Immune cells from patients with psoriasis are defective in inducing indoleamine 2,3-dioxygenase expression in response to inflammatory stimuli.

BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) is an inducible enzyme that suppresses the immune response. The role of IDO as a negative regulator of inflammatory responses has been documented in several experimental autoimmune diseases. OBJECTIVES: To explore the regulation of IDO by immune cells in psoriasis and its relation with disease severity. METHODS: The expression and activity of IDO were assessed by reverse-transcriptase polymerase chain reaction, flow cytometry and high-performance liquid chromatography in peripheral blood of patients with moderate-to-severe plaque-type psoriasis. The ability of immune cells to express IDO in response to inflammatory stimuli was studied. The functional role of IDO expression was evaluated in a regulatory T cell (Treg) differentiation assay, using cocultures of immature monocyte-derived dendritic cells with autologous peripheral CD4+ T cells. RESULTS: Analysis of the kynurenine-to-tryptophan ratio in serum samples indicated higher IDO activity in patients with psoriasis than in healthy controls. However, correlation studies showed lower IDO activity in those patients with higher Psoriasis Area and Severity Index (PASI). Although myeloid dendritic cells from patients with psoriasis expressed higher levels of IDO than those from healthy controls, these cells did not upregulate IDO in response to a combination of tumour necrosis factor-α, interleukin (IL)-1ß and IL-6 cytokines. The defective expression of IDO correlated with PASI. Immature monocyte-derived dendritic cells from patients with psoriasis also expressed low levels of IDO and induced CD4+ Treg differentiation poorly. CONCLUSIONS: Immune cells from patients with psoriasis have a defect in upregulating IDO in response to inflammation associated with the severity of psoriasis.

Fraxinus pollen and allergen concentrations in Ourense (South-western Europe).

In temperate zones of North-Central Europe the sensitization to ash pollen is a recognized problem, also extended to the Northern areas of the Mediterranean basin. Some observations in Switzerland suggest that ash pollen season could be as important as birch pollen period. The allergenic significance of this pollen has been poorly studied in Southern Europe as the amounts of ash pollen are low. Due to the high degree of family relationship with the olive pollen major allergen (backed by a sequence identity of 88%), the Fraxinus pollen could be a significant cause of early respiratory allergy in sensitized people to olive pollen as consequence of cross-reactivity processes. Ash tree flowers in the Northwestern Spain during the winter months. The atmospheric presence of Ole e 1-like proteins (which could be related with the Fra a 1 presence) can be accurately detected using Ole e 1 antibodies. The correlation analysis showed high Spearman correlation coefficients between pollen content and rainfall (R(2)=-0.333, p<0.01) or allergen concentration and maximum temperature (R(2)=-0.271, p<0.01). In addiction CCA analysis showed not significant differences (p<0.05) between the component 1 and 2 variables. PCFA analysis plots showed that the allergen concentrations are related to the presence of the Fraxinus pollen in the air, facilitating the wind speed its submicronic allergen proteins dispersion. In order to forecast the Fraxinus allergy risk periods, two regression equations were developed with Adjusted R(2) values around 0.48-0.49. The t-test for dependent samples shows no significant differences between the observed data and the estimated by the equations. The combination of the airborne pollen content and the allergen quantification must be assessed in the epidemiologic study of allergic respiratory diseases.

Reduced expression of galectin-1 and galectin-9 by leucocytes in asthma patients.

Accumulating evidence shows that galectins play roles in the initiation and resolution phases of inflammatory responses by promoting anti- or proinflammatory effects. This study investigated the presence of three members of the galectin family (galectin-1, -3 and -9) in induced sputum samples of asthma patients, as well as their possible implication in the immunopathogenesis of human asthma. Levels of interleukin (IL)-5, IL-13, and galectins were determined in leucocytes isolated from induced sputum samples by reverse transcription-polymerase chain reaction (RT-PCR) immunofluorescence and flow cytometry. High levels of IL-5 and IL-13 mRNA were detected in sputum cells from asthma patients. In parallel, immunoregulatory proteins galectin-1 and galectin-9 showed a reduced expression on macrophages from sputum samples compared with cells from healthy donors. In-vitro immunoassays showed that galectin-1 and galectin-9, but not galectin-3, are able to induce the production of IL-10 by peripheral blood mononuclear cells from healthy donors. These findings indicate that macrophages from sputum samples of asthma patients express low levels of galectin-1 and galectin-9, favouring the exacerbated immune response observed in this disease.

[Jejunal mucormycosis in a patient with Hodgkin's lymphoma]. / Mucormicosis yeyunal en paciente con linfoma de Hodgkin.

We report a case of intestinal mucormycosis in a 46-year-old male diagnosed with classical Hodgkin's disease, IV-B stage. During the first phase of chemotherapy he had a massive digestive bleeding event secondary to a jejunal ulcer, and zygomicosis mucor-type was diagnosed by endoscopic biopsy. The patient was treated with antifungal drugs and surgical resection of the intestine involved. At surgery a double covered perforation of the jejunum was seen. Pathological examination confirmed the previous diagnosis. After one year of follow-up the patient is doing well, and his lymphoma is on remission. To our best knowledge this is the second case of intestinal mucormycosis in a patient with Hodgkin's lymphoma reported in the medical literature.

Oleaceae cross-reactions as potential pollinosis cause in urban areas.

It is worth noting the allergological problems induced by a not accurate design of the ornamental vegetation in the parks and streets of the cities. Usually, in the Oleaceae family, only the olive pollen is considered an important aeroallergen but other species of the family could be an important source of airborne pollen allergens. Pollen from Fraxinus, Olea and Ligustrum and its main aeroallergens were sampled in the atmosphere of an urban area in North-Western Spain during 2011. The allergen bioaerosol content was quantified by using specific 2-site ELISA and Ole e 1 antibodies. The Fra e 1 and Lig v 1 allergens were detected by means Ole e 1 antibodies. This fact demonstrates the cross-reactivity between the main allergens of Fraxinus, Olea and Ligustrum, plants widely species used as ornamental in the cities. Therefore, the urban allergenic people sensitized to Olea pollen could present allergenic reactions during the winter (due to ash pollen allergens), the spring (caused by olive pollen allergens) and the early summer (triggered by the privet flowering). As a consequence, sensitivity to the pollen of one species may favour development of sensitivity to all three species as consequence of the priming effect. The combination of pollen count and the allergen quantification must be assessed in the epidemiologic study of allergic respiratory diseases.

Modification of Le Bag ileocolonic pouch with improved results. Review of 17 cases.

The use of detubularized terminal ileum and cecum to construct a highly compliant, low-pressure, continent ileocolonic pouch was first described by Light and Engelman and was termed the "Le Bag." Results were excellent in terms of continence and preservation of renal function; however, nocturnal incontinence persisted in a substantial number of patients. We have modified the original procedure in 17 patients by performing a urethral-cecal anastomosis instead of using a tail of nondetubularized ileum. In addition, in those patients in whom a urethral anastomosis is contraindicated, we have modified the nipple as the continence-providing mechanism. Overall daytime and nighttime continence rate is 94 percent. Of the 13 patients with urethral-cecal anastomoses, only 1 patient requires intermittent catheterization. The remainder are voiding by Valsalva maneuver and with minimal residual urine. Based on our experience with the Le Bag ileocolonic pouch, we believe it is an excellent choice for total bladder replacement or continent diversion--the advantages being the relative ease of construction, minimal long-term complications, and near total urinary continence.

Shiga toxin 1: damage to DNA in vitro.

Shiga toxins share with plant ribosome-inactivating proteins the same enzymatic mechanism of action: the removal of a specific adenine from 28S RNA when acting on ribosomes and the removal of multiple adenines when acting on DNA in vitro. The activity on DNA, only recently reported, is particularly evident, and has been studied mostly at acidic pH. For the in vitro activity, on both ribosomes and DNA, Shiga toxins require activation by trypsin, urea and dithiothreitol which release the enzymatically active A(1) fragment. Activation by the classical procedure leaves large amounts of urea and DTT which interfere in the DNA depurination assay and completely abolish depurination at physiological pH. A consistent release of [3H]adenine from DNA at neutral pH is instead observed when the toxin is activated in vitro by an improved method which removes most of the drastic reagents required for proteolytic cleavage and reduction. Damage to single-stranded DNA by Shiga toxin 1 (Stx1) primarily involves depurination. A spontaneous DNA breakdown appears in fact only after extensive base removal, a behavior similar to that observed with uracil-DNA glycosylase, a simple glycosylase devoid of lyase activity. NaCl inhibits the activity of Stx1, probably by minimizing the sliding distance traveled by the enzyme along DNA in search of its target sites and promoting dissociation of the substrate-enzyme complex.

[Angiocentric immunoproliferative lesions: the terminology and the clinical picture]. / Lesiones angiocéntricas inmunoproliferativas: terminología y cuadros clínicos.

Two diagnosed clinical cases of T-cell angiocentric lymphoma are presented, different in their clinical aspects, evolution and treatment. Both represent different spectrums within the entity of angiocentric immunoproliferative lesions. The medical literature is reviewed and emphasis is placed on the different illness which include a wide range from less to more highly malignant within the same entity.

[Nocardiosis in 2 immunocompetent patients]. / Nocardiosis en dos pacientes inmunocompetentes.

Two diagnosed clinical cases of nocardiosis in immunocompetent patients are presented, different in their clinical aspects, evolution and treatment. We report a 55 years-old man with disseminated nocardiosis and a 32 years-old man with splenectomy diagnosed of pulmonary nocardiosis. The medical literature is reviewed and emphasis is placed on the different illness and treatment of the nocardiosis.

[Profhylaxis and treatment of hereditary and acquired angioedema at HUB; use of the C1-esterase inhibitor]. / Profilaxis y tratamiento del angioedema hereditario y adquirido en el HUB; utilización del inhibidor de la C1-esterasa.

INTRODUCTION: Hereditary and acquired angioedema result from a deficiency in first complement component esterase (C1-esterase) inhibitor. It is characterized by transient subcutaneous tissue, intestinal wall, and upper airway swelling, which may lead to asphyxia and death. The pathophysiology, classification, diagnosis, and treatment of this condition are discussed, as is the follow-up of patients diagnosed with angioedema who received 1 vial of concentrated C1-INH (Berinert); the contribution of the Pharmacy Department in the dispensation and control of said drug is also assessed. MATERIAL AND METHODS: PubMed and other relevant sources were searched. Patient, dispensation, and Berinert(R) indication data were collected from controlled prescriptions; follow-up was completed by performing a medical history, collecting laboratory data, and patient interview when needed. RESULTS: Eight out of 9 cases were of hereditary angioedema, and 1 case was of acquired angioedema. Danazol was used as long-term prophylaxis in 8 patients, but side effects forced discontinuation in some of them. The C1-INH concentrate was effective in 6 acute episodes that were detected during the study, as well as in 3 surgical prophylaxis cases (overall use 6,500 U). CONCLUSION: Danazol was effective as prophylactic treatment, but had severe side effects. The C1-INH concentrate was effective both as prophylactic therapy and treatment for acute episodes. An adequate stock of this product will be available at the Pharmacy Department.

[Inhalation administration of nitric oxide during selective pulmonary ventilation decreases the intrapulmonary shunt]. / La administración inhalatoria de óxido nítrico durante la ventilación pulmonar selectiva disminuye el shunt intrapulmonar.

OBJECTIVE: To assess the effects of inhaled nitric oxide (NO) on oxygenation and hemodynamics in patients undergoing lung resection surgery during one-lung ventilation (OPV). PATIENTS AND METHODS: Prospective study of 16 patients aged 62 +/- 10 years scheduled for chest surgery under combined general and epidural anesthesia. During ventilation of only one lung, NO was administered for 15 minutes. Arterial blood and mixed venous blood samples were taken for analysis of blood gases and the calculation of intrapulmonary shunt. Pulmonary and systemic hemodynamic variables were also recorded using a Swan-Ganz catheter at three times: baseline (ventilation of both lungs), OLV, and with OLV plus NO (OLV NO). RESULTS: The most relevant data consisted of a significant decrease in shunt after start of NO inhalation in comparison with the level during OLV (31.1 +/- 0.5% versus 36 +/- 0.6%; p < 0.05). Arterial oxygen pressure decreased significantly during OLV and increased after start of NO (118.9 +/- 53.6 versus 155.4 +/- 78.5 mmHg; p < 0.05). Mean pulmonary artery pressure, pulmonary and systemic vascular resistances, and cardiac index did not change with inhalation of NO. CONCLUSIONS: Inhalational administration of NO during OLV significantly improves arterial oxygenation and decreases intrapulmonary shunt during OLV, without causing hemodynamic or systemic effects.

Displaced stress fractures of the femoral neck in young male adults: a report of twelve operative cases.

The results of 12 operatively treated displaced stress fractures of the femoral neck in young male adults are reported. The mean age of the patients was 19.8 years (range, 19-24 years) and the mean followup period 4.0 years (range, 1-9 years). Sliding hip compression screw was used in ten cases, Jewett nail in one and 130 degrees angled A0-plate in one case. Aseptic necrosis (AN) of the femoral head developed in five cases treated by sliding hip compression screw. It was correlated with increased operative trauma in four patients: open reduction in two, reoperation in one, and osteotomy in one case. Nonunion developed in three cases and it was combined with AN in two cases. In six cases the results were acceptable, but for the last three patients the followup period was only 1-2 years.

Endometrioid adenosarcoma of the bladder arising from endometriosis.

Vesical endometriosis is an uncommon entity characterized by the deposition of benign, hyperplastic endometrial tissue in the bladder. To date, only about 160 cases have been reported in the world literature. More uncommon, however, are case reports of extrauterine malignancies arising from pre-existing endometriosis. We report a case of a large endometrial adenosarcoma in a patient who had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy 10 years previously for endometriosis. To our knowledge this malignancy has never been reported previously to involve the bladder. We review the pathological findings, possible mode of entry into the bladder and current concepts in its treatment.

A single mRNA encodes the alpha 150 and alpha 80/70 forms of the alpha subunit of VLA4.

VLA4 is a cell surface heterodimer (alpha 4 beta 1, CD49d/CD29) which belongs to the integrin family and is involved in cell-extracellular matrix interactions, as well as in intercellular adhesion. Unlike other integrin alpha subunits, the alpha subunit of VLA4 (alpha 4) can appear as a 150-kDa polypeptide (alpha 150), or cleaved into two non-covalently associated polypeptides (alpha 70-80). The relative proportion of each form is highly variable among different cells and is dependent on the state of cellular activation. The alpha 4 cleavage site has recently been shown to occur between residues Arg558-Ser559. We report the isolation of genomic clones encoding the alpha 4 subunit, the location of the cleavage site-encoding nucleotides to a specific exon and the determination of the exon-intron organization around the cleavage site. Comparison with the gpIIb (CD41) and the alpha x (p150,95 alpha, CD11c) genes revealed a similar genomic structure in this region, with exons of similar length separated by introns of identical phase. The structure of the alpha 4 mRNA in cells expressing the alternative forms of alpha 4 has been analyzed by means of reverse transcription-polymerase chain reaction. Our results indicate that the exon encoding the cleavage site is present in alpha 4 mRNA molecules from cells expressing either the alpha 150 or the alpha 70-80 form on the cell surface. Moreover, the structure of the alpha 4 mRNA around the cleavage site does not change during the switch towards the alpha 70-80 form that takes place upon lymphocyte activation. Therefore, both forms of alpha 4 arise from a common mRNA, the alpha 150 form contains the cleavage sequence and the alpha 70-80 form must be generated by a post-translational proteolytic event.

Characterization of the CD11a (alpha L, LFA-1 alpha) integrin gene promoter.

Human lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18, alpha L/beta 2) is a cell surface heterodimer, which, together with Mac-1 (CD11b/CD18, alpha M/beta 2) and p150,95 (CD11c/CD18, alpha X/beta 2), constitutes the leukocyte integrin beta 2 (CD18) subfamily. LFA-1 is the only integrin expressed on all leukocyte lineages and functions both as a key adhesion receptor in immune and inflammatory processes and as a signal-transducing molecule. To elucidate the molecular basis for the leukocyte-restricted expression of LFA-1, the promoter region of the CD11a gene has been isolated and functionally characterized. The 5' region of the CD11a gene exhibits a similar exon/intron organization as the CD11b, CD11c, and VLA-2 alpha genes but is different from that of the genes encoding VLA-4 alpha, VLA-5 alpha, and gpIIb. Several tightly clustered transcription initiation sites have been identified on the CD11a gene, with the major site resembling the "initiator" sequence. Transient expression of CD11a promoter-based reporter gene constructs in both LFA1+ and LFA1- cell lines demonstrated that the fragment spanning from -880 to +83 is involved in the tissue-specific expression of LFA-1. Functional analysis of different fragments within the -880/+83 fragment suggested the presence of negative regulatory elements between -880 and -226 and demonstrated that the proximal region of the CD11a gene promoter exhibits tissue-specific activity.

[Idiopathic retroperitoneal fibrosis]. / Fibrosis retroperitoneal idiopática.

OBJECTIVE: A case of idiopathic retroperitoneal fibrosis in a 34-year-old man with anemia and elevated erythrocyte sedimentation rate is presented. METHODS/RESULTS: Ultrasound, CT and MRI evaluation and pathological study were performed. These diagnostic imaging techniques demonstrated an infiltrating mass in the upper portion of the abdomen which was resected. Histological and immunohistochemical studies of the surgical specimen demonstrated sclerosing retroperitonitis. CONCLUSIONS: Idiopathic retroperitoneal fibrosis (Ormond's disease) is a rare disease entity whose etiology is obscure and is characterized by retroperitoneal fibrosis with inflammatory infiltrates composed of plasma cells, lymphocytes and eosinophils. This case is of interest due to its atypical location, and because the patient was young with no remarkable clinical history and only mild anemia and an elevated erythrocyte sedimentation rate.