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Background and Purpose: Pure autonomic failure (PAF) presents primarily as cardiovascular autonomic failure and may phenoconvert to other neurodegenerative disorders. However, the involvement of other autonomic functions has been poorly evaluated. This study aims to characterize genitourinary and bowel dysfunction and explore their relationship with cardiovascular autonomic dysfunction. Methods: Pure autonomic failure patients underwent cardiovascular autonomic testing and an assessment of pelvic autonomic dysfunction using urinary, sexual symptoms questionnaires and a bladder diary. Demographic, clinical features and related medical comorbidities were assessed. Results: Twenty‐five patients (10 males) with PAF were included (mean age 71 ± 8 years; disease duration 13 ± 8 years). 96% (24/25) reported lower urinary tract symptoms, of which overactive bladder symptoms were most commonly reported (n = 23; 92%; median overactive subscore 8, interquartile range [IQR] 3–11), followed by voiding difficulties (n = 19; 76%; median low stream subscore 2, IQR 1–3) using the Urinary Symptom Profile; however, only four (16%) required clean intermittent self‐catheterization. Sexual dysfunction was common (n = 21; 84%) using the Arizona Sexual Experience Scale. Mild faecal incontinence and constipation were reported. 86% (19/22) had nocturnal polyuria (NP) and the median NP index was 47% (IQR 38%–51%; normal range <33%). 77% (10/13) had voiding dysfunction and 31% (4/13) had post‐void residual urine >100 mL. There were no significant correlations between the need for catheterization and the degree of NP with age, disease duration and cardiovascular autonomic parameters (p > 0.05). Conclusions: Nocturnal polyuria, genitourinary and bowel symptoms are commonly seen in PAF. The pathophysiology of NP in PAF is most likely multifactorial and may occur independent of cardiovascular autonomic failure. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Aim of the present study was to examine the adrenocortical activity in basal condition and following a mild stress exposure in long-term HRT-treated menopausal women. Menopausal women, long term users of HRT (14 subjects) were compared both to menopausal women who had never used HRT (14 subjects) and young pre-menopausal women (14 subjects). Study design: Morning and evening salivary cortisol secretion was measured in samples collected twice a day (08:00 in the morning and 08:00 in the evening). Mild stress response was evoked by administration of the Stroop color-word test (CWT). Salivary cortisol was measured immediately before the start, 15, 30 and 45min after the completion of the test. Results: Menopause appears not to be associated with an impairment of cortisol circadian fluctuation. Long-term use of HRT in menopause attenuated HPA activity either in basal condition or in response to mild stress exposure. With regard to the CWT performance, all menopausal women took significantly longer than young women to perform the test. However, long-term HRT significantly reduced the number of errors made during the test. Conclusions: The present study suggested that long-term HRT could help menopausal patients to cope with mild stress and to improve mental performances. [Copyright &y& Elsevier]

The effects of hydroxypropyl-β-cyclodextrin (HP-β-CD) and sulfobutylether-β-CD (SBE7-β-CD) on in vitro human skin penetration and retention of the sunscreen agent butyl-methoxydibenzoylmethane (BM-DBM) were investigated. The interaction between the UV filter and the cyclodextrins was studied in water by phase-solubility analysis. Solid complexes were prepared by the co-evaporation method and characterized by 1H NMR spectroscopy, thermal analysis and powder X-ray diffraction. Solutions containing BM-DBM free or complexed with cyclodextrins were applied to excised human skin in Franz diffusion cells and the amount of sunscreen permeated after 6 h into the stratum corneum, viable epidermis, dermis and receptor fluid was assessed by HPLC. As much as 14.10–16.78% of the applied dose of BM-DBM penetrated within the skin tissue. No sunscreen was detected in the dermis and in the receiver phase. The greater proportion (84.6–95.5%) of the absorbed UV filter was localized in the stratum corneum with no significant differences between uncomplexed or complexed BM-DBM. Notable levels (2.29% of the applied dose) of the sunscreen agent accumulated in the epidermis from the preparation containing free BM-DBM. The epidermal concentration of the UV filter was markedly reduced (0.66% of the applied dose) by complexation with SBE7-β-CD, whereas HP-β-CD had no effect. The decreased BM-DBM retention in the epidermal region achieved by SBE7-β-CD limits direct contact of the sunscreen and of its reactive photolytic products with the skin viable tissues. [Copyright &y& Elsevier]

The aim of this study was to investigate the influence of nanoparticle-based systems on the light-induced decomposition of the sunscreen agent, trans-2-ethylhexyl-p-methoxycinnamate (trans-EHMC). Ethylcellulose (EC) and poly-d,l-lactide-co-glycolide (PLGA) were used as biocompatible polymers for the preparation of the particulate systems. The “salting out” method was used for nanoparticle preparation and several variables were evaluated in order to optimize product characteristics. The photodegradation of the sunscreen agent in emulsion vehicles was reduced by encapsulation into the PLGA nanoparticles (the extent of degradation was 35.3% for the sunscreen-loaded nanoparticles compared to 52.3% for free trans-EHMC) whereas the EC nanoparticle system had no significant effect. Therefore, PLGA nanoparticles loaded with trans-EHMC improve the photostability of the sunscreen agent. [Copyright &y& Elsevier]

At the end of February 1991, a "triple-axis" high-resolution diffractometer for on powder sample measurements with synchrotron radiation was put in operation on the Adone wiggler line BX 1 at Frascati. The diffractometer is based on a Seifert goniometer, designed according to our specifications. During the project, particular attention was paid in assuring the highest reliability together with great flexibility in the use. In fact, the diffractometer can also be used in a "medium resolution" configuration. For preliminary alignment and data collection, it is possible to operate with a traditional x-ray tube, too. The alignment procedure of the diffractometer to the x-ray beam is very easy. Powder samples can be measured both on the flat holder and on the capillary. An IBM PC computer is used for the instrument actuation and preliminary on-line data collection, while a large software package has been developed for the data analysis performed by a Macintosh IIcx. The instrument performance has been tested with a standard Si sample and quartz and Ni oxide samples. For the two possible resolution configurations, a test on a NiO sample gave FWHM values of 0.16° and 0.04°, respectively, for the [012] peak. [ABSTRACT FROM AUTHOR]

The article presents an abstract of the study "Polyglutamine Tract Elongation in Spinal and Bulbar Muscular Atrophy: Is There a Correlation Between Intracellular Aggregate Formation and Motoneuronal Death?" The study will be presented at a joint meeting of the International Society for Neurochemistry and the European Society for Neurochemistry which will be organized in Berlin, Germany, from August 8-14, 1999. The study found no correlation between intracellular aggregate formation and motoneuronal death.

Hypothalamus-pituitaryadrenal (HPA) axis activity was monitored in 20 women with chronic migraine (CM), previously affected by medication overuse headache (MOH), in comparison to healthy women (20 subjects) by measuring salivary cortisol, testosterone, dehydroepiandrosterone-sulphate (DHEA-S) levels, and their ratios, one week after the end of the MOH rehabilitation procedure. The participants were instructed how to collect saliva samples at home, a procedure that was performed twice a day (08:00 a.m. and 8:00 p.m.). Morning and evening levels of cortisol were significantly increased in CM patients with respect to controls. With regard to the cortisol/DHEA-S ratio, an inverse marker of psycho-physical wellbeing, CM women showed significantly higher values than controls. Moreover, testosterone/cortisol ratios (anabolic/catabolic index of physical performance) were significantly lower in CM patients than in controls. In the present study, CM appears not to be associated with an impairment of cortisol and DHEAS circadian fluctuation; however, CM patients present alterations in HPA axis function that might contribute to metabolic and psychological alterations that have also been associated with CM. [ABSTRACT FROM AUTHOR]

Background Chronic idiopathic urticaria is a common skin disorder characterized by recurrent, transitory, itchy weals for more than 6 weeks. An autoimmune origin has been suggested based on the findings of auto-antibodies (Abs) directed against either the α subunit of the high-affinity IgE receptor or the IgE molecule in nearly half of the patients. Objective To identify other autoantigen targets in patients with chronic idiopathic urticaria. Methods We used pooled IgG derived from 133 patients with chronic idiopathic urticaria to screen a random peptide library to identify disease-relevant autoantigen peptides. Among the identified peptides, one was recognized by the vast majority of patients' sera. Abs against this peptide were affinity purified from the patients' sera and assayed for their ability to induce histamine release from basophils. Results We identified a peptide that showed similarity with the low-affinity IgE receptor (FcℇRII/CD23) expressed on lymphomonocytes and eosinophils. Anti-peptide IgG Abs purified from the patients' sera bound cell surface CD23 and were able to induce histamine release from basophils. This effect appeared to be mediated by the release of major basic protein from eosinophils upon engagement of CD23. The same effects were obtained with the sera from mice immunized with the CD23 peptide. Conclusion Our results indicate that patients with chronic idiopathic urticaria have Abs against CD23 and that eosinophils, which infiltrate the skin of these patients, play a crucial role in maintaining the disease through the release of major basic protein upon engagement of the low-affinity IgE receptor by such auto-Abs. [ABSTRACT FROM AUTHOR]

Human intravenous immunoglobulins (hIVIgs) are used in two broad categories of diseases: immunodeficiency and autoimmunity. Among the immune-mediated diseases hIVIgs are of benefit in idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and dermatomyositis. Chronic idiopathic pericarditis (CIP) is a chronic disease of unknown origin characterized by recurrent episodes of pericardial inflammation. The cause of the recurrence is unknown, although in some cases it may be traced to a viral infection and to the presence of antimyocardial antibodies. Since a viral infection can induce an autoimmune process through a mechanism of molecular mimicry, and since the optimal therapy for prevention of the recurrences has not been established, we reasoned that treatment with hIVIgs could be beneficial in our patients unresponsive to previous immunosuppressive therapies. We describe four patients affected by CIP treated with monthly high-dose hIVIgs (0.4 g/kg daily for 5 consecutive days) for five times followed by administration every 2 months. Three of the four patients could permanently discontinue steroid therapy and are still in remission after years of follow-up. Our experience suggests that hIVIgs therapy may be a useful and safe treatment for CIP in steroid-dependent patients. [ABSTRACT FROM AUTHOR]

Abstract Spinal cord motoneurones express high levels of androgen receptor. However, in responsive tissue, the effects of testosterone is often mediated by the more potent androgenic derivative 5-alpha-dihydrotestosterone (DHT). This compound is formed in androgen target cells by the enzyme 5-alpha-reductase. Two isoforms of the 5-alpha-reductase, with limited degree of homology, have been cloned, type 1 and type 2. The low affinity-constitutive type 1 isoenzyme is widely distributed in the body; the high affinity-androgen regulated 5-alpha-reductase type 2 is confined to androgen-dependent structures and shows a peculiar pH optimum at acidic values. We have previously shown that high levels of 5-alpha-reductase activity are detectable in rat spinal cord. Here, using reverse transcriptase-polymerase chain reaction, we show that both isoforms are expressed in the whole spinal cord of the rat. The enzymatic pH optimum measured in immortalized spinal cord motoneurones (NSC34) is typical of the type 2 isoenzyme. Using in situ hybridization technique, we found that 5-alpha-reductase type 2 is confined to the motoneuronal cells of the anterior horns of the rat spinal cord, the cells that also are known to express high levels of androgen receptor. Because of the close association of androgen receptor and 5-alpha alpha-reductase type 2, motoneuronal cells should be considered as target cells for androgens. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether homocysteine (Hcy) plasma levels are correlated with molecules indicative of endothelial cell and fibroblast activation, including endothelin‐1 (ET‐1) and monocyte chemoattractant protein‐1 and ‐3 (MCP‐1, MCP‐3), in patients with systemic sclerosis (SSc). Methods: Eighty‐two patients were enrolled in this study; the control group included 75 age‐ and sex‐matched subjects. Plasma Hcy was determined by high‐performance liquid chromatography; folic acid, and vitamin B 12 plasma levels were determined by a chemiluminescence method. ET‐1, MCP‐1, and MCP‐3 were determined by enzyme‐linked immunosorbent assay (ELISA). Analysis of the 677C→T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene was performed by polymerase chain reaction (PCR) and digestion with the enzyme Hinf I. Results: Hcy levels were lower in patients whereas ET‐1 was significantly higher in patients and correlated with MCP‐1. Stratification of the patients on the basis of Hcy levels was not associated with any statistical difference in the concentration of ET‐1, MCP‐1, and MCP‐3. Patients with diffuse disease presented the highest levels of ET‐1 and MCP‐1. The distribution of the MTHFR genotypes was not different in patients and controls. Conclusions: In SSc, Hcy plasma concentration does not influence ET‐1, MCP‐1, or MCP‐3 levels. On the contrary, ET‐1, a marker of vascular activation, correlates with MCP‐1, a chemokine involved in the fibrotic process of SSc. [ABSTRACT FROM AUTHOR]

Abstract Gonadal steroids are potent modulators of gonadotropin releasing hormone (GnRH) secretion, and androgen binding sites and 5α-reductase activity have been found in the immortalized GnRH secreting cell line GT1-1, suggesting the existence of a direct androgenic control of GnRH dynamics. Two isoforms of the 5α-reductase have been cloned with very different biochemical/functional properties: 5α-reductase type 1 (widely distributed in the body) and 5α-reductase type 2 (confined in androgen target structures). We have analysed whether, in GT1-1, androgen binding sites are linked to ‘classical’ androgen receptor, and which 5α-reductase isoform is active. Reverse transcriptase-polymerase chain reaction analysis showed that the mRNAs coding for androgen receptor and for the two 5α-reductase isoforms are all expressed in GT1-1 cells. However, the 5α-reductase enzymatic reaction showed a peak of activity at a narrow pH around 5.5, the optimum for the 5α-reductase type 2. The affinity for testosterone, of the enzyme present in GT1-1 cells, was very similar to that observed for the recombinant type 2 isozyme expressed in yeasts. The data indicate that GT1-1 cells (i) express a ‘classical’ androgen receptor and (ii) contain the 5α-reductase type 2 isoform, a specific marker of androgen-responsiveness. [ABSTRACT FROM AUTHOR]

A soft x-ray beamline, utilizing the radiation produced by the six-pole wiggler of the Adone storage ring, has been realized. The beamline allows the exposure of large area resists by means of a double-mirror scanning system or mechanically moving the wafer. The mechanical, geometrical, and spectral characteristics of the beamline will be described. [ABSTRACT FROM AUTHOR]

No abstract available Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Schnitzler's syndrome is a rare clinical condition characterized by chronic urticaria, intermittent fever, bone pain, arthralgia or arthritis, and monoclonal immunoglobulin M (IgM) gammopathy. Here we describe the case of a 48‐year‐old Italian female with a long history of arthralgia, leucocytosis, spiking fever, and chronic urticaria with severe pruritus. The IgM‐κ monoclonal component in the serum and bone densification on conventional X‐ray with hyperfixation on bone technetium scanning at the distal part of the femurs and at the proximal part of the tibias were detected 4 years after the onset of the symptoms. After many ineffective treatments, the use of pulse cyclophosphamide (CPX) resulted in complete remission of the disease that is still lasting after a 2‐year follow‐up. [ABSTRACT FROM AUTHOR]

Introduction Corticospinal excitability is transiently suppressed during motor preparation (Greenhouse et al., 2015 ) and when cancelling a prepared movement (Hoshiyama et al., 1997 ). Because MEPs are suppressed even in task-irrelevant muscles (Greenhouse et al., 2015; Hoshiyama et al., 1997 ), it has been proposed that there is a “global” inhibitory signal (Greenhouse et al., 2015) . Objectives We tested the whether the inhibition is global or specific to different excitatory interneuron circuits in primary motor cortex (M1). Materials & methods A controllable pulse parameter TMS (cTMS; Rogue Resolutions Ltd.) device was used to activate distinct interneuron circuits in M1 by changing the coil orientation (posterior–anterior, PA; anterior–posterior, AP) and TMS pulse width (30–120 μ s). Motor evoked potentials (MEPs) were elicited in the first dorsal interosseous muscle(s) using short AP- (AP 30 ) and long PA-directed (PA 120 ) pulses at various stages during: (1) a left/right choice reaction time task (CRTT) in which a non-informative warning cue appeared 0.5 s prior to the imperative signal indicated the required response; and (2) a Go/No-Go task in which a non-informative warning cue appeared 2 s prior to a Go or No-Go signal indicating to respond or not respond. Because TMS pulse specificity is greatest at low stimulus intensities, experiments were conducted with weak voluntary contraction (5–10% maximum) to reduce stimulus threshold. Results AP 30 pulses evoked MEPs with a longer latency than PA 120 pulses, confirming that different excitatory interneurons were recruited by the different pulse. [RH1] In the CRTT, the amplitude of AP 30 -evoked MEPs was suppressed at the time of the imperative stimulus in both responding and non-responding hands, whereas responses to PA 120 stimuli were unaffected (Fig. 1A) .[RH2] In the Go/No-Go task, AP 30 and PA 120 MEPs were suppressed to a similar extent in the No-Go condition near to the expected onset of movement (Fig. 1B). Conclusion During motor preparation for the CRTT there was a selective suppression of one interneuron circuit in M1. In contrast, a global inhibition of corticospinal excitability was observed following a decision not to move. The implication is that the mechanisms underlying each form of inhibition are at least partially distinct. [ABSTRACT FROM AUTHOR]

Introduction: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, characterized by demyelination and axonal degeneration. By means of Transcranial magnetic stimulation (TMS) MS has been studied. Disabilities correlate with alterations of TMS parameters such as prolonged central motor conduction time, prolonged motor evoked potentials (MEP) latencies and increased motor threshold (MT). TMS has also been used to explore movement-related cortical plasticity. In healthy subjects if exercise is non-exhausting, an early transient facilitation of MEPs can occur immediately after exercise (post-exercise facilitation) and also after 15min of rest (delayed facilitation). Neural mechanisms underlying post-exercise facilitation seem to reside within motor cortex. The delayed facilitation may be functional evidence of intracortical synaptic reorganization consequent to repetitive motor tasks. Objective: We aimed to compare cortical excitability in patients at early stage of MS versus healthy controls. Material and methods: In each subject TMS of non-dominant hemisphere was used to define MEP amplitude and motor threshold (MT). Then subjects performed 3 blocks (30-s, 60-s, and 90-s duration) of a bimanual motor task (exercise condition). Amplitude of MEPs elicited immediately after each block, and then after a 15-min rest period were compared with baseline to evaluate the presence of post-exercise facilitation and delayed facilitation. Patients were not receiving any immunomodulatory or immunosuppressive therapy and their Expanded Disability Status Scale score was between 1 and 2.5 Results: MT resulted significantly lower in patients compared to controls. Compared with baseline, controls had larger MEP amplitudes after 30 and SMP 60s of exercise (post-exercise facilitation) and also after the rest period (delayed facilitation). In contrast, MEP amplitudes in patients were not significantly different from baseline after any of the exercise conditions or following the rest period. Conclusion: Patients do not show the normal fluctuations of cortical excitability usually found after a bimanual finger motor task. These results suggest a modification in the central circuits and suppose a reduction or alteration in the cortical plasticity. The absence of postexercise facilitation and delayed facilitation in patients suggests a reduction or an alteration in neural plasticity that mediates functions such as learning and memory. We speculate that in SM patients capability to recover from functional impairments caused by demyelination is compromised. In patients at early stage of MS cortical excitability changes can occur before motor performances appear significantly altered. So, when patients present clinical symptoms and the disease becomes evident, cerebral mechanisms of compensation are already totally exploited, and possibility of further increasing performances are already lost. Like in chronic fatigue patients, and maybe in the majority of patients affected by central fatigue, impaired motor cortex plasticity may affect recovery of function in the motor system. [Copyright &y& Elsevier]

Introduction: Lateralization of manual dexterity is a striking example of interemispheric asymmetry in cortical organization. Transcranial magnetic stimulation (TMS) studies have documented handedness related functional asymmetries in corticomotor excitability. Particularly, TMS has been used to analyze movement related cortical plasticity. Motor evoked potentials (MEP) amplitude increases immediately after brief periods of exercise (post-exercise facilitation) and then increases again after a rest period of 15min following a defined motor task (delayed facilitation). The post-exercise facilitation seems to be due to transient increase of motor cortex excitability. Objective: The delayed facilitation seems to reflect an intra-cortical synaptic reorganization consequent to motor tasks. In the present study, we compared changes in cortical excitability from respectively dominant (DH) and non dominant hemisphere (NDH) in both right-handed and left-handed subjects in function of a bimanual non-fatiguing motor task. We evaluated handedness related asymmetries. Material and methods: As primary screening, the 24 enrolled subjects were classified as right or left handed by according to their description of the hand used for writing. Then, each subject completed the Edinburgh Handedness Inventory and was reclassified as a function of the handedness score. For each subject, the experimental protocol was repeated twice so that the cortical excitability could be separately assessed in each hemisphere. By mean of TMS, MEP amplitude, motor threshold, and silent period were assessed. Then subjects performed a bimanual motor task (regular repetitive opening-closing bilateral movements of the index finger onto the thumb). MEPs of the first dorsal interosseus were recorded before exercise (baseline condition), immediately after each exercise periods of 30, 60, 90s (exercise conditions), and after 15min of rest (rest condition). MEP amplitude elicited in each exercise conditions, and then in rest condition was compared with baseline, to evaluate the presence of post-exercise facilitation and delayed facilitation. Hemispheric differences of MEP amplitude after the rest period were related to the handedness score. Results: Mean threshold intensity of TMS was significantly lower for DH compared to NDH. MEP amplitude was significantly increased in exercise conditions, independently of the hemisphere stimulated. However, in rest condition, only the NDH presented increased MEP amplitude, showing delayed-facilitation. Handedness scores and MEP asymmetry in rest condition were positively correlated. Conclusion: Delayed facilitation asymmetry was lateralized to NDH and varied as a linear function of handedness. These results suggest that cortical plasticity changes in the two hemispheres. Our data provide evidence that DH and NDH answer differently to motor requests and they differently recover after exercise. Bimanual motor task induces changes in cortical excitability differently in the two hemispheres, in favor of the non-dominant site. We speculate that NDH has a “dormant potential” that can be activated if necessary. The examination of the effects of a bimanual motor task on cortical excitability may be relevant to better understanding cortical plasticity processes and may provide new tools to study neurological disorders characterized by central fatigue and less capacity to recovery. [Copyright &y& Elsevier]