Changes of blood biochemistry in the rabbit animal model in atherosclerosis research; a time- or stress-effect

<p>Abstract</p> <p>Background</p> <p>Rabbits are widely used in biomedical research and especially as animal models in atherosclerosis studies. Blood biochemistry is used to monitor progression of disease, before final evaluation including pathology of arteries and organs. The aim of the present study was to assess the consistency of the biochemical profile of New Zealand White rabbits on standard diet from 3 to 6 months of age, during which they are often used experimentally.</p> <p>Methods and results</p> <p>Eight conventional male 3-month-old New Zealand White rabbits were used. Blood samples were taken at baseline, 1, 2 and 3 months later. Plasma glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triacylglycerol concentrations, and alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase activities and malondialdehyde were measured. Statistically significant time-related changes were observed in glucose, total cholesterol and triacylglycerol, which were not correlated with aortic lesions at 6 months of age. Similarly, hepatic enzyme activity had significant time-related changes, without a corresponding liver pathology.</p> <p>Conclusions</p> <p>Age progression and stress due to single housing may be the underlying reasons for these biochemistry changes. These early changes, indicative of metabolic alterations, should be taken into account even in short-term lipid/atherosclerosis studies, where age and standard diet are not expected to have an effect on the control group of a study.</p

Comparative antilipidemic effect of N-acetylcysteine and sesame oil administration in diet-induced hypercholesterolemic mice

<p>Abstract</p> <p>Background</p> <p>There is an increasing number of novel antilipidemic therapies under consideration. The putative hypolipidemic effect of N-acetylcysteine (NAC) and sesame oil was studied in a mouse model of dietary-induced hypercholesterolemia.</p> <p>Methods</p> <p>Male C57bl/6 mice were assigned to the following groups: (NC) control group, (HC) group receiving test diet supplemented with 2% cholesterol and 0.5% cholic acid for 8 weeks, (HCN) group receiving the test diet with NAC supplementation (230 mg/kg p.o.) and (HCS) group fed the test diet enriched with 10% sesame oil. Total serum cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides were assayed at the beginning and at the end of the experiment. Total peroxides and nitric oxide (NO) levels were measured in the serum at the end of the experiment. Hepatic and aortic lesions were evaluated by haematoxylin-eosin staining.</p> <p>Results</p> <p>Higher serum levels of total and LDL-cholesterol were recorded in all groups fed the high cholesterol diet. The HCN group presented reduced lipid levels compared to HC and HCS groups. No differences were observed between HCS and HC groups. Peroxide content in serum was markedly increased in mice consuming high cholesterol diet. NAC and sesame oil administration led to a significant decrease of serum lipid peroxidation in the levels of control group, whereas only NAC restored NO bioavailability. In terms of liver histology, the lesions observed in HCN group were less severe than those seen in the other high cholesterol groups.</p> <p>Conclusion</p> <p>Co-administration of NAC, but not sesame oil, restored the disturbed lipid profile and improved hepatic steatosis in the studied diet-induced hypercholesterolemic mice. Both agents appear to ameliorate serum antioxidant defense.</p

Differential effect of Pistacia vera extracts on experimental atherosclerosis in the rabbit animal model: an experimental study

<p>Abstract</p> <p>Background</p> <p>Lipid-enriched diets and oxidative stress are risk factors for the development of atherosclerosis. The effects of the methanolic (ME) and cyclohexane (CHE) extracts of the <it>Pistacia vera </it>nut, often included in the Mediterranean diet, were studied in the rabbit model of atherosclerosis.</p> <p>Methods and results</p> <p>Twenty-four New Zealand White rabbits received atherogenic diet (Control Group), supplemented with ME (Group ME) or CHE (Group CHE) for 3 months. Previously, a GC-MS and a UHPLC LC-DAD-ESI(-)-HRMS/MS method were developed to investigate the extracts' chemical profiles. Blood samples at baseline and monthly determined lipid profile, lipid peroxidation and liver function. The aorta, myocardium and liver were examined histologically at 3 months.</p> <p>Groups ME and CHE had significantly higher HDL- and non-significantly lower LDL-cholesterol median % changes from baseline than the Control Group. Triacylglycerol was significantly higher in Group CHE vs. Control. MDA values were significantly lower in Group ME vs. Control and CHE. ALT and AST were significantly higher in Group CHE vs. Control. γ-GT was lower in Group ME vs. Control. Aortic intimal thickness was significantly less in Groups ME and CHE vs. Control; Group ME atherosclerotic lesions were significantly less extensive vs. Groups Control and CHE. Only Group CHE had significant liver fatty infiltration.</p> <p>Conclusions</p> <p>During short-term administration concomitantly with atherogenic diet, both <it>P. vera </it>extracts were beneficial on HDL-, LDL-cholesterol and aortic intimal thickness. The ME additionally presented an antioxidant effect and significant decrease of aortic surface lesions. These results indicate that <it>P. vera </it>dietary inclusion, in particular its ME, is potentially beneficial in atherosclerosis management.</p

Giant pedunculated hepatocellular carcinoma with hemangioma mimicking intestinal obstruction

<p>Abstract</p> <p>Background</p> <p>Pedunculated hepatocellular carcinoma (P-HCC) has rarely been reported and is characteristically large and encapsulated. Only sporadic cases have been published, in which P-HCC was combined with other liver tumors (mostly benign), making the diagnosis difficult.</p> <p>Case presentation</p> <p>We report a patient who was admitted to our hospital with clinical features of intestinal obstruction and a palpable mass in the right iliac fossa. Ultrasound, computed tomography and magnetic resonance imaging demonstrated an encapsulated mass of unclear origin and characteristics of liver hemangioma. Laboratory tests revealed elevated α-fetoprotein (> 800 ng/ml) and cancer antigen 125 (> 51.2 U/ml). With a possible diagnosis of giant liver hemangioma, we proceeded to surgery. During surgery, a giant pedunculated tumor was discovered on the inferior surface of the right lobe of the liver, hanging free in the right abdominal cavity towards the right iliac fossa. The macroscopic appearance of the tumor was compatible with liver hemangioma. Tumor resection was performed at a safe distance, including the pedicle. The rest of the liver appeared normal. Histopathological examination revealed grade II and III HCC (according to Edmondson-Steiner's classification) with nodular configuration, central necrosis, and infiltration of the capsule. Underneath the tumor capsule, residual tissue of a cavernous hemangioma was recognized. The resection margins were free of neoplastic tissue.</p> <p>Conclusion</p> <p>This rare presentation of a giant P-HCC combined with a hemangioma with features of intestinal obstruction confirmed the diagnostic difficulties of similar cases, and required prompt surgical treatment. Therefore, patients benefit from surgical resection because both the capsule and the pedicle prevent vascular invasion, therefore improving prognosis.</p

A role for surgery in primary pancreatic B-cell lymphoma: a case report

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How to develop a national heart failure clinics network: a consensus document of the Hellenic Heart Failure Association

Heart failure (HF) is rapidly growing, conferring considerable mortality, morbidity, and costs. Dedicated HF clinics improve patient outcomes, and the development of a national HF clinics network aims at addressing this need at national level. Such a network should respect the existing health care infrastructures, and according to the capacities of hosting facilities, it can be organized into three levels. Establishing the continuous communication and interaction among the components of the network is crucial, while supportive actions that can enhance its efficiency include involvement of multidisciplinary health care professionals, use of structured HF-specific documents, such as discharge notes, patient information leaflets, and patient booklets, and implementation of an HF-specific electronic health care record and database platform

The immunomodulatory effect of physical - exercise training in cronic heart failure patients

Objectives: We sought to investigate the effects of physical training on circulating proinflammatory cytokines and the soluble apoptosis mediators Fas (sFas) and Fas ligand (sFasL) in patients with chronic heart failure (CHF). Background: Recent investigations have shown an overexpression of circulating proinflammatory cytokines and soluble apoptosis mediators in patients with CHF which may be related to their exercise intolerance and clinical deterioration. Methods: Plasma levels of tumor necrosis factor alpha (TNF alpha), soluble TNF receptors I and II (sTNF-RI and sTNF-RII respectively), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), sFas and sFasL were measured in 24 patients with stable CHF (New York Heart Association functional class II/III left ventricular ejection fraction 23.2±1.3%) and in 20 normal control subjects before and after a 12 week program of physical training in a randomized crossover design. Functional status of patients with CHF was evaluated by using a cardiorespiratory exercise test to measure peak oxygen consumption (VO₂max). Results: Physical training produced a significant reduction in plasma levels of TNF alpha (7.5±1.0 pg/ml vs 4.6±0.7 pg/ml, p<0.001) sTNF-RI (3.3±0.2 ng/ml vs 2.7±0.2 ng/ml, p<0.005), sTNF-RII (2.6±0.2 ng/ml vs 2.3±0.2 ng/ml, p=0.06), IL-6 (8.3±1.2 pg/ml vs 5.9±08 pg/ml, p<0.005), sIL-6R (34.0±3.0 ng/ml vs 29.2±3.0 ng/ml, p<0.01), sFas (5.5±0.7 ng/ml vs 4.5±0.8 ng/ml, p=0.05) and sFasL (34.9±5.0 pg/ml vs 25.2±4.0 pg/ml, p<0.05) as well as a significant increase in VO₂max (16.3±0.7 ml/kg per min vs 18.7±0. ml/kg per min p<0.001). Good correlations were found between a training-induced increase in VO₂max and a training induced reduction in levels of the proinflammatory cytokine TNF alpha (r = -0 54, p<0.01) and the apoptosis inducer sFasL (r= -0.57, p<0.005) in patients with CHF. In contrast, no significant difference in circulating cytokines and apoptotic markers was found with physical training in normal subjects. Conclusions: Physical training reduces plasma levels of proinflammatory cytokines and the sFas/sFasL system in patients with CHF. These immunomodulatory effects may be related to the training induced improvement in functional status of patients with CHF.Η εκδήλωση της καρδιακής ανεπάρκειας χαρακτηρίζεται από την ενεργοποίηση του νευροορμονικού συστήματος και από την υπερδραστηριότητα της φλεγμονώδους και της αποπτωτικής διαδικασίας. Οι παράγοντες αυτοί συμμετέχουν στην περαιτέρω επιδείνωση του συνδρόμου ιδιαίτερα όσον άφορα στη λειτουργία του ενδοθηλίου και των σκελετικών μυών. Σκοπός της διατριβής ήταν να διερευνήσει την επίδραση της σωματικής άσκησης στη φλεγμονώδη ενεργοποίηση (στα επίπεδα των κυτοκινών TNF-α και IL-6) στην αποπτωτική διεργασία (Fas/FasLigand) καθώς και αν συσχετίζεται η βελτίωση στη λειτουργική ικανότητα των ασθενών που ασκήθηκαν με τη μείωση του παράγοντα νεκρώσεως όγκου α (TNF-α) και της ιντερλευκίνης 6 (IL-6) καθώς και των αποπτωτικών δεικτών (Fas/FasLigand). Μέθοδος: Μελετήσαμε είκοσι τέσσερις ασθενείς με χρόνια καρδιακή ανεπάρκεια οι οποίοι είχαν ηλικία 55±2 έτη και βρίσκονταν σε λειτουργικό στάδιο II-III κατά ΝΥΗΑ με μέσο κλάσμα εξωθήσεως 23±2% καθώς και είκοσι υγιείς-μάρτυρες (control). Αρχικά έγιναν οι βασικές μετρήσεις (baseline) και στη συνέχεια οι ασθενείς ασκήθηκαν για διάστημα 12 εβδομάδων ή απείχαν από κάθε άσκηση σύμφωνα με τυχαιοποιημένο διασταυρούμενο σχεδιασμό ενώ επανεκτιμήθηκαν μετά την 1η και 2η αντίστοιχα περίοδο. Οι ασθενείς υποβλήθηκαν σε καρδιοαναπνευστική κόπωση για να εκτιμηθεί η λειτουργική τους ικανότητα (μέτρηση της μέγιστης κατανάλωσης οξυγόνου VO₂max). Αποτελέσματα: Οι ασθενείς με χρόνια καρδιακή ανεπάρκεια που ακολούθησαν το πρόγραμμα σωματικής άσκησης (training) εμφάνισαν σημαντική μείωση στις κυκλοφορούσες προφλεγμονδώδεις κυτοκίνες σε σύγκριση με τους ασθενείς που απείχαν από την άσκηση (detraining). Παρατηρήθηκε σημαντική μείωση στις συγκεντρώσεις στον ορρό του TNF-α από 7.5±1.0 σε 4.6±0.7 pg/ml, p<0.001 καθώς επίσης και του διαλυτού (s) υποδοχέα του sTNF-RI από 3.3±0.2 σε 2.7±0.2 ng/ml, p<0.005 ενώ οριακή ήταν η μείωση για τον υποδοχέα sTNF-RII από 2.6±0.2 σε 2.3±0.2 ng/ml, p=0.06. Επίσης, καταγράφηκε σημαντική μείωση της IL-6 από 8.3±1.2 σε 5.9±0.8 pg/ml, p<0.005 καθώς και του διαλυτού υποδοχέα της sIL-6R από 34.0±3.0 σε 29.2±3.0 ng/ml, p<0.01. Ο sFas ελαττώθηκε σημαντικά από 5.5±0.7 σε 4.5±0.8 ng/ml, p=0.05 και ο sFasL από 34.9±5.0 σε 25.2±4.0 pg/ml, p<0.05. Η ικανότητα για άσκηση βελτιώθηκε σημαντικά στους ασθενείς που ασκήθηκαν από 16.3±0.7 ml O₂/kg ανά min σε 18.7±0.8 ml O₂/kg ανά min p<0.001. Η αύξηση της μέγιστης κατανάλωσης οξυγόνου συσχετίστηκε με τη μείωση του TNF-α (r= -0.54, p<0.01) και του sFasL (r= -0 57, p<0.005). Οι κυτοκίνες και οι αποπτωτικοί δείκτες δεν μεταβλήθηκαν στους υγιείς μάρτυρες. Συμπέρασμα: Η εφαρμογή προγραμμάτων σωματικής άσκησης ελαττώνει την ανοσοφλεγμονώδη ενεργοποίηση που χαρακτηρίζει την παθοφυσιολογία του συνδρόμου της χρόνιας καρδιακής ανεπάρκειας γεγονός που πιθανώς σχετίζεται με τη βελτίωση της λειτουργικής ικανότητας των ασθενών αυτών

Controlled polymerization of histidine and synthesis of well-defined stimuli responsive polymers. Elucidation of the structure–aggregation relationship of this highly multifunctional material

We present the synthesis of the novel monomer Nim-trityl-protected N-carboxy anhydride of l-histidine (Trt-HIS-NCA) for the synthesis of poly(l-histidine) (PHIS). Kinetic studies of the ring opening polymerization of Trt-HIS-NCA followed first order kinetics, indicating that the polymerization is &quot;living&quot;. The high purity of the synthesized monomer along with the use of high vacuum techniques resulted in the controlled polymerization of histidine in a variety of macromolecular architectures exhibiting high degrees of molecular and compositional homogeneity. The conformation of poly(l-histidine) (PHIS) was studied at different pH values and temperatures by circular dichroism, revealing that it adopts a random coil conformation at low pH and temperatures, a β-sheet conformation at higher pH, and probably a broken β-sheet conformation at higher temperatures. We found that the pKa of the PHIS homopolymer depends on the molecular weight. Addition of hydrophobic amino acids randomly distributed along the PHIS chain hinders the organization of PHIS, resulting in the formation of the random coil conformation even at higher pH. The influence of either leucine (LEU) or γ-benzyl-l-glutamate (BLG) randomly distributed along the PHIS chain on the pKa and degree of protonation in the terpolymers revealed that although the pKa is lower, the protonation of PHIS increases at lower pH values, while it is lower at a higher pH as compared to that obtained for PHIS. The aggregates of PEO-b-P(HIS-co-PLEU(BLG)) in water were found to swell more by decreasing the pH and increasing the hydrophobic amino acids, and eventually become disrupted. Surprisingly, at pH = 7.4, the increase in temperature leads to lower aggregation of the PEO-b-PHIS due to the transition of the secondary structure. The results indicate that it is possible to fine-tune the protonation of PHIS as a function of pH and temperature, and thus to control the conditions where the aggregates will be disrupted, a prerequisite for drug and gene delivery applications. © 2014 the Partner Organisations