Portocaval shunt can optimize transhepatic flow following extended hepatectomy: a short-term study in a porcine model.

The aim of this study was to evaluate whether the portocaval shunt (PCS) corrects these unwanted changes in transhepatic flow after extended hepatectomy (EH). Forty female Landrace pigs were divided into two main groups: (A) EH (75%) and (B) no EH. Group A was divided into 3 subgroups: (A1) EH without PCS; (A2) EH with side-to-side PCS; and (A3) EH with end-to-side PCS. Group B was divided into 2 subgroups: (B1) side-to-side PCS and (B2) end-to-side PCS. HAF, PVF, and PVP were measured in each animal before and after the surgical procedure. EH increased the PVF/100 g (173%, p < 0.001) and PVP (68%, p < 0.001) but reduced the HAF/100 g (22%, p = 0.819). Following EH, side-to-side PCS reduced the increased PVF (78%, p < 0.001) and PVP (38%, p = 0.001). Without EH, side-to-side PCS reduced the PVF/100 g (68%, p < 0.001) and PVP (12%, p = 0.237). PVP was reduced by end-to-side PCS following EH by 48% (p < 0.001) and without EH by 21% (p = 0.075). PCS can decrease and correct the elevated PVP and PVF/100 g after EH to close to the normal values prior to resection. The decreased HAF/100 g in the remnant liver following EH is increased and corrected through PCS.

Cytokine secretion pattern in treatment of lymphocytes of multiple sclerosis patients with fumaric acid esters.

The present study was performed to investigate the effects of dimethylfumarate (DMF) and methylhydrogen fumarate (MHF) on the cytokine pattern of peripheral blood mononuclear cells (PBMCs) of multiple sclerosis (MS) patients. The PBMCs from patients and healthy controls were stimulated with myelin basic protein (MBP) or phytohemagglutinin (PHA) and cultured in the presence of DMF and MHF. The percentage of CD4+IL-4+ and CD4+IFN-γ+ cells was determined by means of intracellular cytokine staining. CD4+IL-4+ cells were significantly increased in the presence of DMF and MHF when PBMCs were stimulated by MBP (P < 0.003). The same significant result was obtained by PHA stimulation (P < 0.049). In terms of CD4+IFN-γ+ cells, the percentage of cells did not significantly differ between the cultures stimulated with MBP or PHA in the presence and absence of the drugs. Results of MBP stimulation in control group also showed a significant increase in CD4+IL-4+ cells in the presence of DMF and MHF. In comparison between patient and control groups, no statistically significant changes were observed. In conclusion, both DMF and MHF effectively increased IL-4 production, whereas they did not significantly change IFN-γ level, indicating the role of these drugs in increasing the production of beneficial cytokines such as IL-4.

Hepatitis B core-based virus-like particles: A platform for vaccine development in plants.

Virus-like particles (VLPs) are a class of structures formed by the self-assembly of viral capsid protein subunits and contain no infective viral genetic material. The Hepatitis B core (HBc) antigen is capable of assembling into VLPs that can elicit strong immune responses and has been licensed as a commercial vaccine against Hepatitis B. The HBc VLPs have also been employed as a platform for the presentation of foreign epitopes to the immune system and have been used to develop vaccines against, for example, influenza A and Foot-and-mouth disease. Plant expression systems are rapid, scalable and safe, and are capable of providing correct post-translational modifications and reducing upstream production costs. The production of HBc-based virus-like particles in plants would thus greatly increase the efficiency of vaccine production. This review investigates the application of plant-based HBc VLP as a platform for vaccine production.

Comparative Analysis of the Discriminatory Performance of Different Well-Known Risk Assessment Scores for Extended Hepatectomy.

The aim of this study was to assess and compare the discriminatory performance of well-known risk assessment scores in predicting mortality risk after extended hepatectomy (EH). A series of 250 patients who underwent EH (≥5 segments resection) were evaluated. Aspartate aminotransferase-to-platelet ratio index (APRI), albumin to bilirubin (ALBI) grade, predictive score developed by Breitenstein et al., liver fibrosis (FIB-4) index, and Heidelberg reference lines charting were used to compute cut-off values, and the sensitivity and specificity of each risk assessment score for predicting mortality were also calculated. Major morbidity and 90-day mortality after EH increased with increasing risk scores. APRI (86%), ALBI (86%), Heidelberg score (81%), and FIB-4 index (79%) had the highest sensitivity for 90-day mortality. However, only the FIB-4 index and Heidelberg score had an acceptable specificity (70% and 65%, respectively). A two-stage risk assessment strategy (Heidelberg-FIB-4 model) with a sensitivity of 70% and a specificity 86% for 90-day mortality was proposed. There is no single specific risk assessment score for patients who undergo EH. A two-stage screening strategy using Heidelberg score and FIB-4 index was proposed to predict mortality after major liver resection.

Roles of GM-CSF in the Pathogenesis of Autoimmune Diseases: An Update.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was first described as a growth factor that induces the differentiation and proliferation of myeloid progenitors in the bone marrow. GM-CSF also has an important cytokine effect in chronic inflammatory diseases by stimulating the activation and migration of myeloid cells to inflammation sites, promoting survival of target cells and stimulating the renewal of effector granulocytes and macrophages. Because of these pro-cellular effects, an imbalance in GM-CSF production/signaling may lead to harmful inflammatory conditions. In this context, GM-CSF has a pathogenic role in autoimmune diseases that are dependent on cellular immune responses such as multiple sclerosis (MS) and rheumatoid arthritis (RA). Conversely, a protective role has also been described in other autoimmune diseases where humoral responses are detrimental such as myasthenia gravis (MG), Hashimoto's thyroiditis (HT), inflammatory bowel disease (IBD), and systemic lupus erythematosus (SLE). In this review, we aimed for a comprehensive analysis of literature data on the multiple roles of GM-CSF in autoimmue diseases and possible therapeutic strategies that target GM-CSF production.

MicroRNA-92a Drives Th1 Responses in the Experimental Autoimmune Encephalomyelitis.

Dysregulation of microRNAs (miRNAs) has been linked to the progress of a number of autoimmune diseases including multiple sclerosis (MS), and its animal model, experimental autoimmune encephalomyelitis (EAE). IFN-γ-producing Th1 cells are major players in MS/EAE pathogenesis. It is known that differentiation of T cells towards the Th1 phenotype is influenced by various factors including miRNAs. The miR-92a shows substantial upregulation in MS; however, little is known about its role in the development of autoimmune and inflammatory responses. Herein, we investigated the role of miR-92a in the pathogenesis of MS, focusing on its potential effects on differentiation of Th1 cells. The expression levels of miR-92a were assessed in the spinal cord tissues and splenocytes from mice with EAE using real-time RT-PCR. Next, using transfection with miR-92a mimic sequences, the potential involvement of miR-92a in Th1 polarization was investigated by flow cytometric analysis. Moreover, the expression levels of miR-92a targets were explored in spinal cord tissues of EAE mice. miR-92a expression was enhanced in mouse spinal cord samples at the peak of EAE disease. Overexpression of miR-92a in splenocytes led to increased differentiation of Th1 cells compared with cells transfected with negative control sequences. Enhanced miR-92a expression was accompanied by reduced expression TSC1 or DUSP10, predicted miR-92a targets, in EAE spinal cords. Our data point to a potential role for miR-92a in neuroinflammatory responses in EAE. Our results indicate that miR-92a might affect Th1 differentiation, likely due to downregulation of TSC1 and DUSP10.

MicroRNA-29b variants and MxA expression change during interferon beta therapy in patients with relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system (CNS) characterized by immune-mediated demyelination and axonal injury. Myelin-reactive IFN-γ-producing Th1 cells has been shown to play an important role in the development of MS. MicroRNAs (miRNAs) are a new class of small non-coding RNA molecules about 22 nucleotides long which regulate gene expression post-transcriptionally by binding to 3' UTR of their mRNA targets, and resulting in degradation or transcriptional repression of the targeted mRNA. Accumulating evidence supports that miRNA dysregulation is linked to the pathogenesis of autoimmune diseases that include MS. miR-29b expression has been shown to be upregulated in memory CD4+T cells from relapsing-remitting MS (RR-MS) patients, which may reflect chronic Th1 inflammation. Interferon beta (IFN-ß) benefits patients with MS and reduces symptoms of the RR-MS. MxA is induced by type I interferon and predicts IFN-ß response in MS patients. The aim of this study was to evaluate miR-29b variants and MxA expression and serum IFN-γ level in responders and non-responders to IFN-ß treatment. METHODS: A total of 70 IFN-ß treated RR-MS patients including 35 responders and 35 non-responders were enrolled. We analyzed the expression level of miR-29b variants and MxA using the peripheral blood of MS patients treated with IFN-ß for more than one year. Real-time RT-PCR was performed to analyze miR-29b variants and MxA expression one year after initiation of IFN-ß therapy. Serum cytokine level was measured by ELISA. RESULTS: The results indicated that the expression level of miR-29b-3p changed related to IFN-ß response. Moreover, miR-29b-5p was downregulated under IFN-ß treatment in responders versus non-responders. MxA level was significantly decreased in the responders. There was no change in IFN-γ level following treatment with IFN-ß in the MS patients. CONCLUSIONS: Our results might provide fundamentals for the development of new markers of the biological effects of IFN-ß therapy.

Hepatic Hemodynamic Changes Following Stepwise Liver Resection.

AIM: Extended liver resection has increased during the last decades. However, hepatic hemodynamic changes after resection and the consequent complications like post hepatectomy liver failure are still a challenging issue. The aim of this study was to systematically evaluate the role of stepwise liver resection on hepatic hemodynamic changes. METHODS: To evaluate this effect we performed 25, 50, and 75 % sequential liver resections in 10 pigs. Before and after each resection, the hepatic artery flow and portal vein flow in relation to the remnant liver volume (RLV) as well as hepatic vascular pressures were measured and compared between the groups. RESULTS: Following sequential liver resection, the hepatic artery flow /100 g decreases and the portal vein flow increases up to 17 and 167 % following extended liver resection (75 %), respectively. Also, during stepwise liver resection, the portal vein pressure increases gradually up to 33 % following extended hepatectomy (75 %). CONCLUSION: Sequential decrease in the RLV decreases the hepatic artery flow /100 g and increases the portal vein flow /100 g and portal vein pressure. As the consequence, the liver goes under more poor-oxygenated blood supply and higher pressure. This may be one of the most important mechanisms of the post hepatectomy liver failure in case of extended liver resection.

Detection of mecA and enterotoxin genes in Staphylococcus aureus isolates associated with bovine mastitis and characterization of Staphylococcal cassette chromosome mec (SCCmec) in MRSA strains.

BACKGROUND AND OBJECTIVES: Staphylococcus aureus is one of the main causatives of bovine mastitis. Resistance of some strains to methicillin, can complicate the treatment of its infections. On the other hand, enterotoxin production is also important. Therefore, the aim of our study was to investigate the methicillin resistance and enterotoxin production in S. aureus isolates caused bovine mastitis. MATERIALS AND METHODS: Four hundred and fifty milk samples were collected. After isolation of Staphylococcus aureus, MRSA strains were detected by cefoxitin disc diffusion and oxacillin agar screening methods. DNA was extracted by phenol - chloroform method and PCR was applied for mecA, sea and seb genes. SCCmec types of mecA gene were identified using multiplex-PCR. RESULTS: Fifty-four (12%) S. aureus were isolated. Out of these, 10 and 9 MRSA strains identified by cefoxitin disc diffusion and oxacillin agar screening methods, respectively. All 10 MRSA isolates identified by cefoxitin disc diffusion, were positive for mecA gene and all of them belonged to SCCmec type IV. The sea genes were detected in 19 isolates and only two isolates were positive for seb genes. One isolate possessed both sea and seb genes. CONCLUSION: Findings of this study indicated that results of cefoxitin disc diffusion test is in concordance with the PCR for mecA gene and has a higher sensitivity compared to oxacillin agar screening method. Finally, Our findings suggest that enterotoxin A is the dominant type.

Long-Term Follow-Up of Kidney Transplant Recipients With Polycystic Kidney Disease.

OBJECTIVES: Patients with polycystic kidney disease are candidates for kidney transplant. We report the results of our single center study of 250 first transplant recipients with polycystic kidney disease (autosomal dominant [64%], medullary cystic [16%], autosomal recessive [6%], and nonspecified [14%]). MATERIALS AND METHODS: Patient groups were divided and analyzed according to the origin of the graft (deceased donor or living donor). We also analyzed demographic data of donors and recipients, waiting time, duration of dialysis, transfusion, nephrectomy, hospitalization, morbidities, and graft and patient survival. The study was approved by the Ethical Review Committee of the Institute. All of the protocols conformed to the ethical guidelines of the 1975 Helsinki Declaration. RESULTS: The deceased-donor group comprised 79% and the living-donor group comprised 21% of the cases. Nephrectomy was performed on 21% of the recipients. The deceased-donor group showed significantly higher values than the living-donor group regarding rate of hemodialysis (82% vs 68%), duration of dialysis (1571 vs 1002 days), waiting time (1129 vs 33 days), and blood transfusions (45% vs 27%). In deceased-donor versus living-donor transplant recipients, surgical complications included arterial stenosis (1% vs 0%), venous thrombosis (1% vs 0%), urine leakage (0.5% vs 1.9%), ureteral stenosis (0.5% vs 0%), reflux (0% vs 1.9%), lymphocele (11.7% vs 8.1%), and hernia (5.2% vs 8.1%), with no statistically significant differences shown between the groups. The living-donor group had graft and patient survival rates as high as the deceased-donor group. CONCLUSIONS: The low rate of morbidity and excellent survival rates make kidney transplant an excellent option for patients with polycystic kidney disease. Although fear of future appearance of polycystic kidney disease may reduce the rate of related living donors, our study showed that graft and patient survival rates in the living-donor group were as high as in the deceased-donor group.

Hope of patient recovery in the ICU from the viewpoint of Iranian nurses: concept analysis.

Nurses' care quality for patients in the ICU depends on their degree/ level of hope to improving patient, but there is no consensus on the concept "hoping to improve patient." The purpose of the present study is to analyze the concept nurses hoping to improving patient in the ICU. To analyze this concept, hybrid model is used which consists of theoretical phase, field work phase, and final analytical phase. In field phase work, semi-structured, face to face and individual interviews were done for nurses working in the ICU, and the data gathered from the interviews were analyzed using inductive content analysis. In theoretical phase, the concept hoping to improve patient was characterized by being available, being professional, expecting positively, and being future- oriented. The scientific definition of this concept was explained through properties which are necessary for qualified nursing care. In field work phase, the categories include nursing care, inner feeling, belief and consequences. In final analytical phase, final definition of the concept was explained through properties such as dynamic expectation, being realistic, and being goal- oriented which is a better function and attitude in effective nursing care accompanying peace of mind for nurses. Concept analysis showed that nurse's awareness of hoping to improve patient helps the nurse do his job in the best way and with peace of mind.