New high-performance liquid chromatography-dad method for analytical determination of arbutin and hydroquinone in rat plasma

Natural substances present in herbal preparations should be carefully used because they can give toxic or therapeutic effects despite of their amount or the way of administration. The safety of products of vegetable origin must be assessed before commercialisation by monitoring the active ingredients and their metabolites. This study was therefore designed to identify and quantify arbutin and its metabolite hydroquinone, naturally present in Arctostaphylos uva-ursi (L.) Spreng plant in rat plasma, after an acute and subacute administration of aqueous arbutin solution in Wistar rats. For this purpose a reversed-phase high-performance liquid chromatography coupled with photodiode array detection was developed to assess the pharmacokinetic of arbutin and hydroquinone in plasma of female rats treated with aqueous arbutin solutions. The detection (arbutin: 0.0617 µg/ml and hydroquinone 0.0120 µg/ml) and quantification (arbutin: 0.2060 µg/ml and hydroquinone: 0.0400 µg/ml) limits were determined. At the arbutin concentration level of 10.7 µg/ml repeatability was 13.33% and its recovery 93.4±6.93%, while at the hydroquinone concentration level of 10.6 µg/ml repeatability was 11.66% and its recovery 92.9±7.75%. Furthermore the method was fully validated and the obtained data indicate that the new method provides good performances

Network conduciveness with application to the graph-coloring and independent-set optimization transitions

We introduce the notion of a network's conduciveness, a probabilistically interpretable measure of how the network's structure allows it to be conducive to roaming agents, in certain conditions, from one portion of the network to another. We exemplify its use through an application to the two problems in combinatorial optimization that, given an undirected graph, ask that its so-called chromatic and independence numbers be found. Though NP-hard, when solved on sequences of expanding random graphs there appear marked transitions at which optimal solutions can be obtained substantially more easily than right before them. We demonstrate that these phenomena can be understood by resorting to the network that represents the solution space of the problems for each graph and examining its conduciveness between the non-optimal solutions and the optimal ones. At the said transitions, this network becomes strikingly more conducive in the direction of the optimal solutions than it was just before them, while at the same time becoming less conducive in the opposite direction. We believe that, besides becoming useful also in other areas in which network theory has a role to play, network conduciveness may become instrumental in helping clarify further issues related to NP-hardness that remain poorly understood

A viral chitinase enhances oral activity of TMOF

In this study we investigate the combined effect on Heliothis virescens (Lepidoptera, Noctuidae) larvae of Aedes aegypti-Trypsin Modulating Oostatic Factor (. Aea-TMOF), a peptide that inhibits trypsin synthesis by the gut, impairing insect digestive function, and Autographa californica nucleopolyhedrovirus Chitinase A (AcMNPV ChiA), an enzyme that is able to alter the permeability of the peritrophic membrane (PM). Aea-TMOF and AcMNPV ChiA were provided to the larvae by administering transgenic tobacco plants, co-expressing both molecules. Experimental larvae feeding on these plants, compared to those alimented on plants expressing only one of the two molecules considered, showed significantly stronger negative effects on growth rate, developmental time and mortality. The impact of AcMNPV ChiA on the PM of H. virescens larvae, measured as increased permeability to molecules, was evident after five days of feeding on transgenic plants expressing ChiA. This result was confirmed by in vitro treatment of PM with recombinant ChiA, extracted from the transgenic plants used for the feeding experiments. Collectively, these data indicate the occurrence of a positive interaction between the two transgenes concurrently expressed in the same plant. The hydrolytic activity of ChiA on the PM of tobacco budworm larvae enhances the permeation of TMOF molecules to the ectoperitrophic space, and its subsequent absorption. The permeation through the paracellular route of Aea-TMOF resulted in a spotted accumulation on the basolateral domain of enterocytes, which suggests the occurrence of a receptor on the gut side facing the haemocoel. The binding of the peptide, permeating at increased rates due to the ChiA activity, is considered responsible for the enhanced insecticide activity of the transgenic plants expressing both molecules. These data corroborate the idea that ChiA can be effectively used as gut permeation enhancer in oral delivery strategies of bioinsecticides targeting haemocoelic receptors

Prevalence and direct costs of patients with neuromyelitis optica: data from Campania region in southern Italy

The study aimed to estimate the prevalence and direct costs of neuromyelitis optica (NMO) patients in Campania, Italy. Materials & methods: We retrospectively evaluated 53 NMO patients (mean age: 50.9 ± 16.5 years; 34% men) from the Campania Region administrative databases identified through disease exemption codes in 2018 and analyzed the incidence of NMO among the Campania region population and the disease-related cost. Results: The prevalence of NMO was 0.91 per 100,000 individuals. The average regional cost per NMO patient was 10,836.2 euros. The highest cost was related to drugs (60.6%), followed by hospitalizations (32.7%), diagnostics (4.8%) and laboratory tests (1.0%). Conclusion: NMO is an extremely rare disease with an annual disease-related cost of 0.005% of public health expenditur

G-CSF Prevents the Progression of Structural Disintegration of White Matter Tracts in Amyotrophic Lateral Sclerosis: A Pilot Trial

Background: The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). The current pilot study was performed to determine whether treatment with G-CSF in ALS patients is feasible.Methods: Ten patients with definite ALS were entered into a double-blind, placebo-controlled, randomized trial. Patients received either 10 mu g/kg BW G-CSF or placebo subcutaneously for the first 10 days and from day 20 to 25 of the study. Clinical outcome was assessed by changes in the ALS functional rating scale (ALSFRS), a comprehensive neuropsychological test battery, and by examining hand activities of daily living over the course of the study (100 days). The total number of adverse events (AE) and treatment-related AEs, discontinuation due to treatment-related AEs, laboratory parameters including leukocyte, erythrocyte, and platelet count, as well as vital signs were examined as safety endpoints. Furthermore, we explored potential effects of G-CSF on structural cerebral abnormalities on the basis of voxel-wise statistics of Diffusion Tensor Imaging (DTI), brain volumetry, and voxel-based morphometry.Results: Treatment was well-tolerated. No significant differences were found between groups in clinical tests and brain volumetry from baseline to day 100. However, DTI analysis revealed significant reductions of fractional anisotropy (FA) encompassing diffuse areas of the brain when patients were compared to controls. On longitudinal analysis, the placebo group showed significant greater and more widespread decline in FA than the ALS patients treated with G-CSF.Conclusions: Subcutaneous G-CSF treatment in ALS patients appears as feasible approach. Although exploratory analysis of clinical data showed no significant effect, DTI measurements suggest that the widespread and progressive microstructural neural damage in ALS can be modulated by G-CSF treatment. These findings may carry significant implications for further clinical trials on ALS using growth factors

Image cytometric analysis of p53 and mdm-2 expression in primary and recurrent mucoepidermoid carcinoma of parotid gland: immunohistochemical study

<p>Abstract</p> <p>Aims and Objectives</p> <p>This study aims to analyze immunocytochemically p53 aberrant expression and mdm-2 expression in primary and recurrent mucoepidermoid carcinoma (MEC) of parotid gland and to ascertain if expression of these markers correlates with tumor behavior, clinical outcome, histological grade and local recurrence.</p> <p>Methods</p> <p>20 cases histologically diagnosed as primary MEC with different grades were included in the study. Out of 20 cases, 7 were classified as grade I, 8 as grade II and 5 as grade III. Immunohistochemical staining of these 20 primary cases as well as 6 recurrent cases with anti-p53 and anti-mdm-2 antibodies was carried out. Area fraction of immunopositivity was estimated by image analysis software.</p> <p>Results</p> <p>16/20 primary cases were p53 +ve (80%). The p53 positive cases included 3 cases classified as grade (I), 8 cases as grade (II) and 5 cases as grade (III). All 6 recurrent cases were p53 +ve. On the other hand, 14/20 primary and only 2/6 recurrent cases were mdm-2 +ve. The mdm-2 +ve primary cases included 2 classified as grade (I), 7 as grade (II) and 5 as grade (III). 12 primary MEC showed co-expression of both p53 and mdm-2 of which 2 cases showed local recurrence.</p> <p>Conclusions</p> <p>these data suggested that expression of p53 and mdm-2 in primary and recurrent MEC correlates with the high histological grade. P53 aberrant expression is not only considered as an early event in MEC carcinogenesis but also correlates to tumor behavior and local recurrence. Mdm-2 overexpression is correlated to pathogenesis of MEC. However, no strong evidence was found between mdm-2 expression and MEC local recurrence.</p

Clinical history , interictal EEG and home-made video diagnostic accuracy: comparison with the VEPSG

Poiché la diagnosi differenziale degli episodi parossistici notturni è affidata alla VEPSG, tenendo conto dei limiti di tale metodica, il progetto attuale ha lo scopo di definire la resa diagnostica di strumenti alternativi alla VEPSG: anamnesi, home-made video ed EEG intercritico. Sono stati reclutati consecutivamente 13 pazienti, afferiti al nostro Dipartimento per episodi parossistici notturni. Ciascun paziente è stato sottoposto ad un protocollo diagnostico standardizzato. A 5 Medici Esperti in Epilessia e Medicina del Sonno è stato chiesto di formulare un orientamento diagnostico sulla base di anamnesi, EEG intercritico, home-made video e VEPSG. Attraverso l’elaborazione degli orientamenti diagnostici è stata calcolata la resa diagnostica delle procedure esaminate, a confronto con la VEPSG, attraverso il concetto di “accuratezza diagnostica”. Per 6 pazienti è stato possibile porre una diagnosi di Epilessia Frontale Notturna, per 2 di parasonnia, in 5 la diagnosi è rimasta dubbia. L’accuratezza diagnostica di ciascuna procedura è risultata moderata, con lievi differenze tra le diverse procedure (61.5% anamnesi; 66% home-made video; 69,2 % EEG intercritico). E’ essenziale migliorare ulteriormente l’accuratezza diagnostica di anamnesi, EEG intercritico ed home-made video, che possono risultare cruciali nei casi in cui la diagnosi non è certa o quando la VEPSG non è disponibile.Nocturnal frontal lobe epilepsy (NFLE) seizures appear almost exclusively during sleep. The differential diagnosis between this condition and sleep-related non-epileptic paroxysmal motor phenomena, in particular parasomnias, is arduous. Moreover, accepted criteria for the diagnosis of NFLE are lacking. At present video-polysomnographic recording of the seizures during sleep is the gold standard for the diagnosis but this technique is expensive and not available everywhere. The aim of this study is to measure the diagnostic accuracy of clinical history, interictal EEG and home-made video in distinguishing NFLE from non-epileptic paroxysmal sleep disorders. 13 patients who presented paroxysmal motor phenomena during sleep were consecutively enrolled in our Department and a specific diagnostic examination battery was performed. After the completion of the examinations the results were analyzed by five experts in clinical sleep medicine and epilepsy and a diagnostic decision was made: 6 subjects were classified as NFLE, 2 as parasomnias and 5 as “uncertain” diagnosis. From experts diagnostic decision, the clinical history, interictal EEG and home-made video diagnostic accuracy were calculated. The diagnostic accuracy was overall moderate and showed only slight differences between the procedures. However, it is essential to improve the diagnostic accuracy of clinical history, interictal EEG and home-made video recording that could be helpful in cases difficult to diagnose or when VEPSG monitoring is not available. In addition, future research should define reliable clinical and VEPSG criteria for the diagnosis of nocturnal frontal lobe seizures

A polycystic variant of a primary intracranial leptomeningeal astrocytoma: case report and literature review

<p>Abstract</p> <p>Background</p> <p>Primary leptomeningeal astrocytomas are rare intracranial tumors. These tumors are believed to originate from cellular nests which migrate by means of aberration, ultimately settling in the leptomeningeal structure. They may occur in both solitary and diffuse forms. The literature reports only fifteen cases of solitary primary intracranial leptomeningeal astrocytomas.</p> <p>Case presentation</p> <p>The authors report the case of a seventy-eight year-old woman with a polycystic variant of a solitary primary intracranial leptomeningeal astrocytoma. The first neurological signs were seizures and aphasia. CT and MRI scans demonstrated a fronto-parietal polycystic tumor adherent to the sub arachnoid space. A left fronto-temporo-parietal craniotomy revealed a tight coalescence between the tumor and the arachnoid layer which appeared to wrap the mass entirely. Removal of the deeper solid part of the tumor resulted difficult due to the presence of both a high vascularity and a tight adherence between the tumor and the ventricular wall.</p> <p>Conclusion</p> <p>A new case of a solitary primitive intracranial leptomeningeal astrocytoma of a rare polycystic variant is reported. Clinical, surgical, pathologic and therapeutic aspects of this tumor are discussed.</p

European position paper on the management of patients with patent foramen ovale. General approach and left circulation thromboembolism

The presence of a patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions; however, the subject remains controversial and no official statements have been published. This interdisciplinary paper, prepared with involvement of eight European scientific societies, aims to review the available trial evidence and to define the principles needed to guide decision making in patients with PFO. In order to guarantee a strict process, position statements were developed with the use of a modified grading of recommendations assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements of particular management options were weighed and graded according to predefined scales. Despite being based often on limited and non-randomised data, while waiting for more conclusive evidence, it was possible to conclude on a number of position statements regarding a rational general approach to PFO management and to specific considerations regarding left circulation thromboembolism. For some therapeutic aspects, it was possible to express stricter position statements based on randomised trials. This position paper provides the first largely shared, interdisciplinary approach for a rational PFO management based on the best available evidence