Impact of intestinal mannitol on hyperammonemia,oxidative stress and severity of hepatic encephalopathy in the ED

Hyperammonemia results from hepatic inability to remove nitrogenous products generated by protein metabolism of intestinal microbiota, which leads to hepatic encephalopathy (HE) in chronic liver disease (CLD). In ammonium neurotoxicity, oxidative stress (OxS) plays a pathogenic role. Our objective was to evaluate if intestinal mannitol is as effective and safe as conventional treatment for diminishing hyperammonemia, OxS, and HE in patients with CLD.

Total fluid intake of children and adolescents: cross-sectional surveys in 13 countries worldwide

Purpose

To describe total fluid intake (TFI) according to socio-demographic characteristics in children and adolescents worldwide.

Methods

Data of 3611 children (4–9 years) and 8109 adolescents (10–18 years) were retrieved from 13 cross-sectional surveys (47 % males). In three countries, school classes were randomly recruited with stratified cluster sampling design. In the other countries, participants were randomly recruited based on a quota method. TFI (drinking water and beverages of all kinds) was obtained with a fluid-specific record over 7 consecutive days. Adequacy was assessed by comparing TFI to 80 % of adequate intake (AI) for total water intake set by European Food Safety Authority. Data on height, weight and socio-economic level were collected in most countries.

Results

The mean (SD) TFI ranged from [1.32 (0.68)] to [1.35 (0.71)] L/day. Non-adherence to AIs for fluids ranged from 10 % (Uruguay) to >90 % (Belgium). Females were more likely to meet the AIs for fluids than males (4–9 years: 28 %, OR 0.72, p = 0.002; 10–18 years: 20 %, OR 0.80, p = 0.001), while adolescents were less likely to meet the AI than children (OR 1.645, p < 0.001 in males and OR 1.625, p < 0.001 in females).

Conclusions

A high proportion of children and adolescents are at risk of an inadequate fluid intake. This risk is especially high in males and adolescents when compared with females or children categories. This highlights water intake among young populations as an issue of global concern.

     

Ventilation/perfusion (V/Q) scanning in contemporary patients with pulmonary embolism: utilization rates and predictors of use in a multinational study

Journal of Thrombosis and Thrombolysis - Ventilation/perfusion (V/Q) imaging and computed tomography pulmonary angiography (CTPA) are common tools for acute pulmonary embolism (PE) diagnosis....     

Circulating monoclonal immunoglobulins in Sjögren syndrome: prevalence and clinical significance in 237 patients

We conducted the current study to analyze the prevalence and clinical significance of circulating monoclonal immunoglobulins in patients with Sj?gren syndrome (SS), focusing on the association with extraglandular features, immunologic markers, hematologic neoplasia, and hepatitis C virus (HCV) infection. We performed serum immunoelectrophoresis in 200 patients with primary SS and 37 patients with HCV-related SS. All patients fulfilled 4 or more of the 1993 European classification criteria for SS.Of the 200 patients with primary SS, 35 (18%) presented circulating monoclonal immunoglobulins. The monoclonal bands identified were 20 IgG (13 kappa, 7 lambda), 10 IgM (5 kappa, 5 lambda), 2 IgAkappa, and 3 free circulating light chains. Of the 37 SS-HCV patients, 16 (43%) had circulating monoclonal immunoglobulins. The monoclonal bands identified were 10 IgMkappa, 5 IgGlambda, and 1 free light lambda chain. Compared with primary SS patients, SS-HCV patients presented a higher frequency of monoclonal immunoglobulins (43% vs 18%, p = 0.001), with monoclonal IgMkappa being the most frequent monoclonal band. Six (12%) of the 51 SS patients with circulating monoclonal immunoglobulins presented hematologic neoplasia, compared with 3 (1.6%) of those without monoclonal immunoglobulins (p = 0.004; odds ratio = 8.13; 95% confidence intervals, 1.64-51.54). In 2 of the 6 patients with monoclonal immunoglobulins and lymphoproliferative disorders, a change of the monoclonal component was detected in previous immunoelectrophoresis determinations before the development of hematologic neoplasia. Circulating monoclonal immunoglobulins were detected in nearly 20% of patients with primary SS, with monoclonal IgG being the most frequent type of immunoglobulin detected. In SS-HCV patients, the prevalence of monoclonal immunoglobulins was higher (43%), with monoclonal IgM being the most frequent type found. SS-HCV patients presented a more restrictive monoclonal expression (limited to either monoclonal IgMkappa or monoclonal IgGlambda) than primary SS patients, who showed all types of heavy and light chains.     

Influence of the degree of adherence to the mediterranean diet and its components on cardiometabolic risk during pregnancy. The GESTAFIT project

Background and aimsStudies regarding dietary patterns and cardiometabolic risk markers during pregnancy are scarce. The aim of the present study was to analyse whether different degrees of adherence to the Mediterranean diet (MD) and the MD components were associated with cardiometabolic markers and a clustered cardiometabolic risk during pregnancy.Methods and resultsThis study comprised 119 pregnant women from the GEStation and FITness (GESTAFIT) project. Dietary habits were assessed with a food frequency questionnaire at the 16th and 34th gestational weeks (g.w.). The Mediterranean Diet Score was employed to assess MD adherence. The following cardiometabolic markers were assessed: pre-pregnancy body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, triglycerides and high-density lipoprotein cholesterol (HDL-C). A greater MD adherence was associated with a better cardiometabolic status in cross-sectional (16th g.w. and 34th g.w.) and prospective analyses (MD adherence at the 16th g.w. and cardiometabolic markers at the 34th g.w.; SBP, DBP and HDL-C; all, p < 0.05). Participants with the highest MD adherence (Tertile 3) had a lower clustered cardiometabolic risk than those with the lowest MD adherence (Tertile 1) at the 16th and 34th g.w. (both, p < 0.05). A higher intake of fruits, vegetables and fish and a lower intake of refined cereals and red meat and subproducts were associated with a lower cardiometabolic risk during pregnancy (all, p < 0.05).ConclusionA higher MD adherence, a greater intake of fruits, vegetables and fish and a lower intake of refined cereals and red meat and subproducts showed a cardioprotective effect throughout gestation.     

Preventive effect of zaprinast and 3-isobutyl, 1-methylxanthine (phosphodiesterase inhibitors) on gastric injury induced by nonsteroidal antiinflammatory drugs in rats

Cyclic GMP plays an important role in maintaining homeostasis in the gastric mucosa. NSAIDs damage the mucosa by mechanisms that may be mediated by alterations in the intragastric concentration of cyclic GMP. To test this hypothesis we studied the effects of the oral administration of acetylsalicylic acid (100, 300, and 500 mg/kg), piroxicam (5, 10, and 20 mg/kg) and sodium diclofenac (10, 25, 50, and 100 mg/kg), and of their interaction with zaprinast (5 mg/kg) and IBMX (10 mg/kg), on intragastric concentrations of cyclic GMP and the gastric erosive index in rats. All determinations were done 3 hr after the NSAID was given. All NSAIDs induced dose-dependent decreases in mucosal concentrations of cyclic GMP, which correlated inversely with the surface area showing mucosal injury. In contrast, cyclic GMP concentrations remained normal, and no intragastric damage was seen in rats given zaprinast (cyclic GMP-specific phosphodiesterase inhibitor) or IBMX (non-specific phosphodiesterase inhibitor) or in combination with NSAIDs. These findings are in line with the hypothesis that cyclic GMP is involved in the biochemical mechanisms of NSAID-induced gastric injury.     

Folic acid deficiency and neutrophil dysfunction

Polymorphonuclear leukocyte functions were studied in 92 patients with protein-calorie malnutrition. Serum folic acid levels were higher than 3 ng/ml in 38 patients and 3 ng/ml or less in 54 patients. Significant differences were found between these two groups of patients with regard to phagocytosis (81.5 +/- 1.9 versus 69.2 +/- 2.0 percent, p less than 0.001) and bactericidal ability (90.6 +/- 1.1 versus 84.5 +/- 2.3 percent, p less than 0.05). Correction of folic acid deficiency in 22 patients was associated with recovery of normal phagocytosis (p less than 0.001) but not bactericidal function. Adding folic acid to the serum of eight patients also restored normal phagocytic function (p less than 0.001). A correlation was found in vivo and in vitro between changes over time in folic acid levels and in phagocytosis.     

MT1-MMP collagenolytic activity is regulated through association with tetraspanin CD151 in primary endothelial cells

MT1-MMP plays a key role in endothelial function, as underscored by the angiogenic defects found in MT1-MMP deficient mice. We have studied the molecular interactions that underlie the functional regulation of MT1-MMP. At lateral endothelial cell junctions, MT1-MMP colocalizes with tetraspanin CD151 (Tspan 24) and its associated partner alpha3beta1 integrin. Biochemical and FRET analyses show that MT1-MMP, through its hemopexin domain, associates tightly with CD151, thus forming alpha3beta1 integrin/CD151/MT1-MMP ternary complexes. siRNA knockdown of HUVEC CD151 expression enhanced MT1-MMP-mediated activation of MMP2, and the same activation was seen in ex vivo lung endothelial cells isolated from CD151-deficient mice. However, analysis of collagen degradation in these experimental models revealed a diminished MT1-MMP enzymatic activity in confined areas around the cell periphery. CD151 knockdown affected both MT1-MMP subcellular localization and its inclusion into detergent-resistant membrane domains, and prevented biochemical association of the metalloproteinase with the integrin alpha3beta1. These data provide evidence for a novel regulatory role of tetraspanin microdomains on the collagenolytic activity of MT1-MMP and indicate that CD151 is a key regulator of MT1-MMP in endothelial homeostasis.     

HIV-associated lymphoma successfully treated with peripheral blood stem cell transplantation

OBJECTIVE: To evaluate feasibility, safety, and efficacy of peripheral blood stem cell collection (PBSCC) and autologous stem cell transplantation (ASCT), to treat patients diagnosed of high-risk or relapsed HIV-associated lymphoma (HIV+ Ly), responding to highly active antiretroviral therapy (HAART). METHODS: Prospective and multicentric study in patients with high-risk or relapsed chemosensitive HIV+ Ly, candidate for consolidation with ASCT. Eligibility criteria were similar to those of HIV- lymphoma. HAART was aimed to be maintained during the procedure. RESULTS: Fourteen patients were admitted. Adequate PBSCC was obtained from all patients (median CD34+ cells was 4.7 x 10(6)/kg). Three patients died before ASCT; two had disease progression and one died from VHC-liver failure. Eleven transplanted patients showed neutrophil engraftment after a median time of 16 days (range, 9-33 days), and nine patients showed platelet engraftment after a median time of 20 days (range, 11-36 days). CD4+ cell counts and HIV viral load (VL) were appropriately preserved along the procedure. No patients died from treatment-related complications. One patient died from lymphoma progression (day +19), and another died in complete remission (CR) with undetectable VL, 15 months after transplant, due to infection. One patient relapsed at 32 months after ASCT. The remaining eight patients are alive in CR with an event-free survival of 65% and a median follow-up of 30 months after ASCT (range, 7-36 months). CONCLUSIONS: These results show that feasibility, safety, and efficacy of PBSCC and ASCT in HIV+ Ly patients responding to HAART are similar to those observed in the HIV- lymphoma setting.