Central Sensitization in the Bladder Pain Syndrome

Introduction: Nociceptive hyper-excitability and Central Sensitization (CS), have been identified as responsible for maintaining pain in several chronic neuropathic pain conditions, among which Bladder pain syndrome (BPS). Aim of the present study was to evaluate in patients with BPS the correlation between CS and the following items pain duration, the number of other CS related diseases, the number of tried treatments for pain and of diagnostic investigations before the proper diagnosis and to identify the cut-off value of the pain delays for predicting the worsening of sensitization. Method: Fifty-eight consecutively BPS outpatients were recruited from 2014 to 2016. They were submitted to Central Sensitization Inventory (CSI), Overactive Bladder Questionnaire (OAB-8v) and visual analogic scale (VAS) for pain. We used a descriptive analysis (mean, standard deviation, range) and Spearman and Kendall test coefficient as correlation index. One-way ANOVA test was used for the comparison between groups. P-value less than 0.05 were required for statistical significance. We used receiver operating characteristic (ROC) curve analysis to retrospectively analyze the association between the years of the disease and pathological values o of CSI. Results: The patients were observed after 13.1 + 11.0 years by the onset of The CSI score was 69.7+15.8. Resulting significantly lower in patients with BPS onset in the last year the correlation between CSI and the disease duration was significant. The number of previous investigations was 3.7 + 2.8while the number of previous treatments for chronic pain was 5.9 + 3.1, resulting significantly related to CSI score. The OAB-8v was 21 + 7.5 (range 2-34). The worsening of the symptoms related to the overactive bladder at OAB-8v was related to a greater CS. After 1,5 years of the onset of the pain the CS show a progressive worsening. The mean number of other diseases (fibromyalgia, irritable bowel syndrome, anxiety or depression, migraine, neck injury, Panic Disorder Attack, chronic fatigue syndrome, temporomandibular joint syndrome, restless leg syndrome, multiple chemical sensitivities) associated to CS was 2.8+1.9. The correlation between the number of diseases associated to CS and the years of disease resulted significant. Conclusion: Patients with long lasting pelvic pain show high levels of CS, and other central sensitivity syndromes (CSS) together to worsening of overactive bladder symptoms, and increasing number of used drugs. The delay of diagnosis is related to a greater sensitization process

Modulation of human corticospinal excitability by paired associative stimulation in patients with amyotrophic lateral sclerosis and effects of Riluzole

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that causes an impairment in both the upper and lower motor neurons. The recent description of numerous non-motor signs points to an involvement of the neocortex networks that is more complex than was previously believed. Paired associative stimulation (PAS), a combination of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation, can enhance motor output in the contralateral hand through an NMDA-mediated sensorimotor mechanism. OBJECTIVE To describe the effects of PAS on ALS patients before and after Riluzole intake compared with healthy subjects. METHODS PAS was used to detect differences between 24 newly-diagnosed ALS patients and 25 age-matched healthy controls. MEP amplitude from the abductor pollicis brevis was considered before PAS, immediately after (T0) and after 10 (T10), 20 (T20), 30 (T30) and 60 (T60) minutes. Statistical significance was calculated using RM-ANOVA. RESULTS In healthy controls, PAS significantly increased MEP amplitude at T10, T20 and T30 (p < 0.05). In ALS patients, a significant increase in MEP amplitude was also observed after 60 min (p < 0.05), thus demonstrating NMDA-mediated enhanced facilitatory plasticity. After two weeks of riluzole intake, no MEP amplitude increase was evident after PAS at any time point. In three monomelic-onset ALS patients, sensorimotor facilitation was evident only in the hemisphere corresponding to the affected side and appeared in the opposite hemisphere when the patients manifested contralateral symptoms. CONCLUSIONS PAS may be considered a useful tool when investigating NMDA-mediated neocortical networks in ALS patients and the modulation of such networks after anti-glutamatergic drug intake

The synergistic effect between positivity, socio-demographic factors and smoking cessation: results of a cohort study

OBJECTIVE: To examine the extent to which a effect does exist between Positivity (POS), smoking and socio-demographic factors in determining quitting smoking in subjects participating in a Group Counselling Program (GCP) for smoking cessation.METHODS: 481 subjects were contacted through a telephone call. A logistic regression analysis was carried out. Possible interaction between sociodemographic variables and POS level was tested using the Synergism Index (SI).RESULTS: For individuals with a POS level over or equal to 3.4 the odds of being smoker was significantly higher among females (OR = 1.55), who smoked at home (OR = 2.16) and lower if there had children at home (OR = 0.53). For individuals with a POS level under 3.4, the only significant variable associated with smoking was beinga female (OR = 2.58). As far concerns the synergistic effect between the variables considered does exist between POS levels and having children at home (SI=1.13) and female gender (SI = 2.8).CONCLUSIONS: The synergistic effect between POS and sociodemographic factors adds evidence on the use of POS as possible determinants of individual happiness

Reading a GEM with a VLSI pixel ASIC used as a direct charge collecting anode

In MicroPattern Gas Detectors (MPGD) when the pixel size is below 100 micron and the number of pixels is large (above 1000) it is virtually impossible to use the conventional PCB read-out approach to bring the signal charge from the individual pixel to the external electronics chain. For this reason a custom CMOS array of 2101 active pixels with 80 micron pitch, directly used as the charge collecting anode of a GEM amplifying structure, has been developed and built. Each charge collecting pad, hexagonally shaped, realized using the top metal layer of a deep submicron VLSI technology is individually connected to a full electronics chain (pre-amplifier, shaping-amplifier, sample and hold, multiplexer) which is built immediately below it by using the remaining five active layers. The GEM and the drift electrode window are assembled directly over the chip so the ASIC itself becomes the pixelized anode of a MicroPattern Gas Detector. With this approach, for the first time, gas detectors have reached the level of integration and resolution typical of solid state pixel detectors. Results from the first tests of this new read-out concept are presented. An Astronomical X-Ray Polarimetry application is also discussed.Comment: 11 pages, 14 figures, presented at the Xth Vienna Conference on Instrumentation (Vienna, February 16-21 2004). For a higher resolution paper contact [email protected]

Evaluation of Major Minerals and Trace Elements in Wild and Domesticated Edible Herbs Traditionally Used in the Mediterranean Area

The human diet is characterized by the intake of major minerals (Na, K, Ca, Mg, P, N) and trace elements (Zn, Mn, Se, Cu, Fe, Co, I, Cr, F, Pb, Cd) for their key role in many metabolic functions. Nowadays, the research of sources able to improve their intake is in continuous evolution, especially in the undeveloped countries. In this sense, wild edible herbs, commonly used since ancient times, can represent a good alternative to improve the daily human intake of minerals. In this study, four wild edible species, Rumex acetosa, Picris hieracioides, Cichorium intybus, and Plantago coronopus, were analyzed for their content in Na, K, Ca, Mg, Cu, Mn, Fe, and Zn and, besides, three domestications (named “soilless,” pot, and open field) were evaluated in the analyzed species in the prospective of their commercialization as valuable sources of minerals in the human diet. Nitrate and oxalate contents were also evaluated, given their negative impact on human health. Results unveil that open field domestication allowed the plants to maintain the content of major minerals similar to those measured in wild plants, especially in C. intybus and P. hieracioides. The trace elements Cu, Mn, Fe, and Zn were not recorded at high content irrespectively to the wild collection or domestications. Finally, plants grown in the open field also accounted for a high oxalate and nitrate content, especially in R. acetosa. Further researches should be aimed at decreasing the oxalate and nitrate content in the domesticated species and to promote the commercialization of the domesticated species

Antioxidant properties of plant polyphenols in the counteraction of alcohol-abuse induced damage: impact on the mediterranean diet

Polyphenols are antioxidants contained in plants as olive and grape. As part of the Mediterranean diet, they may decrease the risk of cancer, of chronic and neurodegenerative diseases. Alcohol consumption plays a detrimental effect on health, causing tissue damage and disrupting the metabolism of Neurotrophins (NTs). NTs are crucial proteins for the life cycle of neuronal and non-neuronal cells. Alcohol abuse elicits changes in NTs levels in the brain and in other target organs, however, it was observed minor damage in animals early exposed to red wine, probably due to the antioxidant effects of polyphenols. Indeed, data show that resveratrol or other polyphenols extracted from the olive can effectively counteract serum free radicals’ formation caused by chronic alcohol intake, contrasting also alcohol-induced NTs liver elevation. The aim of the present review is to update pieces of evidences about the antioxidant properties of polyphenols and their role in counteracting alcohol-induced damage

Comparison of three domestications and wild-harvested plants for nutraceutical properties and sensory profiles in five wild edible herbs: Is domestication possible?

In this study, five wild edible herbs traditionally consumed in the Tuscany region (Italy) were evaluated for their potential in human nutrition. The nutraceutical characterization of Rumex acetosa, Cichorium intybus, Picris hieracioides, Sanguisorba minor, and Plantago coronopus, as well as their sensory profile were reported. Additionally, a preliminary assessment of completely different domestication of the wild species (named "soilless", pot, and open field) was conducted to verify the possibility of their marketability, which is impossible if the plants are only gathered as wild. The open field domestication allowed to obtain plants with nutraceutical and sensory profiles similar to those of the wild species, especially in C. intybus, P. hieracioides, and S. minor. The pot domestication allow to obtain plants with chlorophyll and carotenoid contents close to those of the wild species, as well as a lower total phenolic and flavonoid content and ascorbic acid content than wild species. In the "soilless"method, R. acetosa and P. coronopus exhibited a high quality in terms of phytochemicals and antioxidant activity. Afterward, the sensory profile was strongly affected by the domestication in terms of the palatability, except for R. acetosa and P. coronopus, which displayed Hedonic Index (HI) values close to the consumer acceptability limit (HI = 6). A sensory profile similar to that of wild species was reported in open field domestication, whereas a worse sensory profile was reported in P. hieracioides and C. intybus domesticated using the soilless method. Finally, according to the preliminary assessment carried out in this study through an analysis of the general nutraceutical properties, S. minor was shown to be the most promising species thanks to its intrinsically highest nutraceutical properties considering the marketability of wild edible herbs as "new"functional food. However, further research on the bioavailability and bioactivity tests of nutraceutical compounds present in this species are required to confirm the findings of this study

Effect of drying methods on phenolic compounds and antioxidant activity of Urtica dioica L. leaves

Stinging nettle (Urtica dioica) is a plant well known in traditional medicine for its many beneficial properties, but the lack of standardization regarding the product to offer to consumers limits its diffusion. To this end, drying appears to be a useful technique to offer a low-cost product that can be stored for long time, but the different drying procedures may give rise to end-products of very different quality as nutraceutical and antioxidant compounds. Nettle leaves have been dehydrated employing freeze-drying (FD), oven-drying (OD) or heat pump drying (HPD) and compared with fresh leaves following water extraction to emulate the use by final consumers. Results indicate that the best dehydration technique is HPD, which apparently gives rise to more than a doubling of total phenols and antioxidant activity in the extract compared to the water extract obtained from fresh leaves but a reduction in the level of ascorbic acid of about 39%. In addition, the content of some phenolic compounds is 10 to over a hundred times higher in the extract after HPD than that obtained from fresh samples. This confirms that the dehydration technique should be tuned in relation to the compounds of greatest interest or value

Sexual developmental disorders in pediatrics

Disorders of sex development (DSD) are a heterogeneous group of pathologies that result in an alteration in sex determination or differentiation. DSD are estimated to affect 1: 4,500 newborns and according to the 2006 Chicago Consensus classification, DSD can be divided into three categories: those with a 46 XX karyotype, those with a 46 XY karyotype and those relating to sex chromosomes. It is crucial to correctly identify the pathology already in the first days of life to direct the patient and his family to the best path of care. For this reason, the role of the pediatrician is fundamental in the correct identification of the clinical picture and in supporting the family during the long process that involves the management of these patients. To make a diagnosis, it is necessary to follow a path led by a multidisciplinary team that includes several steps such as the execution of the genetic analysis, the evaluation with diagnostic imaging methods and laboratory evaluations. The therapeutic management, on the other hand, is still very complex even if in recent years we have moved from an attitude of early gender reassignment to an approach of watchful waiting to let the patient choose when she/he is mature enough to do so, which gender she/he feels to belong. It should not be forgotten that throughout this process the pediatrician must be both supportive and clinically active in the management of the child and his family

Glutamate-mediated blood-brain barrier opening. implications for neuroprotection and drug delivery

The blood-brain barrier is a highly selective anatomical and functional interface allowing a unique environment for neuro-glia networks. Blood-brain barrier dysfunction is common in most brain disorders and is associated with disease course and delayed complications. However, the mechanisms underlying blood-brain barrier opening are poorly understood. Here we demonstrate the role of the neurotransmitter glutamate in modulating early barrier permeability in vivo Using intravital microscopy, we show that recurrent seizures and the associated excessive glutamate release lead to increased vascular permeability in the rat cerebral cortex, through activation of NMDA receptors. NMDA receptor antagonists reduce barrier permeability in the peri-ischemic brain, whereas neuronal activation using high-intensity magnetic stimulation increases barrier permeability and facilitates drug delivery. Finally, we conducted a double-blind clinical trial in patients with malignant glial tumors, using contrast-enhanced magnetic resonance imaging to quantitatively assess blood-brain barrier permeability. We demonstrate the safety of stimulation that efficiently increased blood-brain barrier permeability in 10 of 15 patients with malignant glial tumors. We suggest a novel mechanism for the bidirectional modulation of brain vascular permeability toward increased drug delivery and prevention of delayed complications in brain disorders. SIGNIFICANCE STATEMENT: In this study, we reveal a new mechanism that governs blood-brain barrier (BBB) function in the rat cerebral cortex, and, by using the discovered mechanism, we demonstrate bidirectional control over brain endothelial permeability. Obviously, the clinical potential of manipulating BBB permeability for neuroprotection and drug delivery is immense, as we show in preclinical and proof-of-concept clinical studies. This study addresses an unmet need to induce transient BBB opening for drug delivery in patients with malignant brain tumors and effectively facilitate BBB closure in neurological disorders