Deficient phospholipase C activity in blood polimorphonuclear neutrophils from patients with liver cirrhosis

BACKGROUND/AIMS: Circulating neutrophils from cirrhotic patients have a reduced capacity to generate superoxide anion (O(2)(-)), which might contribute to frequent bacterial infections in these patients. We studied the signal transduction pathways involved in the generation of O(2)(-) in neutrophils from 98 cirrhotic patients and 46 healthy controls. METHODS: We measured O(2)(-) production in neutrophils induced by fMLP, opsonized zymosan, TNF alpha, NaF, AlF(4)(-), A23187 and phorbol myristate acetate. Furthermore, we measured phospholipase C activity in neutrophils from healthy controls and end-stage cirrhotic patients. RESULTS: O(2)(-) production was decreased in neutrophils from patients in response to fMLP, opsonized zymosan and TNF alpha. Likewise, response of these cells to G-protein stimulation by fluorides was also decreased. These reduced responses correlated significantly with the degree of liver dysfunction. On the contrary, neutrophils from patients responded normally to A23187 and phorbol esters stimulation indicating that Ca(2+)- and PKC-dependent pathways are intact in these cells. Finally, phospholipase C activity was markedly reduced in neutrophils from end-stage liver cirrhosis. CONCLUSIONS: These data confirm that O(2)(-) generation by neutrophils is decreased in patients with cirrhosis, particularly in those with more severe liver dysfunction, and suggest that this defect involves phosphatidylinositol specific phospholipase C activity.     

The proinflammatory mediator CD40 ligand is increased in the metabolic syndrome and modulated by adiponectin

OBJECTIVES: We hypothesized that the CD40/CD40 ligand (CD40L) system is up-regulated in the metabolic syndrome (MS) and modulated by adiponectin (AN). The objectives were: 1) to compare plasma and monocyte CD40L in patients with MS and controls and its association with clinical and biochemical parameters, 2) to investigate platelets as a source of soluble CD40L (sCD40L), and 3) to analyze the effects of AN on CD40/CD40L. METHODS: Plasma sCD40L and AN were measured in 246 controls and 128 patients with MS by ELISA. Monocyte CD40/CD40L expression and platelet CD40L content and release were compared in patients with MS and controls. Monocytes and endothelial cells were cultured with AN and CD40/CD40L expression determined by real-time RT-PCR and Western blotting. RESULTS: Patients with MS had higher sCD40L and lower AN levels than controls (0.89 +/- 0.1 vs. 0.76 +/- 0.07 ng/ml and 10.10 +/- 0.65 vs. 12.99 +/- 0.80 microg /ml, P < 0.05). Monocyte CD40/CD40L expression was higher (P < 0.05) in patients than controls (CD40: 1.31 +/- 0.31 vs. 0.80 +/- 0.14 arbitrary units; CD40L: 1.24 +/- 0.85 vs. 0.43 +/- 0.14 pg/microg protein). No differences were observed on CD40L content between resting platelets from patients with MS and controls (7.7 +/- 3.5 vs. 7.2 +/- 2.2 pg/microg protein). Stimulated platelets from patients with the MS released more (P < 0.05) sCD40L than controls (582 +/- 141 vs. 334 +/- 60% change vs. nonstimulated platelets). AN reduced CD40L mRNA and protein expression in monocytes from MS patients and endothelial cells. CONCLUSIONS: The enhanced sCD40L and cellular CD40L expression in the MS suggests that CD40L is of pathophysiological relevance in MS. Also, a new antiinflammatory effect of AN is described through the modulation of the CD40/CD40L system.     

Latex allergy in healthcare workers: an epidemiological study in a Spanish hospital.

To design an effective prevention program in health care workers who are allergic to latex it is necessary to know the current epidemiological situation. The objectives were to determine the main factors associated with latex allergy and to quantify levels of airborne latex particles in different areas of our hospital. A cross-sectional study was conducted using a questionnaire completed by health care workers. Those who answered the first questionnaire were given a second one to fill out and an allergological study (skin-prick test and latex-specific IgE antibodies) was performed. Latex aeroallergen particles were collected with a Quan-tec-air in different areas of the hospital. The first questionnaire was sent to 2551 health care workers. Eight hundred forty-one (33.14%) subjects returned the completed questionnaire and were given the second questionnaire. One hundred fifty-four completed second questionnaire. We identified 28 patients who were allergic to latex, and 126 patients who were not allergic to latex. In the allergic population there were more nurses aides. More allergic patients were found in the Surgery Department, Intensive Care Unit (ICU), and Vascular Radiology Unit (VRU). Allergic patients were more likely to use a higher number of latex gloves and during more hours than nonallergic workers. In the Surgery Department, ICU, VRU, and Laboratory Department more pairs of latex gloves were used and during more hours. The medium level of latex aeroallergens in 24 determinations in 14 areas of the hospital was 8.12 ng/m3 (SD, 13.32 ng/m3; range, 0.3-57.7 ng/m3). The higher levels were found in Laboratory (n = 2; mean (M) 23; SD, 25.95 ng/m3) and Surgery Departments (n = 11; M, 7.43; SD, 16.98 ng/m3; Kruskal Wallis test, p = 0.09). Latex allergy is an important health problem for health care workers, especially for those working in surgical areas or in those places where more latex gloves are used; in these areas higher levels of airborne latex particles are found. We should take into account these data to design an effective secondary prevention program.     

Systemic lupus erythematosus and Crohn's disease: a case report

A 24-year-old woman with systemic lupus erythematosus (SLE) presented abdominal pain and diarrhea. No evidence for an SLE flare was obtained. Colonoscopy and microscopic biopsy examination revealed findings typical of Crohn's disease. Despite the rarity of the combination, patients with SLE showing gastrointestinal manifestations might merit evaluation for Crohn disease.     

Change in Levels of C-Reactive Protein (CRP) and Serum Cortisol in Morbidly Obese Patients After Laparoscopic Sleeve Gastrectomy

Background

C-Reactive protein (CRP) has been associated with the macro- and microvascular effects of hypertension and diabetes mellitus. Referring to serum cortisol, it has been proposed to contribute to the pathogenesis of metabolic syndrome, and it has been demonstrated that weight loss normalizes cortisol levels and improves insulin resistance. The aims of this study were to analyze CRP and cortisol levels pre- and postoperatively in morbidly obese patients undergoing a laparoscopic sleeve gastrectomy and to correlate them with weight loss and parameters associated with cardiovascular risk.

Methods

A prospective study of all the morbidly obese patients undergoing laparoscopic sleeve gastrectomy as bariatric procedure between October 2007 and May 2011 was performed.

Results

A total of 40 patients were included in the study. CRP levels decreased significantly 12 months after surgery (median reduction of 8.9 mg/l; p?=?0.001). Serum cortisol levels decreased significantly 6 months after surgery (median reduction of 34.9 μg/dl; p?=?0.001). CRP values reached the normal range (<5 mg/l) 1 year after surgery. Referring to cortisol, a significant association was observed with the cardiovascular risk predictor (triglyceride/high-density lipoprotein cholesterol ratio) from the 6th month after surgery onward (Pearson correlation coefficient, 0.559; p?=?0.008).

Conclusion

CRP levels are increased preoperatively and in the postoperative course up to 1 year after surgery. Serum cortisol levels remain elevated until the 6th month after surgery. From this moment onward, serum cortisol is associated with the cardiovascular risk predictor reflecting the cardiovascular risk decreasement during the weight loss.     

Syncytin-1/HERV-W envelope is an early activation marker of leukocytes and is upregulated in multiple sclerosis patients

Syncytin-1 is the envelope protein of the human endogenous retrovirus W (HERV-W). It has been related to multiple sclerosis (MS) but its role in cellular immunity and its pathogenic mechanism in the autoimmune context are not fully understood. We analyzed syncytin-1 levels in peripheral blood mononuclear cells (PBMC) subsets from healthy donors, MS patients in relapse or remission, and patients with acute infections by flow cytometry. PBMC cultures were also prepared to analyze protein expression kinetics. MS patients had higher levels of syncytin-1 levels than controls. We found that syncytin-1 is elevated in monocytes during MS relapses and infections. Cells expressing syncytin-1, including monocytes, T and B lymphocytes, and NKs presented mainly an activated phenotype and, upon stimulation with LPS, its levels increased rapidly on antigen-presenting cells. Syncytin-1 ligation promoted the activation of monocytes, as demonstrated by the upregulation of CD80 and the nonclassical subset CD14^low CD16⁺. Our results suggest an important role for syncytin-1 in the activation of leukocytes. Given that the expression of syncytin-1 is upregulated in MS patients, this protein might be contributing to the autoimmune cascade in the disease.