Group 3 innate lymphoid cells regulate neutrophil migration and function in human decidua.

Innate lymphoid cells (ILCs) have a central role in innate defenses against pathogens, lymphoid organogenesis, and tissue remodeling. They have been detected in human decidua, however, their role in this tissue remains unclear. Successful pregnancy requires an early inflammatory phase favoring implantation and tissue remodeling as well as a subsequent regulatory phase to prevent fetal rejection and supporting neoangiogenesis. Here, we show that, during the first trimester of pregnancy, neutrophils infiltrate decidua basalis and are more abundant in normal pregnancy than in spontaneous miscarriages. Decidual neutrophils localize in proximity of NCR+ILC3, which may influence neutrophil migration and survival given their production of CXCL8 and granulocyte macrophage colony-stimulating factor (GM-CSF). Moreover, NCR+ILC3-derived GM-CSF was found to induce the expression of heparin-binding EGF-like growth factor and IL1ra in neutrophils, two proteins/cytokines involved in tissue remodeling and maintenance of pregnancy. Our data suggest that the simultaneous presence of NCR+ILC3 and neutrophils in decidual tissues and their possible cross talk, may have a role in the early phases of pregnancy.

Immunohistochemical study of RhoC GTPase in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a disease with high mortality and morbidity. Metastasis is a significant prognostic factor of the OSCC patients. The Rho GTPases are signaling proteins that controls important cellular processes in various complex mechanisms involved in carcinogenesis. This study aimed to evaluate the expression pattern of RhoC in OSCC protein by immunohistochemistry in situ. Immunohistochemical reactions were performed for RhoC by the method of avitina-biotin-peroxidase activity in samples OSCC: well differentiated (BD, n=6), moderately differentiated (MD, n=24) and poorly differentiated (PD, n=13). The morphometry was taken by QuickScore (percentage and intensity of staining) and only intensity staining. There was no statistical difference (p>0.05) through none of the modes of morphometric analysis between BD, MD and PD. And the RhoC staining was not associated with the histopathologic grading (χ2 = 4.65, p>0.05). However, the morphological evaluation of immunostained for RhoC in cases BD, MD, PD OSCC, regardless of histopathologic grading. These results suggest that there is no correlation between the RhoC immunoexpression and histopathological grading of OSCC.

Rapid reconstitution of functionally active 6-sulfoLacNAc(+) dendritic cells (slanDCs) of donor origin following allogeneic haematopoietic stem cell transplant.

The role of dendritic cells (DCs) and macrophages in allogeneic haematopoietic stem cell transplant (HSCT) is critical in determining the extent of graft-versus-host response. The goal of this study was to analyse slanDCs, a subset of human proinflammatory DCs, in haematopoietic stem cell (HSC) sources, as well as to evaluate their 1-year kinetics of reconstitution, origin and functional capacities in peripheral blood (PB) and bone marrow (BM) of patients who have undergone HSCT, and their presence in graft-versus-host disease (GVHD) tissue specimens. slanDCs were also compared to myeloid (m)DCs, plasmacytoid (p)DCs and monocytes in HSC sources and in patients' PB and BM throughout reconstitution. slanDCs accounted for all HSC sources. In patients' PB and BM, slanDCs were identified from day +21, showing median frequencies comparable to healthy donors, donor origin and kinetics of recovery similar to mDCs, pDCs, and monocytes. Under cyclosporin treatment, slanDCs displayed a normal pattern of maturation, and maintained an efficient chemotactic activity and capacity of releasing tumour necrosis factor (TNF)-α upon lipopolysaccharide (LPS) stimulation. None the less, they were almost undetectable in GVHD tissue specimens, being present only in intestinal acute GVHD samples. slanDCs reconstitute early, being donor-derived and functionally competent. The absence of slanDCs from most of the GVHD-targeted tissue specimens seems to rule out the direct participation of these cells in the majority of the local reactions characterizing GVHD.

[Infective endocarditis in patients with congenital heart disease]. / Endocardite infettiva nei cardiopatici congeniti.

The incidence of infective endocarditis (IE) in patients with congenital heart disease (CHD) is higher than in general population; this is a major problem considering the continuous expansion of such group of patients. Generally the more complex is the congenital heart disease the higher is the risk of IE. The aetiology, clinical features, complications, basis for diagnosis and treatment of IE in CHD patients don't differ from those in acquired cardiac disease; however, right-sided IE is more frequent in CHD patients. Due to the complex anatomy or presence of artificial material in many CHD, the transesophageal echocardiogram is extremely useful although echocardiographic assessment remains difficult. Prognosis is better than in other forms of IE with a mortality rate <10%. Primary prevention is crucial: a good oral-dental hygiene and regular dental review are as important as antibiotic prophylaxis; however this awareness in the CHD population is still not satisfactorily spread due to an educational problem. New IE guidelines from International Cardiology Societies emphasize the role of primary prevention and limit antibiotic prophylaxis to the highest risk patients undergoing the highest risk procedures. This article reviews the main reasons justifying the revision of previous IE guidelines, focuses on criteria to select CHD patients requiring antibiotic prophylaxis and gives information about antibiotic therapy to use.

[Cardiopulmonary exercise test in adults with congenital heart disease]. / Prova cardiopolmonare in pazienti adulti con cardiopatia congenita.

Cardiopulmonary exercise testing (CPET) gives important information about functional capacity by direct measurement of exercise respiratory gas exchange. It provides assessment of the integrative exercise responses involving the cardiovascular, respiratory and muscle-skeletal systems which are not adequately investigated through the measurement of individual organ system function. CPET involves measurements of oxygen uptake (VO2), carbon dioxide production (VCO2) and several ventilatory measures. CPET is increasingly being used as a clinical tool to determine functional capacity, prognosis and potential need for medical or surgical interventions in patients affected by congenital heart disease (CHD). Also in this population, peak VO2 and slope VE/VCO2 are the most predictive parameters in terms of mortality and need of hospitalization. Cyanotic patients with Esisenmenger syndrome show the worst functional limitation and consequently the worst prognosis. This article provides basic and practical information about CPET and focuses on its interpretation in patients with CHD.

[Interventional procedure in the Cath Lab: the state of art]. / L'Emodinamica interventistica.

Many paediatric cardiac patients now survive to adulthood following early surgery. This population of adult patients with a congenital heart disease offer distinct challenges such as unusual anatomy and demands such as pregnancy and exercise tolerability not found in conventional paediatric or traditional adult interventional patients. Starting with neonatal balloon atrial septostomy for transposition of the great arteries, improving and changing percutaneous interventional techniques have increasingly replaced surgery as a treatment option in several congenital heart diseases. There has been a rapid growth in interventional cardiology techniques to treat adults with congenital heart disease, mirroring the rise of interventional cardiology as a cardiology subspecialty and the increasing population of adults with congenital abnormalities. We review current indications for adult congenital heart disease intervention and best practice, reviewing the patient spectrum commonly treated, devices used, and emerging treatments.

Antimycobacterial activity of lichen substances.

We describe here the extraction and identification of several classes of phenolic compounds from the lichens Parmotrema dilatatum (Vain.) Hale, Parmotrema tinctorum (Nyl.) Hale, Pseudoparmelia sphaerospora (Nyl.) Hale and Usnea subcavata (Motyka) and determined their anti-tubercular activity. The depsides (atranorin, diffractaic and lecanoric acids), depsidones (protocetraric, salazinic, hypostictic and norstictic acids), xanthones (lichexanthone and secalonic acid), and usnic acid, as well seven orsellinic acid esters, five salazinic acid 8',9'-O-alkyl derivatives and four lichexanthone derivatives, were evaluated for their activity against Mycobacterium tuberculosis. Diffractaic acid was the most active compound (MIC value 15.6mug/ml, 41.6 microM), followed by norstictic acid (MIC value 62.5 microg/ml, 168 microM) and usnic acid (MIC value 62.5 microg/ml, 182 microM). Hypostictic acid (MIC value 94.0 microg/ml, 251 microM) and protocetraric acid (MIC value 125 microg/ml, 334 microM) showed moderate inhibitory activity. The other compounds showed lower inhibitory activity on the growth of M. tuberculosis, varying from MIC values of 250 to 1370 microM.

Androgenic juvenile granulosa cell tumor of the ovary with cystic presentation: a case report.

Granulosa cell tumors account for approximately 1-2% of all ovarian tumors. There are two types: adult granulosa cell tumor and juvenile granulosa cell tumor. Juvenile granulosa cell tumors constitute 5% of this histological subtype, and the prognosis is good because the majority present as Stage I tumors. The treatment can consist of conservative surgery. Androgen production is rare and produces virilization in women. These tumors are usually solid or predominantly solid. We describe the case of a 13-year-old girl with androgenic manifestations and increased abdominal size. Her plasma testosterone level was elevated. A left adnexal cyst (14.4 x 9.1 x 9.7 cm) was revealed at pelvic ultrasonography. The patient underwent an exploratory laparotomy, revealing a left ovarian cystic tumor. Diagnosis was juvenile granulosa cell tumor.

Role of atrial septostomy in the treatment of children with pulmonary arterial hypertension.

OBJECTIVES: To assess in retrospect the safety and effectiveness of atrial septostomy in children with severe pulmonary arterial hypertension without an intracardiac communication. METHODS: 20 patients were reviewed retrospectively, 19 with idiopathic pulmonary arterial hypertension. The mean age at septostomy was 8.4 years (range 3 months to 17 years). Graded balloon septostomy alone was carried out in eight patients, a blade septostomy was done in two, a blade septostomy plus graded balloon septostomy was done in three, and a fenestrated device was inserted in seven. RESULTS: There were no fatalities. Four children suffered complications during the procedure. None had further syncope and all improved symptomatically with a significant (p < 0.01) decrease in World Health Organization functional class (mean shift -0.6) and a significant improvement in the semiquantitative echocardiographic assessment of right ventricular function (p < 0.03). The mean oxygen saturation decreased by 7.8 percentage points. The atrial communication closed in two children, necessitating a repeat procedure. After a mean follow up of 2.1 years (range one month to 6.7 years), 18 of 20 children are still alive. CONCLUSION: Atrial septostomy improved symptoms and quality of life in a group of children deteriorating with severe pulmonary arterial hypertension. This procedure is to be recommended for severely symptomatic children, before they become critically ill. Fenestrated devices may help ensure indefinite patency of the atrial communication.

Occurrence and risk factors for benign epithelial gastric polyps in atrophic body gastritis on diagnosis and follow-up.

BACKGROUND: Benign epithelial gastric polyps have been reported to be more common in atrophic body gastritis. The role of Helicobacter pylori infection in the induction of gastric atrophy is well-known. The development of hyperplastic polyps may be in relation to H. pylori infection. AIM: To investigate occurrence of benign epithelial gastric polyps in atrophic body gastritis patients at diagnosis and follow-up, and the role of H. pylori and other risk factors for the development of benign epithelial gastric polyps. METHODS: A total of 259 consecutive atrophic body gastritis patients included in a follow-up programme, of whom 202 were followed up for median period of 4 years (range: 2-11). At baseline and follow-up gastroscopies, the presence of benign epithelial gastric polyps was evaluated. Biopsies for histology were obtained from all detected benign epithelial gastric polyps. RESULTS: Frequency of benign epithelial gastric polyps in atrophic body gastritis patients were 4.6% at baseline and 5.9% at follow-up. About 91.7% were hyperplastic polyps. H. pylori infection was detected in 79.2% atrophic body gastritis patients with benign epithelial gastric polyps, and in 70.8% without benign epithelial gastric polyps. Smoking was more frequent among patients with benign epithelial gastric polyps [42% vs. 20%, OR 2.8 (95% CI: 1.2-6.9)]. CONCLUSIONS: Benign epithelial gastric polyps occur in about 5% of atrophic body gastritis patients, and the vast majority are hyperplastic polyps. Smoking habit, but not H. pylori infection, increases the risk for benign epithelial gastric polyps in atrophic body gastritis patients.

Physical exercise intensity can be related to plasma glutathione levels.

The aim of the present study was to examine the effect of different kinds of physical exercise on plasma glutathione levels. Male Wistar rats were randomly divided into four groups: In walking group (W; n=6), rats were trained to walk 0.8 m/min for 45 min; slow running group (SR; n=6) were trained to run 4 m/min for 45 min; fast running group (FR; n=6) ran 8m/min for 60 min and control rats (C; n=6) remained in their home cages. All animals were sacrificed after exercise and the levels of reduced glutathione (GSH) in plasma samples determined by high performance liquid chromatography (HPLC) with a fluorescent detector. Compared to controls, exercise did not change GSH plasma levels of the W group. A tendency to decrease blood GSH was observed in plasma samples of the SR group and in the FR group, physical exercise resulted in a dramatic decrease in GSH plasma levels. These data suggest that during light physical exercise there is a low production of reactive oxygen species (ROS) with a low request for antioxidant defence such as oxidation of GSH. The dramatic decrease observed in GSH levels in FR rats would indicate the presence of oxidative stress able to modify blood antioxidant profiles. Our results suggest that GSH plays a central antioxidant role in blood during intensive physical exercise and that its modifications are closely related to exercise intensity.

Physical exercise intensity can be related to plasma glutathione levels.

The aim of the present study was to examine the effect of different kinds of physical exercise on plasma glutathione levels. Male Wistar rats were randomly divided into four groups: In walking group (W; n=6), rats were trained to walk 0.8 m/min for 45 min; slow running group (SR; n=6) were trained to run 4 m/min for 45 min; fast running group (FR; n=6) ran 8 m/min for 60 min and control rats (C; n=6) remained in their home cages. All animals were sacrificed after exercise and the levels of reduced glutathione (GSH) in plasma samples determined by high performance liquid chromatography (HPLC) with a fluorescent detector. Compared to controls, exercise did not change GSH plasma levels of the W group. A tendency to decrease blood GSH was observed in plasma samples of the SR group and in the FR group, physical exercise resulted in a dramatic decrease in GSH plasma levels. These data suggest that during light physical exercise there is a low production of reactive oxygen species (ROS) with a low request for antioxidant defence such as oxidation of GSH. The dramatic decrease observed in GSH levels in FR rats would indicate the presence of oxidative stress able to modify blood antioxidant profiles. Our results suggest that GSH plays a central antioxidant role in blood during intensive physical exercise and that its modifications are closely related to exercise intensity.

Zinc status in athletes: relation to diet and exercise.

Zinc is involved in the biochemical processes supporting life, such as cellular respiration, DNA reproduction, maintenance of cell membrane integrity and free radical scavenging. Zinc is required for the activity of more than 300 enzymes, covering all 6 classes of enzyme activity. Zinc binding sites in proteins are often of distorted tetrahedral or trigonal bipyramidal geometry, made up of the sulphur of cysteine, the nitrogen of histidine or the oxygen of aspartate and glutamate, or a combination. Zinc in proteins can either participate directly in chemical catalysis or be important for maintaining protein structure and stability. The nutritional habits of elite athletes during training and competition are quite different from the recommended diet in the majority of the population. Endurance athletes often adopt an unusual diet in an attempt to enhance performance: an excessive increase in carbohydrates and low intake of proteins and fat may lead to suboptimal zinc intake in 90% of athletes. Mild zinc deficiency is difficult to detect because of the lack of definitive indicators of zinc status. In athletes, zinc deficiency can lead to anorexia, significant loss in bodyweight, latent fatigue with decreased endurance and a risk of osteoporosis.

CD40 ligation ablates the tolerogenic potential of lymphoid dendritic cells.

The outcome of dendritic cell (DC) presentation of P815AB, a tolerogenic tumor/self peptide, depends on a balance between the respective immunogenic and tolerogenic properties of myeloid (CD8 alpha(-)) and lymphoid (CD8 alpha(+)) DC. We have previously shown that CD8(-) DC can be primed by IL-12 to overcome inhibition by the CD8(+) subset and initiate immunogenic presentation in vivo when the two types of peptide-pulsed DC are cotransferred into recipient hosts. IFN-gamma enhances the inhibitory activity of CD8(+) DC on Ag presentation by the other subset, blocking the ability of IL-12-treated CD8(-) DC to overcome suppression. We report here that CD40 ligation on lymphoid DC ablated their inhibitory function on Ag presentation as well as IFN-gamma potentiation of the effect. CD40 modulation of IFN-gamma action on lymphoid DC involved a reduction in IFN-gamma R expression and tryptophan-degrading ability. This effect was accompanied in vitro by an impaired capacity of the CD40-modulated and IFN-gamma-treated DC to initiate T cell apoptosis. In vivo, not only did CD40 triggering on lymphoid DC abrogate their tolerogenic activity, but it also induced the potential for immunogenic presentation of P815AB. Importantly, a pattern similar to P815AB as well as CD40 modulation of lymphoid DC function were observed on testing reactivity to NRP, a synthetic peptide mimotope recognized by diabetogenic CD8(+) T cells in nonobese diabetic mice.

N-acetylcysteine increases apoptosis induced by H(2)O(2) and mo-antiFas triggering in a 3DO hybridoma cell line.

N-Acetylcysteine (NAC) has been used as an antioxidant to prevent apoptosis triggered by different stimuli in different cell types. It is common opinion that cellular redox, which is largely determined by the ratio of oxidized and reduced glutathione (GSH), plays a significant role in the propensity of cells to undergo apoptosis. However, there are also contrasting opinions stating that intracellular GSH depletion or supplemented GSH alone are not sufficient to lead cells to apoptosis or conversely protect them. Unexpectedly, this study shows that NAC, even if it maintains the peculiar characteristics of an agent capable of reducing cell proliferation and increasing intracellular GSH content, increases apoptosis induced by H(2)O(2) treatment and mo-antiFas triggering in a 3DO cell line. We found that 24 h of NAC pre-treatment can shift cellular death from necrotic to apoptotic and determine an early expression of FasL in a 3DO cell line treated with H(2)O(2).

Stereological analysis and modelling of gradient structures

Gradient structures are inhomogeneous along a particular gradient direction but homogeneous perpendicular to that direction. Consequently, structural parameters such as volume fraction or surface area density are local characteristics which depend on the 'vertical' coordinate with respect to the 'vertical' gradient axis. Analogously, models for gradient structures have model parameters depending on the vertical coordinate z. For example, a Voronoi tessellation with a gradient is generated by a gradient point process with a local intensity which is a function of z. Similarly, a gradient germ grain model is obtained from a gradient point process where the grain size distribution may also depend on z. For a gradient Boolean model, local volume fraction VV(z) and local surface area density SV(z) can be calculated from the model parameters. Stereological methods for gradient structures are based on vertical sections parallel to the gradient direction. Estimation of VV(z), SV(z) and local length density LV(z) is done by lineal analysis using horizontal test lines with vertical coordinate z. Similarly, lineal analysis is used to estimate local mean cell volume of gradient tessellations. For the estimation of local particle number density and size in the spirit of the Wicksell problem the use of kernel methods and distributional assumptions is required.

[Endoscopic palliative treatment of a neoplastic esophageal fistula: report of a case]. / Palliazione endoscopica di una fistola neoplastica esofagea: caso clinico.

Oesophago-respiratory neoplastic fistulas present serious problems of management, because of the severe status of the patient. Therefore, a palliative treatment, to allow for a gradual respiratory and digestive function recovery with clinical improvements is needed. Surgical palliation has a mortality rate of 40% and a long post-operative hospitalization. Endoscopic palliation, on the other hand, has the same percentage of success of surgical palliation, but has the advantage to be performed in those patients with severe health conditions immediately improving the symptomatology and not excluding a subsequent surgical approach. The Authors present the case of a 70-year-old patient with a neoplastic relapse on the oesophago-gastric anastomosis, associated to an oesophago-respiratory fistula manifesting as severe dysphagia and dyspnoea. An endoscopic palliative treatment of the fistula was performed introducing a metallic coated prosthesis into the oesophagus. Severe clinical conditions regressed immediately and after 3 months they are unchanged. The Authors suggest endoscopic palliation with oesophageal prosthesis as the best therapeutic choice in those cases not amenable to surgery.

High-performance liquid chromatographic determination of orotic acid as its methyl derivative in human urine.

Described is a method for the determination of orotic acid as its methyl ester in human urine. The method involves the use of solid-phase extraction to isolate pyrimidines from urine and derivatization with methanol and sulfuric acid, followed by isocratic high-performance liquid chromatography on a reversed-phase C18 column with UV absorbance detection. The assay is shown to be sufficiently sensitive for use in clinical investigations where elevated orotic acid excretion is suspected.