Supported ionic liquids used as chromatographic matrices in bioseparation: an overview

Liquid chromatography plays a central role in biomanufacturing, and, apart from its use as a preparative purification strategy, either in biopharmaceuticals or in fine chemicals industries, it is also very useful as an analytical tool for monitoring, assessing, and characterizing diverse samples. The present review gives an overview of the progress of the chromatographic supports that have been used in the purification of high-value products (e.g., small molecules, organic compounds, proteins, and nucleic acids). Despite the diversity of currently available chromatographic matrices, the interest in innovative biomolecules emphasizes the need for novel, robust, and more efficient supports and ligands with improved selectivity. Accordingly, ionic liquids (ILs) have been investigated as novel ligands in chromatographic matrices. Given herein is an extensive review regarding the different immobilization strategies of ILs in several types of supports, namely in silica, Sepharose, and polymers. In addition to depicting their synthesis, the main application examples of these supports are also presented. The multiple interactions promoted by ILs are critically discussed concerning the improved selectivity towards target molecules. Overall, the versatility of supported ILs is here considered a critical point to their exploitation as alternatives to the more conventional liquid chromatographic matrices used in bioseparation processes.publishe

Multimodal ionic liquid-based chromatographic supports for an effective RNA purification

Nucleic acids have been considered interesting molecules to be used as biopharmaceuticals for the treatment of various diseases, in gene therapy strategies. In particular, RNA arises as the most promising approach because it does not require access to the nucleus of cells to exert its function; however, it is quite challenging due to its labile nature. To increase the possibility of translating RNA-based technology to clinical protocols, the biomanufacturing of RNAs has been intensively exploited in the last few years. However, the standard RNA purif ication processes remain time-consuming and present limitations regarding recovery yield and purity. This work describes the functionalization of chromatographic silica-based supports with four ionic liquids (ILs) composed of functional moieties that can promote distinct interactions with nucleic acids. After an initial screening to evaluate the binding and elution behavior of nucleic acids in the IL-based supports, SSi[C 3 C 3NH2 Im]Cl has shown to be the most promising for further purification assays. This support was studied for the RNA purification from different samples (clarified or more complex) and has shown to be highly effective, for all the conditions studied. Generally, it is here presented a new method for RNA isolation in a single step, using an IL-based chromatographic support, able to eliminate the usage of hazardous compounds often included in standard RNA extraction protocols.publishe

Pros and Cons of the SeHCAT Test in Bile Acid Diarrhea: A More Appropriate Use of an Old Nuclear Medicine Technique

Bile acid malabsorption (BAM) causing chronic diarrhea may be due to organic as well as functional disorders, and some of them were included under the general label of diarrheic-type irritable bowel syndrome (IBS-D). The 75-selenium homocholic acid taurine (SeHCAT) test is a nuclear medicine investigation considered to be the gold standard for the diagnosis of bile acid malabsorption (BAM). Many studies demonstrate that it could be effective in the clinical workout of chronic diarrhea due to different conditions. The SeHCAT test provides a quantitative assessment to estimate the severity of BAM and the possible response to therapy with bile acid sequestrants (BASs). However, there is no general agreement regarding its cutoff value and the test is not widely available. The aim of this review is to discuss the advantages and disadvantages of the SeHCAT test in clinical practice

Subthreshold psychiatric psychopathology in Functional gastrointestinal disorders: Can it be the bridge between gastroenterology and psychiatry?

Background and Aims: Functional gastrointestinal disorders (FGDs) are multifactorial disorders of the gut-brain interaction. This study investigated the prevalence of Axis I and spectrum disorders in patients with FGD and established the link between FGDs and psychopathological dimensions. Methods: A total of 135 consecutive patients with FGD were enrolled. The symptoms' severity was evaluated using questionnaires, while the psychiatric evaluation by clinical interviews established the presence/absence of mental (Diagnostic and Statistical Manual-4th edition, Axis I Diagnosis) or spectrum disorders. Results: Of the 135 patients, 42 (32.3%) had functional dyspepsia, 52 (40.0%) had irritable bowel syndrome, 21 (16.2%) had functional bloating, and 20 (15.4%) had functional constipation. At least one psychiatric disorder was present in 46.9% of the patients, while a suprathreshold panic spectrum was present in 26.2%. Functional constipation was associated with depressive disorders (p < 0.05), while functional dyspepsia was related to the current major depressive episode (p < 0.05). Obsessive-compulsive spectrum was correlated with the presence of functional constipation and irritable bowel syndrome (p < 0.05). Conclusion: The high prevalence of subthreshold psychiatric symptomatology in patients with FGD, which is likely to influence the expression of gastrointestinal symptoms, suggested the usefulness of psychological evaluation in patients with FGDs

Neuroendocrine Dysregulation in Irritable Bowel Syndrome Patients: A Pilot Study

BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is a multifactorial disorder, involving dysregulation of brain-gut axis. Our aim was to evaluate the neuroendocrine activity in IBS. METHODS: Thirty IBS and 30 healthy subjects were enrolled. Psychological symptoms were evaluated by questionnaires. Urinary 5-hydroxyindoleacetic acid (5-HIAA), plasma serotonin, endothelin, neuropeptide Y (NPY), plasma, and urinary cortisol levels were evaluated. Fourteen IBS subjects underwent microneurography to obtain multiunit recordings of efferent postganglionic muscle sympathetic nerve activity (MSNA). RESULTS: Prevalent psychological symptoms in IBS were maladjustment (60%), trait (40%) and state (17%) anxiety, obsessive compulsive-disorders (23%), and depressive symptoms (23%). IBS showed increased NPY (31.9 [43.7] vs 14.8 [18.1] pmol/L, P = 0.006), serotonin (214.9 [182.6] vs 141.0 [45.5] pg/mL, P = 0.010), and endothelin [1.1 [1.4] vs 2.1 [8.1], P = 0.054], compared to healthy subjects. Moreover, plasma NPY, endothelin, cortisol and serotonin, and urinary 5-HIAA were associated with some psychological disorders (P &lt; 0.05). Despite a similar resting MSNA, after cold pressor test, IBS showed a blunted increase in MSNA burst frequency (+4.1 vs +7.8 bursts/minute, P = 0.048; +30.1% vs +78.1%, P = 0.023). Baseline MSNA tended to be associated with urinary cortisol (ρ = 0.557, P = 0.059), and moreover, changes in heart rate and MSNA after mental stress were associated with urinary (ρ = 0.682, P = 0.021) and plasma cortisol (ρ = 0.671, P = 0.024), respectively. CONCLUSION: Higher concentrations of endothelin, NPY, and serotonin were found to be associated with some psychological disorders in IBS patients together with an altered cardiovascular autonomic reactivity to acute stressors compared to healthy subjects

Treatment and follow-up of a domestic ferret (Mustela putorius furo) with clinical leishmaniosis caused by Leishmania infantum

Leishmania infantum infection including treatment and follow up in domestic animals other than dogs and cats has not been described at this moment. This article describes the anti-Leishmania treatment and follow-up of a ferret (Mustela putorius furo) with leishmaniosis. A combined therapeutic protocol established for the patient, not yet approved for ferrets, was a combination of meglumine antimoniate plus allopurinol. A follow-up was established monthly during the first year in order to monitor the health condition of the patient. Six months after commencing allopurinol therapy, xanthine crystalluria was observed in urine sediment with no other urine alterations detected by urine analysis. The ferret worsened progressively with diarrhoea and weight loss after cohabiting with another ferret diagnosed with cryptosporidiosis. Cryptosporidium parvum was isolated in faecal samples from the patient detected by three different methods including Ziehl-Neelsen staining, a qualitative test to detection of C. parvum antigens and finally a specific molecular analysis to characterize the species. To the best of the authors´ knowledge, this is the first report providing information about anti-Leishmania protocol therapy used and follow-up in a domestic ferret with clinical leishmaniosis. Veterinarians practicing in endemic areas should be aware of this infection in ferrets at risk and their susceptibility especially when immunosuppressive conditions are present

Colangio-pancreatografia retrograda endoscopica (ERCP): studio osservazionale monocentrico di una casistica decennale (2009-2019). Stratificazione delle complicanze per fasce di eta e fattori di rischio.

La colangio-pancreatografia endoscopica retrograda (ERCP) è una metodica che permette la diagnosi e soprattutto il trattamento di innumerevoli patologie bilio-pancreatiche.In molte situazioni cliniche l'ERCP rappresenta l'unica alternativa alla chirurgia che in ambito bilio-pancreatico è gravata da elevata mortalità e complicanze. Nonostante la procedura sia relativamente sicura e meno invasiva di un intervento chirurgico questa può esitare in alcune complicanze come la pancreatite, il sanguinamento e la perforazione. Con il progressivo invecchiamento della popolazione l'ERCP è diventata una procedura sempre più utilizzata nella fascia di popolazione anziana in cui, a causa della frequente coesistenza di comorbilità, potremmo aspettarci una maggiore incidenza di complicanze. Il nostro studio ha valutato l’incidenza delle complicanze stratificando i pazienti per età; oltre a questo ha valutato fattori di rischio legati alla tecnica endoscopica e l’utilizzo di una profilassi farmacologica come fattore di protezione. I risultati ottenuti dal nostro studio sembrano avvalorare l’ipotesi secondo la quale l’età non rappresenterebbe un chiaro fattore di rischio per le complicanze in ERCP. Il Diclofenac somministrato prima della procedura rappresenta un fattore di protezione per pancreatite post procedurale. Manovre endoscopiche come il pre-cut, l'incannulazione accidentale del Wirsung e l'incannulazione difficile costituiscono invece dei fattori di rischio per complicanze

Lactobacillus Casei DG® in Patients with Irritable Bowel Syndrome: Not Only a Change of the Gut Microbiota. A Pilot Study

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Bioelectrical impedance vector analysis in patients with irritable bowel syndrome on a low FODMAP diet: a pilot study

Background: The aim of this study was to determine the effects of a low fermentable oligo-, di- and monosaccharides and polyols (FODMAP) diet on the nutritional status and body composition, abdominal symptoms, quality of life, anxiety/depression and sleep quality of patients with irritable bowel syndrome (IBS). Methods: Consecutive patients were given a low FODMAP diet for 8 weeks. At baseline and after 8 weeks, blood tests were taken to evaluate nutritional status and a bioelectrical impedance analysis was performed to assess body composition. Anthropometric data, IBS Symptom Severity Score, results of a bowel habits questionnaire, Bristol Stool Chart classification, SF36, Hamilton Depression Anxiety Scale outcome and Pittsburgh Sleep Quality Index were also recorded. During the 8-week diet period, the patients were phoned periodically by the nutritionist to verify their compliance. Results: Twenty-six IBS patients with a mean age of 46.2 ± 13.8 years were studied. After 8 weeks, there were no abnormalities in anthropometric data, bioelectrical impedance parameters and blood tests. The patients’ IBS Symptom Severity Score improved (305.2 ± 84.1 vs 156.3 ± 106.4; p < 0.0001), as did bowel habits, Bristol Stool Chart classification, quality of life and HADS anxiety score, whereas sleeping quality and depression were unchanged. The degree of relief from symptoms and satisfaction with the diet was high. Conclusions: A low FODMAP diet improved IBS symptoms without effects on nutritional status and body composition