Simple, compact, high-resolution monochromatic x-ray source for characterization of x-ray calorimeter arrays.

X-ray calorimeters routinely achieve very high spectral resolution, typically a few eV full width at half maximum (FWHM). Measurements of calorimeter line shapes are usually dominated by the natural linewidth of most laboratory calibration sources. This compounds the data acquisition time necessary to statistically sample the instrumental line broadening and can add systematic uncertainty if the intrinsic line shape of the source is not well known. To address these issues, we have built a simple, compact monochromatic x-ray source using channel cut crystals. A commercial x-ray tube illuminates a pair of channel cut crystals that are aligned in a dispersive configuration to select the Kα1 line of the x-ray tube anode material. The entire device, including the x-ray tube, can be easily hand-carried by one person and may be positioned manually or using a mechanical translation stage. The output monochromatic beam provides a collimated image of the anode spot with magnification of unity in the dispersion direction (typically 100 µm-200 µm for the x-ray tubes used here) and is unfocused in the cross-dispersion direction so that the source image in the detector plane appears as a line. We measured output count rates as high as 10 count/s/pixel for the Hitomi soft x-ray spectrometer, which had 819 µm square pixels. We implemented different monochromator designs for energies of 5.4 keV (one design) and 8.0 keV (two designs), which have effective theoretical FWHM energy resolution of 0.125 eV, 0.197 eV, and 0.086 eV, respectively; these are well-suited for optimal calibration measurements of state-of-the art x-ray calorimeters. We measured an upper limit for the energy resolution of our Cr Kα1 monochromator of 0.7 eV FWHM at 5.4 keV, consistent with the theoretical prediction of 0.125 eV.

Quantitative examination of isometric tongue protrusion forces in children with oro-facial dysfunctions or myofunctional disorders.

Oro-facial dysfunctions (OFD) or oro-facial myofunctional disorders in children lead to severe problems in teeth and jaw position, articulation, chewing and swallowing. The forces of the tongue, the central muscle for articulation, chewing and swallowing are focused on in several studies. In this examination, isometric tongue protrusion forces (TPF) of children with OFD and controls were compared. Thirty participants with OFD and 30 controls were presented a target force level as a straight line on a monitor that they were supposed to match by generating an isometric tongue force for different target levels (0.25 N and 0.5 N). Correlations of the severity of OFD (symptom score) with the capacities of the TPF 0.25 N and 0.5 N were calculated. Statistical differences were obvious in TPF variability and the accuracy, depending on the weight. Tongue contact time, expressed as per cent (TCT, total contact: 100%), was significantly lower in children with OFD (P = .005). Mean and median TPF was not different between groups. The predictive value of TPF for OFD revealed a level of 58.6% for TPF 0.25 N and 74.5% for TPF 0.5 N. Correlations of the severity of OFD were seen for some parameters. Subjects with OFD show significantly lower competencies in accuracy and endurance of tongue protrusion forces. This may have a high impact on phenotyping children with OFD and influence therapeutical approaches.

[Position paper of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery and the German Society of Phoniatrics and Pediatric Audiology - current state of clinical and endoscopic diagnostics, evaluation, and therapy of swallowing disorders in children and adults]. / Positionspapier der DGHNO und der DGPP - Stand der klinischen und endoskopischen Diagnostik, Evaluation und Therapie von Schluckstörungen bei Kindern und Erwachsenen.

Position Paper of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery and the German Society of Phoniatrics and Pediatric Audiology - Current State of Clinical and Endoscopic Diagnostics, Evaluation, and Therapy of Swallowing Disorders in Children and AdultsSwallowing disorders are frequent. The main concern is mortality due to aspiration induced pneumonia and malnutrition. On the other hand quality of life is severely affected. The demographic trend indicates an increase of dysphagia in the future. Neurodegenerative diseases, tumors of the digestive tract and sequelae of tumor treatment in the head and neck region are the main pathologic entities.Predominantly ENT physicians and phoniatrists, are asked for diagnostics and therapy who will coordinate the interdisciplinary treatment according to the endoscopic findings.A differentiated approach in history, diagnostics, and symptom oriented treatment is necessary for the mostly complex disorders. The integration of non-medical personnel such as logopeds (speech language pathologists), physiotherapists, and occupational therapists in planning and executing an effective therapy expands and completes the patient-oriented care. Conservative treatment by these therapists is an important pillar in the treatment. Parts of the specific diagnostics can be taken over by them in close cooperation.In particular an interdisciplinary cooperation with the staff from intensive care medicine is indispensable.The diagnostic procedures of specific endoscopy as described in this position paper are part of the primary and fundamental tasks of ENT specialists and phoniatrists.Endoscopy is a medical service that is basically not delegable. Consequently substitution of the physician is precluded.

Electrochemical control of a non-covalent binding between ferrocene and beta-cyclodextrin.

The forces required for the detachment of ferrocene (Fc) from ß-cyclodextrin (ßCD) in a single host (ßCD)-guest (Fc) complex were investigated using force spectroscopy under electrochemical conditions. The redox state of the guest Fc moiety as well as the structure of the supporting matrix was found to decisively affect the nanomechanical properties of the complex.

[Changes in dose and injection pattern in the botulinum toxin long-term therapy of facial dyskinesis]. / Änderung von Dosis und Injektionsmuster der Botulinumtoxin-Langzeittherapie fazialer Dyskinesien.

BACKGROUND: Rare information exists about comparative long-term observations of patients with facial movement disorders. This retrospective analysis deals with the course of different parameters of injection over the time. METHODS: In this study we compared the development of long-term botulinum toxin treatments of patients with blepharospasm, hemifacial spasm and synkinesis. 80 patients (n=30 blepharospasm, n=31 hemifacial spasm, n=19 synkinesis), who had at least 10 consultations for BTA-injections, were included in the retrospective analysis. The development for each entity in total dosage, increase in the number of injection points and change in dosages for each point were evaluated. RESULTS: The over-all dosage in all 3 clinical disorders and for each single disease itself increased continuously over the time. The amount of injection points increased in the treatment of hemifacial spasm and synkinesis. The dosage per point increased most in blepharospasm between the 1. and 25. injection, but was distinctly lower in patients with hemifacial spasm and synkinesis. The increase in dosage in blepharospasm is therefore, in contrast to the other indications, mostly caused by an increase in dosage per point. In patients with hemifacial spasm and synkinesis the escalation of dosage is mainly caused by an increase of the number of injection points. CONCLUSION: These new aspects of the dynamic in the treatment with botulinum toxin enable the physician to understand better the dynamic of these diseases, to optimize treatment protocols.

Effects of dietary polyunsaturated fatty acids on mitochondria.

Type and quantity of ingested dietary fat contribute to the onset and progression of chronic diseases such as diabetes, obesity or arteriosclerosis. Attention is increasingly focussing on effective therapies for these diseases as well as functional foods that impede the development of insulin resistance and obesity. Studies provided evidence showing polyunsaturated fatty acids of the omega-3 and the omega-6 families play beneficial roles in prevention and treatment of diseases as diverse as Alzheimer's disease, cancer and cardiovascular diseases such as myocardial infarction, arrhythmia, atherosclerosis and hypertension. Strongest evidence is derived from in vitro experiments on cultured cells and animal-based studies, while the results from clinical studies are inconclusive. After ingestion, polyunsaturated fatty acids are distributed to cells and enriched in cellular membranes, where they influence cellular metabolism and survival. Polyunsaturated fatty acids are involved in various mitochondrial processes including mitochondrial calcium homeostasis, gene expression, respiratory function, ROS production and mitochondrial apoptosis. Therefore, mitochondria play a central role in the mechanisms underlying the protective effects of polyunsaturated fatty acids. The complex mechanisms involved in the effects of polyunsaturated fatty acid on mitochondrial actions depend on structural properties, cellular uptake, shuttling and metabolism, competition with intracellular stores as well as inherent properties of fatty acid metabolites. This review will summarize recent findings on the effects of various types of polyunsaturated fatty acids on mitochondria.

Sodium/hydrogen exchange inhibition with cariporide reduces leukocyte adhesion via P-selectin suppression during inflammation.

BACKGROUND AND PURPOSE: The Na(+)/H(+) exchange (NHE) inhibitor cariporide is known to ameliorate ischaemia/reperfusion (I/R) injury by reduction of cytosolic Ca(2+) overload. Leukocyte activation and infiltration also mediates I/R injury but whether cariporide reduces I/R injury by affecting leukocyte activation is unknown. We studied the effect of cariporide on thrombin and I/R induced leukocyte activation and infiltration models and examined P-selectin expression as a potential mechanism for any identified effects. EXPERIMENTAL APPROACH: An in vivo rat mesenteric microcirculation microscopy model was used with stimulation by thrombin (0.5 micro ml(-1)) superfusion or ischaemia (by haemorrhagic shock for 60 min) and reperfusion (90 min). KEY RESULTS: Treatment with cariporide (10 mg kg(-1) i.v.) significantly reduced leukocyte rolling, adhesion and extravasation after thrombin exposure. Similarly, cariporide reduced leukocyte rolling (54+/-6.2 to 2.4+/-1.0 cells min(-1), P<0.01), adherence (6.3+/-1.9 to 1.2+/-0.4 cells 100 microm(-1), P<0.01) and extravasation (9.1+/-2.1 to 2.4+/-1.1 cells per 20 x 100 microm perivascular space, P<0.05), following haemorrhagic shock induced systemic ischaemia and reperfusion. The cell adhesion molecule P-selectin showed a profound decrease in endothelial expression following cariporide administration in both thrombin and I/R stimulated groups (35.4+/-3.2 vs 14.2+/-4.1% P-selectin positive cells per tissue section, P<0.01). CONCLUSIONS AND IMPLICATIONS: The NHE inhibitor cariporide is known to limit reperfusion injury by controlling Ca(2+) overload but these data are novel evidence for a vasculoprotective effect of NHE inhibition at all levels of leukocyte activation, an effect which is likely to be mediated at least in part by a reduction of P-selectin expression.

Increased cardiac endothelial nitric oxide synthase expression in patients taking angiotensin-converting enzyme inhibitor therapy.

BACKGROUND: The efficacy of angiotensin-converting enzyme (ACE) inhibitors has been demonstrated in large clinical trials, but knowledge of the underlying mechanisms remains incomplete. Therefore, this study investigated the impact of ACE inhibitor therapy on cardiac nitric oxide (NO) synthases in patients with coronary artery disease (CAD) or heart failure. PATIENTS AND METHODS: The mRNA expression was quantified by standard calibrated competitive RT-PCR, protein expression by Western blotting and NOS activity by monitoring the conversion of [3H]arginine to [3H]citrulline during enzymatic formation of NO in tissue homogenates of myocardium of patients with, or without, ACE inhibitor treatment before elective coronary artery bypass grafting or heart transplantation. RESULTS: The mRNA expression (amol microg(-1) RNA) of endothelial NO synthase (eNOS) was higher (22.5 +/- 4.8, n = 23) in the atrial myocardium of patients taking ACE inhibitor treatment, before elective coronary artery bypass grafting, compared with patients not taking this therapy (8.9 +/- 0.7, n = 33, P < 0.0001). The ACE inhibitor therapy increased eNOS protein expression from [(9 +/- 0.7) relative units (RUs) to (12 +/- 0.9) RUs, P < 0.05, respectively] and cardiac NOS activity from 17.6 +/- 1.3 to 23.7 +/- 1.1 pmol mg protein(-1) min(-1) (P < 0.001, respectively). Inducible and neuronal NO synthase expression was not changed by the ACE inhibition. A similar up-regulation of eNOS by ACE inhibition was found in the left ventricles of patients with heart failure. The augmented endothelial NOS expression and activity was not the result of differences in clinical characteristics and concomitant therapy between the patient groups. CONCLUSION: Increased eNOS expression and activity might contribute to the beneficial effects of ACE inhibitor therapy in the treatment of CAD and heart failure.

Ondansetron does not reduce the shivering threshold in healthy volunteers.

BACKGROUND: Ondansetron, a serotonin-3 receptor antagonist, reduces postoperative shivering. Drugs that reduce shivering usually impair central thermoregulatory control, and may thus be useful for preventing shivering during induction of therapeutic hypothermia. We determined, therefore, whether ondansetron reduces the major autonomic thermoregulatory response thresholds (triggering core temperatures) in humans. METHODS: Control (placebo) and ondansetron infusions at the target plasma concentration of 250 ng ml(-1) were studied in healthy volunteers on two different days. Each day, skin and core temperatures were increased to provoke sweating; then reduced to elicit peripheral vasoconstriction and shivering. We determined the core-temperature sweating, vasoconstriction and shivering thresholds after compensating for changes in mean-skin temperature. Data were analysed using t-tests and presented as means (sds); P<0.05 was taken as significant. RESULTS: Ondensetron plasma concentrations were 278 (57), 234 (55) and 243 (58) ng ml(-1) at the sweating, vasoconstriction and shivering thresholds, respectively; these corresponded to approximately 50 mg of ondansetron which is approximately 10 times the dose used for postoperative nausea and vomiting. Ondansetron did not change the sweating (control 37.4 (0.4) degrees C, ondansetron 37.6 (0.3) degrees C, P=0.16), vasoconstriction (37.0 (0.5) degrees C vs 37.1 (0.3) degrees C; P=0.70), or shivering threshold (36.3 (0.5) degrees C vs 36.3 (0.6) degrees C; P=0.76). No sedation was observed on either study day. CONCLUSIONS: /b>. Ondansetron appears to have little potential for facilitating induction of therapeutic hypothermia.

Surgical and conservative methods for restoring impaired motor function - facial nerve, spinal accessory nerve, hypoglossal nerve (not including vagal nerve or swallowing).

The present review gives a survey of rehabilitative measures for disorders of the motor function of the mimetic muscles (facial nerve), and muscles innervated by the spinal accessory and hypoglossal nerves. The dysfunction can present either as paralysis or hyperkinesis (hyperkinesia). Conservative and surgical treatment options aimed at restoring normal motor function and correcting the movement disorders are described. Static reanimation techniques are not dealt with. The final section describes the use of botulinum toxin in the therapy of dysphagia.

[Botulinum toxin in otorhinolaryngology]. / Praktische Anwendung von Botulinumtoxin im Kopf-Hals-Bereich.

BACKGROUND AND OBJECTIVES: Through its anticholinergic effect, botulinum toxin is a suitable therapeutic option for dysfunctions of the muscular and the autonomic nervous system. PATIENTS/METHODS: Beside the classical indications like facial hyperkinesis (i.e. blepharospasm, hemifacial spasm), the treatment of complex dystonias (oromandibular dystonia, spasmodic dystonia, cervical dystonia), gustatory sweating, hypersalivation and crocodile tears is successful. Botulinum toxin is an alternative treatment of tension type headache and migraine. A new indication of botulinum toxin application may involve the treatment of nasal hypersecretion through the effect on the nasal glands. RESULTS: The positive therapeutic effect starts a few days after treatment and lasts longer in disorders of the autonomic nervous system. Because of its temporally limited therapeutic effect, the patients need further treatment. Side-effects are rare. CONCLUSIONS: Botulinum toxin is an effective treatment for a variety disorders with different etiologies and has very few side effects.

[Botulinum toxin in ENT medicine]. / Botulinum-Toxin in der Hals-Nasen-Ohrenheilkunde.

In otorhinolaryngology, botulinum toxin is a suitable therapeutic option in the muscular and the autonomic nervous system concerning dysfunctions. Respecting some special aspects, it is an effective treatment for disorders of different etiology with very few side-effects. The positive therapeutic effect is temporarily limited, so that the patients need further treatment. Beside the classical indications like the facial hyperkinesias (i.e. blepharospasms, hemifacial spasm) the treatment of complex dystonias (oromandibular dystonia, laryngeal dystonia, cervical dystonia), gustatory sweating, hypersalivation and crocodile tears is successful. Botulinum toxin is an alternative treatment of tension type headache and migraine. A new indication of botulinum toxin application may lay in the treatment of nasal hypersecretion through the effect on the nasal glands.

Minimally invasive application of botulinum toxin type A in nasal hypersecretion.

We report on the effect of the local application of botulinum toxin A on nasal hypersecretion in a female patient with intrinsic rhinitis. 20 units of botulinum toxin A (Botox) was inserted into each nostril using a small sponge in close contact with the lower and middle turbinates. The effect was scored by the patient and by rhinomanometry. Nasal hypersecretion diminished clearly 5 days after the treatment. The rhinomanometric flow increased 2 weeks after the application. No side effects occurred. We conclude that this minimal invasive method of local botulinum toxin application might be a very effective and safe option for the treatment of nasal hypersecretion of different etiologies.

Botulinum toxin type A induces apoptosis in nasal glands of guinea pigs.

Nasal hypersecretion is predominantly caused by overaction of nasal glands, which are mainly under cholinergic control. In this work, we investigated the influence of botulinum toxin A (BTA) on the nasal mucosal tissue of the maxillary sinus turbinates of guinea pigs (n = 10) that were painlessly sacrificed 10 days (short-term group) or 3 months (long-term group) after local treatment with 20 units of BTA (Botox) or 0.2 mL of 0.9% sodium chloride (control). Histologic investigation of the nasal mucosal tissue of the BTA-treated animals (short-term group) showed degeneration of glands and ducts and apoptotic nuclei on TUNEL staining of these structures. The control animals revealed normal glandular tissue and no apoptosis. The animals of the long-term group showed almost normal glandular tissue and only a few apoptotic nuclei. In conclusion, BTA induces temporary apoptosis in the nasal glandular compartment of guinea pigs.

Treatment of gustatory sweating with botulinum toxin: special aspects.

Botulinum toxin treatment is an efficient, well-tolerated technique for patients suffering from gustatory sweating, first described by our group. With the experience gained in recent years we were able to improve on some of our skills in the diagnosis and treatment of gustatory sweating and here we wish to focus on some interesting aspects: (1) the necessity for an exact anamnesis before treatment with botulinum toxin to ensure correct treatment; (2) the advantages of Minor's test in special situations, for example, when sweating occurs in regions of hairy skin, retroauricular, at the back of the auricle and in areas distant from the site of salivary gland surgery; (3) the reduction of pain during treatment using an anesthetic ointment containing lidocaine and prilocaine as active substances; (4) intracutaneous injections in areas anterior to the fascia-protected skin of the lateral face-covering mimetic muscles, and (5) the occasional necessity for short-time reinjection in small areas of persistent sweating.

[Oromandibular dystonia. Clinical forms, diagnosis and examples of therapy with botulinum toxin]. / Oromandibuläre Dystonien - Klinische Formen, Diagnostik und Therapiebeispiele mit Botulinum Toxin -

BACKGROUND: The present study reports on our experience with clinical aspects and therapy of oromandibular dystonia (OMD) with botulinum toxin A. OMD is a very rare form of focal dystonias. The clinical symptoms can vary considerably, depending on the musculature affected. PATIENTS: The various clinical forms are described. The description of the diagnostic analysis and the therapy with botulinum toxin A is explained with reference to the patients. In these cases, injections are made into the musculature of the base of the mouth, the muscles involved in chewing, the extrinsic muscles of the tongue and the caudal facial musculature. RESULTS: Most of the patients showed an improvement of their symptoms. The average dose of Botox(R) used was 35.4+/-23.6 units. The duration of the effect was 14+/-9.2 weeks on average. CONCLUSION: The therapy for OMD using botulinum toxin A has proved to be successful, the amount of improvement in this form of dystonia is, however, lower in comparison to other forms of mobility disorders in the head and neck region.

Chronic N(G)-nitro-L-arginine methyl ester-induced hypertension : novel molecular adaptation to systolic load in absence of hypertrophy.

BACKGROUND: Chronic N(G)-nitro-L-arginine methyl ester (L-NAME), which inhibits nitric oxide synthesis, causes hypertension and would therefore be expected to induce robust cardiac hypertrophy. However, L-NAME has negative metabolic effects on protein synthesis that suppress the increase in left ventricular (LV) mass in response to sustained pressure overload. In the present study, we used L-NAME-induced hypertension to test the hypothesis that adaptation to pressure overload occurs even when hypertrophy is suppressed. METHODS AND RESULTS: Male rats received L-NAME (50 mg. kg(-1). d(-1)) or no drug for 6 weeks. Rats with L-NAME-induced hypertension had levels of systolic wall stress similar to those of rats with aortic stenosis (85+/-19 versus 92+/-16 kdyne/cm). Rats with aortic stenosis developed a nearly 2-fold increase in LV mass compared with controls. In contrast, in the L-NAME rats, no increase in LV mass (1. 00+/-0.03 versus 1.04+/-0.04 g) or hypertrophy of isolated myocytes occurred (3586+/-129 versus 3756+/-135 microm(2)) compared with controls. Nevertheless, chronic pressure overload was not accompanied by the development of heart failure. LV systolic performance was maintained by mechanisms of concentric remodeling (decrease of in vivo LV chamber dimension relative to wall thickness) and augmented myocardial calcium-dependent contractile reserve associated with preserved expression of alpha- and beta-myosin heavy chain isoforms and sarcoplasmic reticulum Ca(2+) ATPase (SERCA-2). CONCLUSIONS: When the expected compensatory hypertrophic response is suppressed during L-NAME-induced hypertension, severe chronic pressure overload is associated with a successful adaptation to maintain systolic performance; this adaptation depends on both LV remodeling and enhanced contractility in response to calcium.

Macrolide Analogues of the Novel Immunosuppressant Sanglifehrin: New Application of the Ring-Closing Metathesis Reaction.

Macrocycles containing a conjugated 1,3-diene moiety have been synthesized for the first time in good yields by the ring-closing metathesis reaction [Eq. (1)]. The new compounds represent cyclophilin-binding, simplified analogues of the macrocyclic core of sanglifehrin A, an immunosuppressant which binds with high affinity to cyclophilin.