Πειραματική απομόνωση και μεταμόσχευση μεσεγχυματικών κυττάρων (mesenchymal stem cells) σε πειραματικό πρότυπο 50-60% ηπατεκτομής σε αρουραίους. Ειδική βιοχημική μελέτη

Η απώλεια του ηπατικού παρεγχύματος δύναται να προκληθεί από διάφορους παράγοντες, όπως οι ιογενείς ηπατίτιδες, οι φαρμακευτικοί και ηπατοτοξικοί παράγοντες, οι μεταβολικές νόσοι, το τραύμα του ήπατος, καθώς και από τις χειρουργικές επεμβάσεις ηπατεκτομής, και ενδέχεται να οδηγήσει σε ηπατική ανεπάρκεια, η οποία αποτελεί μία εκ των κυριότερων αιτιών νοσηρότητας και θνητότητας παγκοσμίως. Τη μόνη αποτελεσματική θεραπεία, μέχρι σήμερα, για την αντιμετώπιση της ηπατικής ανεπάρκειας αποτελεί η μεταμόσχευση του ήπατος, με τους συνοδούς, ωστόσο, περιορισμούς της, που περιλαμβάνουν την έλλειψη επαρκούς αριθμού μοσχευμάτων, όπως και την ανάγκη για λήψη ανοσοκατασταλτικής αγωγής εφ’όρου ζωής. Τα μεσεγχυματικά βλαστικά κύτταρα αποτελούν μία πολλά υποσχόμενη μέθοδο για την αντιμετώπιση της ηπατικής νόσου τελικού σταδίου, καθώς και της ηπατικής ανεπάρκειας. Πολυάριθμες μελέτες έχουν ήδη αποδείξει την αποτελεσματικότητα των μεσεγχυματικών βλαστικών κυττάρων, προερχόμενων εκ του μυελού των οστών, στην ενίσχυση της ηπατικής αναγέννησης. Ωστόσο, συγκεκριμένα χαρακτηριστικά των μεσεγχυματικών βλαστικών κυττάρων, προερχόμενων εκ του λιπώδους ιστού, τα καθιστούν μία άκρως ελκυστική εναλλακτική επιλογή, για την αντιμετώπιση της ηπατικής ανεπάρκειας. Τα μεσεγχυματικά βλαστικά κύτταρα εκ του λιπώδους ιστού βρίσκονται σε αφθονία εντός αυτού και μπορούν να συλλεχθούν με τη χρήση ελάχιστα επεμβατικών τεχνικών, με μεθόδους σχεδόν ανώδυνες. Επίσης, δημοσιευμένες πειραματικές μελέτες έχουν αποδείξει, πως τα μεσεγχυματικά βλαστικά κύτταρα εκ του λιπώδους ιστού εμφανίζουν μεγαλύτερη δέσμευση προς την ηπατική κυτταρική σειρά, όπως επίσης και υψηλότερο ρυθμό κυτταρικού πολλαπλασιασμού, σε σύγκριση με τα μεσεγχυματικά κύτταρα προερχόμενα εκ του μυελού των οστών. Τα ευρήματα της παρούσας μελέτης αποδεικνύουν πως η προ-μεταμοσχευτική διαφοροποίηση των μεσεγχυματικών βλαστικών κυττάρων, προερχόμενων εκ του λιπώδους ιστού, δεν αποτελεί αναγκαία προϋπόθεση για την θεραπευτική τους δράση, καθώς τα αδιαφοροποίητα μεσεγχυματικά βλαστικά κύτταρα είχαν επιτυχώς ενσωματωθεί εντός του εναπομείναντος ηπατικού παρεγχύματος ήδη από την 4η μετεγχειρητική ημέρα, και εξακολουθούσαν να παραμένουν εντοπισμένα και βιώσιμα μέχρι και την 15η μετεγχειρητική ημέρα, που αποτέλεσε και το τέλος της περιόδου παρακολούθησης. Την επιτυχή ενσωμάτωση των μεσεγχυματικών βλαστικών κυττάρων, προερχόμενων εκ του λιπώδους ιστού, εντός του εναπομείναντος ηπατικού παρεγχύματος, ακολούθησε μία σαφέστατη ενίσχυση του ρυθμού της ηπατικής αναγέννησης στα μεταμοσχευμένα πειραματόζωα, η οποία διήρκησε μέχρι και την 7η μετεγχειρητική ημέρα, συνοδευόμενη από μία σημαντική βελτίωση της, επαγόμενης από τη χειρουργική επέμβαση ηπατεκτομής, ιστολογικής βλάβης του εναπομείναντος παρεγχύματος, κατά την 7η και 15η μετεγχειρητική ημέρα. Αποδείχθηκε, επίσης, πως η μεταμόσχευση των αδιαφοροποίητων μεσεγχυματικών βλαστικών κυττάρων, συνοδεύθηκε από την ενίσχυση της συνθετικής ικανότητας του ήπατος, και από την σημαντική ενίσχυση της έκφρασης των γονιδίων που σχετίζονται με την ηπατική αναγέννηση, αλλά και των γονιδίων που εκφράζονται κατά τρόπο ειδικό στα ηπατικά κύτταρα. Έντονο είναι το ενδιαφέρον της επιστημονικής κοινότητας ως προς την ιδανική οδό μεταμόσχευσης των μεσεγχυματικών βλαστικών κυττάρων, καθώς και ως προς τον ιδανικό αριθμό αυτών. Τα ευρήματα της παρούσας μελέτης αποδεικνύουν, πως παρά το γεγονός ότι η ενδοπαρεγχυματική χορήγηση των μεσεγχυματικών κυττάρων, προερχόμενων εκ του λιπώδους ιστού, απέδωσε τα καλύτερα αποτελέσματα κατά την 4η και 7η μετεγχειρητική ημέρα, όσον αφορά στην ενίσχυση της ηπατικής αναγέννησης, συγκριτικά με τα αντίστοιχα μη μεταμοσχευμένα πειραματόζωα, εντούτοις δεν ανευρέθηκαν άλλες στατιστικά σημαντικές διαφορές μεταξύ των διαφορετικών μεταμοσχευμένων υπο-ομάδων, όσον αφορά στην ενίσχυση της ηπατικής αναγεννητικής διαδικασίας, ευρήματα που επιβεβαιώνονται στη διεθνή επιστημονική βιβλιογραφία. Επιπλέον, δεν αποδείχθηκαν στατιστικά σημαντικές διαφορές, μεταξύ των διαφορετικών υπο-ομάδων που μεταμοσχεύθηκαν με διαφορετικό αριθμό μεσεγχυματικών κυττάρων, όσον αφορά στην ενίσχυση της διαδικασίας της ηπατικής αναγέννησης. Δεδομένου του πολύτιμου, ελάχιστου διαθέσιμου χρόνου για την αντιμετώπιση της οξείας ηπατικής ανεπάρκειας, τα ευρήματα της παρούσας μελέτης αποκτούν ιδιαίτερο ενδιαφέρον, όταν επιπροβάλλονται σε κλινικό επίπεδο. Η πρώιμη ενσωμάτωση των μεταμοσχευμένων μεσεγχυματικών βλαστικών κυττάρων εντός του ηπατικού παρεγχύματος, που αποτελεί το όργανο – στόχο, ήδη από την 4η μετεγχειρητική ημέρα, και η έλλειψη προ-μεταμοσχευτικής διαφοροποίησής τους προς την ηπατοκυτταρική σειρά, γεγονός που απαιτεί κατ’ ελάχιστον δύο εβδομάδες για να ολοκληρωθεί, τα καθιστούν ιδανικά, σε κλινικά πλαίσια, για την αντιμετώπιση της οξείας ηπατικής ανεπάρκειας, καθώς όπως απέδειξε η παρούσα μελέτη, τα μεταμοσχευμένα μεσεγχυματικά κύτταρα συνέβαλαν αποτελεσματικά στην ενίσχυση της ηπατικής αναγέννησης, και της συνθετικής ικανότητας του ήπατος, δίχως να δαπανηθεί χρόνος για την προ-μεταμοσχευτική διαφοροποίησή τους, ο οποίος ενδέχεται να αποδειχθεί σωτήριος σε κλινικό επίπεδο.Loss of liver mass may be induced by several factors, such as hepatitis virus infection, drug and hepatotoxic chemicals administration, metabolic diseases, trauma, as well as surgical procedures in the liver, and can lead to liver failure (LF). LF is one of the leading causes of morbidity and mortality worldwide. The only effective treatment so far for acute and chronic LF is liver transplantation, with its associated limitations, including the shortage of liver donors and the need for continuous immunosuppression. Mesenchymal stem cells (MSCs) present a promising therapeutic method to alleviate end stage liver disease (ESLD) and LF. Although a number of reports have demonstrated the effectiveness of BM-MSCs in hepatic regeneration, certain characteristics of adipose tissue stem cells (ADSCs) render them as an attractive option for liver repopulation. ADSCs are in abundance and may be harvested with the use of minimally invasive procedures. Moreover, they show a stronger commitment to hepatic lineage, as well as higher rates of proliferation, compared with BM-MSCs. The findings of the present study demonstrated that a pre-transplantation differentiation of ADSCs towards the hepatic lineage is not a prerequisite for a successful outcome, since the transplanted undifferentiated ADSCs were already successfully engrafted into the liver parenchyma from the 4th postoperative day (POD), and were still localized in the liver till the 15th POD, which was the end of the follow-up period. The successful engraftment of the transplanted ADSCs into the liver parenchyma was followed by a definitive enhancement of the liver regeneration rate in the transplanted animals till the 7th POD, accompanied by an amelioration of the histopathologic damage on the 7th and 15th POD, as well as by a promotion of the synthetic ability of the liver, and an up-regulation of the expression of liver regeneration and liver-specific genes, in the transplanted animals. Several studies have focused on the optimal route of transplantation of MSCs, and the optimal number of transplanted MSCs. The present study demonstrated that, although the intrahepatic (IH) administration of ADSCs rendered the best results, in promoting the liver regeneration process, compared with the respective control group on the 4th and 7th POD of sacrifice, no other specific significant differences were identified among the transplanted animals, as for the number and route of administration of ADSCs, a finding also supported by the aforementioned results, as well as several other studies. There is limited time in treating and saving a patient, suffering from acute liver failure (ALF). In this context, the results of the present study are of particular value, when applied to a clinical setting. The cornerstone of our study is the successful transplantation and localization of ADSCs into the liver parenchyma, without a previous in vitro differentiation towards the hepatic lineage, which needs at least two weeks to complete. This results in a faster and definitive enhancement of the liver regeneration process, as well as in an up-regulation of the synthetic ability of the liver, when compared with the non–transplanted groups of animals, without at the same time sacrificing any time in the differentiation process, which may be proven life – salutary, in the clinical context

An outbreak of hemodialysis catheter-related bacteremia with sepsis caused by Streptococcus agalactiae in a hemodialysis unit

AbstractBackgroundRates of invasive group B Streptococcus (GBS; Streptococcus agalactiae) disease in adults are on the rise. Invasive GBS disease can be community- or healthcare-associated. We report an outbreak of GBS catheter-related bacteremia in a hemodialysis (HD) unit.Materials and methodsTwo patients undergoing HD at the same outpatient HD unit were admitted on the same day (within a few hours of each other) with catheter-related GBS bacteremia. A retrospective study was undertaken at the HD unit to address risk factors for febrile illness on the last HD session day. A detailed questionnaire was completed by all HD patients treated on the same day as the two GBS patients and by all members of the nursing and medical staff. Medical and nursing records of the HD unit were reviewed, as well as infection control and catheter care practices. Patients and staff members submitted swabs for culture.ResultsNo rectal or vaginal culture of any HD patient or staff member was positive for GBS. The development of recent febrile disease was significantly associated with the presence of a hemodialysis catheter (p=0.028) and care for more than 30min by a specific nurse during the last two HD sessions (p=0.007).ConclusionsWe speculate that the GBS strain was transmitted from one patient to the other through the hands of medical personnel. No such outbreak has ever been reported in HD patients. The importance of strict infection control practices in HD units and the avoidance of catheters for long-term HD should be emphasized

Peptidergic modulation of motor neuron output via CART signaling at C bouton synapses

Funding: This work was supported by the General Secretariat for Research and Technology (ARISTEIA II 4257, L.Z.), Fondation SANTE (L.Z.), a Marie Curie Re-Integration Grant (268323, L.Z.), the Hellenic Foundation for Research and Innovation (spinMNALS, 4013, L.Z.) and by a St. Andrews Restarting Research Fund (S.A.S. and G.B.M.). S.A.S. was funded by a Royal Society Newton International Fellowship (NIF/R1/180091) and a Natural Sciences and Engineering Research Council of Canada (NSERC) Postdoctoral Fellowship (NSERC-PDF-517295-2018) and M.M. by the National Scholarship Foundation (IKY).The intensity of muscle contraction, and therefore movement vigour, needs to be adaptable to enable complex motor behaviors. This can be achieved by adjusting the properties of motor neurons, which form the final common pathway for all motor output from the central nervous system. Here we identify novel roles for a neuropeptide, Cocaine and Amphetamine Regulated Transcript (CART), in the control of movement vigour. We reveal distinct, but parallel mechanisms by which CART and acetylcholine, both released at C bouton synapses on motor neurons, selectively amplify the output of subtypes of motor neurons that are recruited during intense movement. We find that mice with broad genetic deletion of CART or selective elimination of acetylcholine from C boutons exhibit deficits in behavioral tasks that require higher levels of motor output. Overall, these data uncover novel spinal modulatory mechanisms that control movement vigour to support movements that require a high degree of muscle force.Publisher PDFPeer reviewe

Reasons of Singles for Being Single:Evidence from Brazil, China, Czech Republic, Greece, Hungary, India, Japan and the UK

The current research aimed to examine the reasons people are single, that is, not in an intimate relationship, across eight different countries—Brazil, China, Czech Republic, Greece, Hungary, India, Japan, and the UK. We asked a large cross-cultural sample of single participants (N = 6,822) to rate 92 different possible reasons for being single. These reasons were classified into 12 factors, including one’s perceived inability to find the right partner, the perception that one is not good at flirting, and the desire to focus on one’s career. Significant sex and age effects were found for most factors. The extracted factors were further classified into three separate domains: Perceived poor capacity to attract mates, desiring the freedom of choice, and currently being in between relationships. The domain structure, the relative importance of each factor and domain, as well as sex and age effects were relatively consistent across countries. There were also important differences however, including the differing effect sizes of sex and age effects between countries

Short-term effects of manual therapy plus capacitive and resistive electric transfer therapy in individuals with chronic non-specific low back pain : a randomized clinical trial study

Background and Objectives: Chronic non-specific low back pain (CNSLBP) is defined as back pain that lasts longer than 12 weeks. Capacitive and resistive electric transfer (TECAR) therapy utilizes radiant energy to generate endogenous heat and is widely used for the treatment of chronic musculoskeletal pain. The aim of this study was to investigate the efficacy of manual therapy (MT) program combined with TECAR therapy in individuals with CNSLBP. Materials and Methods: Sixty adults with CNSLBP were randomly divided equally into three groups. The first group followed an MT protocol in the lumbar region (MT group), the second group followed the same MT protocol combined with TECAR therapy (MT + TECAR group) using a conventional capacitive electrode as well as a special resistive electrode bracelet, and the third group (control group) received no treatment. Both intervention programs included six treatments over two weeks. Pain in the last 24 h with the Numeric Pain Rating Scale (NPRS), functional ability with the Roland–Morris Disability Questionnaire (RMDQ), pressure pain threshold (PPT) in the lumbar region with pressure algometry, and mobility of the lumbo-pelvic region through fingertip-to-floor distance (FFD) test were evaluated before and after the intervention period with a one-month follow-up. Analysis of variance with repeated measures was applied. Results: In the NPRS score, both intervention groups showed statistically significant differences compared to the control group both during the second week and the one-month follow-up (p 0.05). Conclusions: The application of an MT protocol with TECAR therapy appeared more effective than conventional MT as well as compared to the control group in reducing pain and disability and improving PPT in individuals with CNSLBP. No further improvement was noted in the mobility of the lumbo-pelvic region by adding TECAR to the MT intervention

Increased glucocorticoid receptor expression in sepsis is related to heat shock proteins, cytokines, and cortisol and is associated with increased mortality

BACKGROUND: The purposes of this study are to examine if the human glucocorticoid receptor (hGR) isoform-α mRNA and hGR protein expressions are deficient in the acute phase of sepsis (S) compared to systemic inflammatory response syndrome (SIRS) and healthy subjects (H) and to evaluate if the hGRα and hGR alterations are associated with cortisol changes and if they are related to (1) extracellular and intracellular heat shock proteins (HSP) 72 and 90α; (2) ACTH, prolactin, and interleukins (ILs); and (3) outcome. METHODS: Patients consecutively admitted to a university hospital intensive care unit (ICU) with S (n = 48) or SIRS (n = 40) were enrolled in the study. Thirty-five H were also included. Total mRNA was isolated from peripheral blood samples and cDNA was prepared. RT-PCR was performed. Intracellular hGR and HSP expression in monocytes and/or neutrophils was evaluated using four-colour flow cytometry. Serum prolactin, ACTH, and cortisol concentrations were also measured. ELISA was used to evaluate serum ILs and extracellular (e) HSPs (eHSP72, eHSP90α). RESULTS: hGR protein was higher in S compared to H and SIRS; hGRα mRNA was higher in S compared to H (p < 0.05). In sepsis, hGR protein and eHSP72 were higher among non-survivors compared to survivors (p < 0.05). The hGR MFI and hGRα mRNA fold changes were significantly related to each other (r (s) = 0.64, p < 0.001). Monocyte hGR protein expression was positively correlated with extracellular and intracellular HSPs, cortisol, and ILs and negatively to organ dysfunction (p < 0.05). HSPs, hGR, and cortisol were able to discriminate sepsis from SIRS (AUROC > 0.85, p < 0.05). In sepsis, monocyte-hGR protein and eHSP72 were strong predictors of mortality (AUROC > 0.95, p < 0.04). CONCLUSIONS: Acute-phase sepsis is associated with increased hGR expression and cortisol concentrations, possibly implying no need for exogenous steroids. At this stage, hGR is able to predict sepsis and outcome and is related to stress-activated bio-molecules and organ dysfunction

Undifferentiated Adipose Tissue Stem Cell Transplantation Promotes Hepatic Regeneration, Ameliorates Histopathologic Damage of the Liver, and Upregulates the Expression of Liver Regeneration- and Liver-Specific Genes in a Rat Model of Partial Hepatectomy

Objective. Adipose tissue stem cells (ADSCs) present a promising therapeutic method to alleviate liver failure (LF). The purpose of this prospective study was to evaluate the efficacy of undifferentiated ADSC transplantation on liver regeneration and on the expression of liver regeneration- and liver-specific genes, following 60% partial hepatectomy (PHx). Methods. Sixty female rats were subjected to PHx and were transplanted with 106 or 2 × 106 ADSCs, either into the portal vein (PV) or into the hepatic parenchyma. Animals of the control group were not transplanted and served as controls. Animals were sacrificed on the 4th, the 7th, or the 15th postoperative day (POD). Results. The transplanted ADSCs were successfully engrafted into the liver parenchyma and ameliorated the histopathologic damage on the 7th and 15th POD. All transplanted animals demonstrated a significantly higher liver regeneration rate on the 4th and 7th POD, compared with the control group. The expression of hepatocyte growth factor, α-fetoprotein, tyrosine aminotransferase, hepatocyte nuclear factor 4a, and cytochrome P450 1A2 was significantly upregulated, compared with the control group. Conclusions. Although undifferentiated, ADSC transplantation significantly enhanced the liver regeneration process. These findings may be proven clinically valuable, especially in cases of acute LF

Antiphospholipid Syndrome and Pregnancy-Diagnosis, Complications and Management: An Overview

Antiphospholipid syndrome which is also known as APS is an autoimmune disease which represents an acquired form of thrombophilia. The etiology of APS remains unknown. This disorder occurs when the immune system mistakenly attacks some of the normal human proteins and manifests itself as recurrent arterial or venous thrombosis and it could emerge after abortions or in recurrent pregnancy loss. In APS, the body produces the wrong antibodies against phospholipid-binding proteins, that is present in the blood and plays an important role in coagulation. Antibodies are specific proteins that usually target and neutralize the body’s invaders, such as viruses and bacteria. When antibodies attack phospholipid-binding proteins, blood clots abnormally. Specifically, it could cause blood clots in veins or arteries leading to stroke and various pregnancy complications such as: endometrial death, miscarriage, preeclampsia, intrauterine growth restriction and prematurity. APS is divided into primary and secondary, which is associated with autoimmune diseases and more often with systemic lupus erythematosus (SLE), while antibodies against cardiolipin are detected in many other conditions (infections, malignancies, drugs, etc.). The symptoms of APS, in addition to arterial and/or venous thrombosis and pregnancy complications, are multisystemic and the differential diagnosis of the primary APS from the secondary, in the context of SLE, is of particular clinical interest and is subject of this literature review

Twin Pregnancies Labour Modus and Timing

Twin pregnancies are categorized according to three factors, zygosity, chorionicity and amnionicity. Dizygotic twins are always dichorionic and diamniotic, where each twin has its own chorionic and amniotic sac. Monozygotic twins account for 1/3 of twin pregnancies and show higher morbidity and mortality. In monozygotic twins, chorionicity and amnionicity are determined by the time of zygote division. Chorionicity and amnionicity determine the risks of twin pregnancy. Morbitidies are shown notable decreasing tendency depending on improving of high risk obstetric and neonatal care, however is still discussed the optimum labour management in twin pregnancies Vaginal delivery in twin pregnancies is possible when both have cephalic presentation and in the late weeks of pregnancy during which the risks of prematurity are minimized. The aim of this review was the assessment and evaluation the impact of the labour modus and timing of termination of twin pregnancies due to rise of their occurrence based on scientific aspects of the new published literature on perinatal outcome