the idea that Simon effects result from automatic and exogenous attentional orienting mechanisms, whereas affordances arise from controlled and endogenous attentional processes. Such a top-down attentional account of affordance can accommodate the observed reversal of the effect in the context of task characteristics.

Germination of seeds of root parasites like broomrapes ( Orobanchaceae ) is tightly regulated by chemical products exuded from the roots of the host plant, known as germination stimulants (GSs). Changes in the levels of synthesis and emission of GS can allow the development of practical measures for control of the crops-harming parasitic species. However, the genes encoding enzymes responsible for GS biosynthesis are still unknown. We performed a large-scale screening of 62,000 Arabidopsis activation-tag mutants for alteration in susceptibility to Phelipanche ramosa and to identify lines with altered GS production among them. After five successive screenings we identified 36 lines with altered susceptibility to P. ramosa . Seven of them displayed altered levels of GS production. By using a combination of Southern blot and thermal asymmetric interlaced polymerase chain reaction (TAIL-PCR), we pinpointed the location of activation-tag constructs in these lines. A combination of differential display and quantitative real-time PCR (qRT-PCR) allowed us to identify several affected genes. Two of them are directly involved in isoprenoid biosynthetic pathway in chloroplasts, and we believe that their activation led to increased levels of GS production. We believe that these genes are responsible for increased GS production in five of the Arabidopsis lines resistant to P. ramosa .

It has been established that the task-irrelevant orientation of an object's graspable handle produces a stimulus-response compatibility effect, resulting in faster reaction times when the location of the response corresponds to that of the object's handle. There is ongoing debate whether to attribute this affordance effect to motoric or to attentional components. In an attempt to reconcile these two viewpoints, we employed a novel experimental approach for investigating the relationship between attention and affordance. Using 3-D positional sound, auditory spatial attention was manipulated in order to explore its effects on affordance. Subjects were presented images of everyday graspable objects and had to respond bimanually (left or right) whether the object (featuring a leftward or rightward handle) was presented upright or upside-down. Prior to each affording object, sound localization cues were manipulated so as to orient auditory attention to the left, or to the right of the interaural axis (control). We obtained a peculiar pattern of results, which not only appears to provide support for an attention-shift account of affordance but does so in a cross-modal context.

A mechanism for grain growth and formation in the interstellar medium is proposed. In this mechanism, hydrogen molecules act as moderators. The process begins when they physisorb to the surface of the grain. Then, when a collision with a heavy atom occurs, the bonding energy is carried away by the evaporation of hydrogen molecules. Estimates are made of the number of hydrogen molecules bound to the surface of a grain that would be sufficient to facilitate this mechanism at 13 K for amorphous carbon and 8 K for a silicate grain.

The long-term effects of vagus nerve stimulation (VNS) on seizure frequency were studied in 30 patients with Lennox-Gastaut syndrome. Median observation time was 52 months (17-123). The effect parameters investigated were total number of seizures and different seizure types. The median reduction in number of seizures was 60.6%. The effects of VNS varied considerably between seizure types. Best effects were observed with atonic seizures (80.8% median reduction, number of responders: 8/12), followed closely by tonic seizures (73.3% median reduction, number of responders: 8/13). Least effects were with generalized tonic-clonic seizures (median reduction 57.4%, number of responders: 11/20). Additional positive effects included milder or shorter ictal or postictal phase in 16 patients. Improved alertness was reported in 76.7%. Adverse effects, of which drooling and voice alteration were most frequent, were reported in 20 patients. There was a statistically significant reduction in the median number of antiepileptic drugs used. The discontinuation rate was 16.7%.

Unlabelled: Tuberculous spondylitis (TS) frequently poses both diagnostic and therapeutic challenges. The clinical symptoms, radiological imaging studies and laboratory tests are quite often inconclusive in the early stages of the disease., Goal: To identify early clinical symptoms, review results from radiological imaging studies and laboratory tests to establish their diagnostic value and determine the effect of conservative therapy in patients with early TS., Results: Twenty two (22) patients with TS subjected to conservative therapy were studied. Medullary compression syndrome was found in 10 patients. The highest diagnostic value was established by Magnetic Resonance Imaging (MRI) data for discitis engaging two adjacent vertebrae and QuantiFERON TB Gold and T SPOT.TB tests. The effect of the disease on 12 patients, whose treatment had started before the collapse of the bodies of the vertebrae was non-occurrence of any residual deformity of the spinal column. The effect on 9 patients, whose therapy started at a later stage was a recovery of the neurological deficiency and deformity occurrence of various degrees., Conclusion: Repetitive lateral plain radiographs, MRI and QuantiFERON TB Gold test have proven of highest diagnostic value at this stage of the disease in our patients. The presence of clinical data, accelerated ESR levels, plain radiography and MRI evidence of an inflammatory process preceding the occurrence of bone destruction and the formation of paravertebral soft tissue collection provide sufficient reasons to conduct QuantiFERON TB Gold or T SPOT.TB testing and start an antituberculous therapy. In the frequent cases when the diagnosis cannot be sufficiently proven, we recommend empirical anti-tuberculous therapy.

Introduction: Urinary bladder diverticula are frequently resulting from obstructions. Our literature review did not reveal any cases of acquired urinary bladder diverticulum caused by long-term transurethral catheterization., Case Presentation: We report a rare case of a nonobstructive big urinary bladder diverticulum developed after a long-term urethral catheterization in a 62-year old male diabetic patient with normal subvesical urinary tract. The diverticulum was demonstrated by ultrasonography. Its formation was associated with the decubital changes of the bladder wall when the Foley catheter stayed for a longer period., Conclusion: Ultrasonographic examination of the urinary bladder is necessary to exclude such complication after a long-lasting catheterization as well as to maximally restrict the catheter's stay in the urinary bladder.

Objectives: Short-course therapy has been advocated for the treatment of community-acquired pneumonia (CAP). We compared the efficacy and safety of 5 and 7 day courses of gemifloxacin for outpatient treatment of mild-moderate CAP., Patients and Methods: In a multicentre, double-blind, parallel group study, patients were randomized to receive 320 mg of oral gemifloxacin once daily for 5 or 7 days. Over 95% of all patients in each cohort had a Fine score of

Two coexisting adsorption states of molecularly adsorbed acetylene on the Si(001)-(2 x 1) surface have been identified by a combined study based on the high-resolution electron energy loss spectroscopy and density functional computations. Seven possible adsorbate-substrate structures are considered theoretically including their full vibrational analysis. Based on a significantly enhanced experimental resolution, the assignment of 15 C2H2- and C2D2-derived vibrational modes identifies a dominant di-sigma bonded molecule adsorbed on top of a single Si-Si dimer. Additionally there is clear evidence for a second minority species which is di-sigma bonded between two Si-Si dimers within the same dimer row (end-bridge geometry). The possible symmetries of the adsorbate complexes are discussed based on the specular and off-specular vibrational measurements. They suggest lower than ideal C(2v) and C(s) symmetries for on-top and end-bridge species, respectively. At low coverages the symmetry reductions might be lifted.

We investigated the circulating cytotoxic CD160+ CD8(high) subset in correlation to antiviral immunity and response to highly active antiretroviral therapy (HAART) in HIV+ subjects. The study included 45 treatment-naive patients receiving HAART for 18 months, retrospectively defined as good (n=29) and transient (n=16) responders. HIV-specific CD8 T lymphocyte levels were measured by IFNgamma production in response to p17 Gag, in the presence of immobilized anti-CD160 mAb. We report a significantly increased baseline level of CD160+ CD8(high) subset in good therapy responders. CD160+ CD8(high) subset correlates with CD4+ T cell count, immune activation, and viral load. CD160+ CD8(high) lymphocytes contain a high amount of Granzyme B and include virus-specific T lymphocytes in HIV-1+ subjects. Co-stimulation through CD160 molecules enhances IFNgamma production in response to p17 Gag. Therefore, the CD160+ CD8(high) subset may be useful for monitoring of virus-specific cellular immunity and predicting response to antiretroviral therapy in chronic HIV-1 infection.

Axotomy of peripheral nerve stimulates events in multiple cell types that initiate a limited inflammatory response to axonal degeneration and simultaneous outgrowth of neurites into the distal segments after injury. We found that pharmacological blockade of RAGE impaired peripheral nerve regeneration in mice subjected to RAGE blockade and acute crush of the sciatic nerve. As our studies revealed that RAGE was expressed in axons and in infiltrating mononuclear phagocytes upon injury, we tested the role of RAGE in these distinct cell types on nerve regeneration. Transgenic mice expressing signal transduction-deficient RAGE in mononuclear phagocytes or peripheral neurons were generated and subjected to unilateral crush injury to the sciatic nerve. Transgenic mice displayed decreased functional and morphological recovery compared with littermate controls, as assessed by motor and sensory conduction velocities; and myelinated fiber density. In double transgenic mice expressing signal transduction deficient RAGE in both mononuclear phagocytes and peripheral neurons, regeneration was even further impaired, suggesting the critical interplay between RAGE-modulated inflammation and neurite outgrowth in nerve repair. These findings suggest that RAGE signaling in inflammatory cells and peripheral neurons plays an important role in plasticity of the peripheral nervous system.

Axotomy of peripheral nerve triggers events that coordinate a limited inflammatory response to axonal degeneration and initiation of neurite outgrowth. Inflammatory and neurite outgrowth-promoting roles for the receptor for advanced glycation end products (RAGE) have been suggested, so we tested its role in peripheral nerve regeneration. Analysis of immunohistochemical localization of RAGE by confocal microscopy revealed that RAGE was expressed in axons and infiltrating mononuclear phagocytes upon unilateral sciatic nerve crush in mice. Administration of soluble RAGE, the extracellular ligand binding domain of RAGE, or blocking F(ab')2 fragments of antibodies raised to either RAGE or its ligands, S100/calgranulins or amphoterin, reduced functional recovery as assessed by motor and sensory nerve conduction velocities and sciatic functional index and reduced regeneration, as assessed by myelinated fiber density after acute crush of the sciatic nerve. In parallel, in mice subjected to RAGE blockade, decreased numbers of mononuclear phagocytes infiltrated the distal nerve segments after crush. These findings provide the first evidence of an innate function of the ligand/RAGE axis and suggest that RAGE plays an important role in regeneration of the peripheral nervous system.

A coarse-grained model for protein-folding dynamics is introduced based on a discretized representation of torsional modes. The model, based on the Ramachandran map of the local torsional potential surface and the class (hydrophobic/polar/neutral) of each residue, recognizes patterns of both torsional conformations and hydrophobic-polar contacts, with tolerance for imperfect patterns. It incorporates empirical rates for formation of secondary and tertiary structure. The method yields a topological representation of the evolving local torsional configuration of the folding protein, modulo the basins of the Ramachandran map. The folding process is modeled as a sequence of transitions from one contact pattern to another, as the torsional patterns evolve. We test the model by applying it to the folding process of bovine pancreatic trypsin inhibitor, obtaining a kinetic description of the transitions between the contact patterns visited by the protein along the dominant folding pathway. The kinetics and detailed balance make it possible to invert the result to obtain a coarse topographic description of the potential energy surface along the dominant folding pathway, in effect to go backward or forward between a topological representation of the chain conformation and a topographical description of the potential energy surface governing the folding process. As a result, the strong structure-seeking character of bovine pancreatic trypsin inhibitor and the principal features of its folding pathway are reproduced in a reasonably quantitative way.

A recent theory for the long time dynamics of flexible chain molecules is applied for the first time to a peptide of biological importance, the neurotransmitter met-enkephalin. The dynamics of met-enkephalin is considerably more complicated than that of the previously studied glycine oligomers; met-enkephalin contains the interesting motions of phenyl groups and of side chains relative to the backbone, motions that are present in general flexible peptides. The theory extends the generalized Rouse (GR) model used to study the dynamics of polymers by providing a systematic procedure for including the contributions from the memory function matrices neglected in the GR theory. The new method describes the dynamics by time correlation functions instead of individual trajectories. These correlation functions are analytically expressed in terms of a set of equilibrium averages and the eigenvalues and eigenfunctions of the diffusion operator. The predictions of the theory are compared with Brownian dynamics (BD) simulations, so that both theory and simulation use identical potential functions and solvent models. The theory thus contains no adjustable parameters. Inclusion of the memory function contributions profoundly affects the dynamics. The theory produces very good agreement with the BD simulations for the global motions of met-enkephalin. It also correctly predicts the long-time relaxation rate for local motions.

This method can be applied to the non-drug treatment of diseases. It provides an exact evaluation of the healing effect by keeping the acupuncture point from overload. This method is realized by a bistable/monostable square wave oscillator. The electrical pulses for the treatment of the acupuncture point are delivered from the noninverted oscillator output. Their electrical parameters: frequency, pulse duration, rise time and coefficient of filling depend on the constantly changeable biophysical parameters of the acupuncture point, such as complex skin impedance (z), and total infrared skin thermal emission (te). Pulses from the inverted oscillator output are provided to the acoustic and visual channels. In the acoustic channel, the pulses are controlled only by amplitude. The visual output channel pulses apply to the amplitude- frequency circuit, where an amplitude-frequency analysis is performed. The output pulses of three electrical filters (low, middle and high frequency), control three sources of light, respectively red, green, and blue. Three colors blend on the white screen, as the color picture is modulated by the two biophysical parameters of the acupuncture point. These parameters are in a constant dynamics. The audio channel output information is delivered to the audio-information gate of the patient, reaching the Central Nervous System (CNS). The video channel output information is applied to the video-information gate and then to the patient's CNS, preparing it for appropriate therapeutical programs.

A case of malignant quickly progressing Henoch-nephritis is described, with a lethal end one and a half month after the initial manifestations. The disease develops with a clinical picture typical for systemic vasculitis, with joint-pain, skin-rash and grave abdominal syndrome, being the reason for unnecessary surgical intervention. The renal changes originate even at the very beginning of the disease and are clinically characterized, besides the exceptionally quick evolution, by the picture of acute renal insufficiency with progressing azotemia, severe electrolyte disturbances and anemic syndrome and pathomorphologically by the picture of severe diffuse intra- and extracapillary proliferative glomerulitis. The treatment with antihistamine preparations, heparin and corticosteroids failed to give an effect.

The selectivity of different kinds of electrodes for recording of single motor unit potentials was theoretically evaluated. A new type of selective "branched", superficial and subcutaneous wire electrodes was described. The discharge of single alpha motoneurons during movements against elastic resistance was investigated studying motor unit potentials in m. biceps brachii and m.interosseus dorsalis l. Depending on the velocity of the movement, the following pattern of discharge was found: 1) At slow velocity the frequency of discharge increased and new motor units were recruited. 2) At higher velocity the frequency of discharge was constant. The muscle force increased only when new motor units were recruited. 3) At very quick ballistic movements the frequency of discharge decreased during the movement.