Systemic lupus erythematosus in pediatric patients: Pulmonary manifestations.

The pulmonary manifestations of Systemic Lupus Erythematosus (SLE) in pediatric patients are poorly understood and the pulmonary manifestations reported from the adult population are generally extrapolated to the pediatric population. In the present work, the review of 228 files was carried out, in which the pulmonary manifestations, symptoms and antibody levels of the patients treated at the Hospital Regional de Alta Especialidad de Ixtapaluca (HRAEI), State of Mexico, Mexico, were identified. Statistical significance between groups was estimated using the Chi-square and Mann-Whitney U test. The main pulmonary manifestations identified were pleurisy (14 %), pulmonary hemorrhage (3.9 %), pulmonary thromboembolism (0.9 %), acute lupus pneumonitis (0.4 %), pulmonary arterial hypertension (0.4 %), and small lung syndrome (0.4 %). While the initial symptomatology was dyspnea with an incidence of 9.6 %, the mean oxygen saturation in the population was 96.87 %. Pleural effusion was identified as the most frequent pulmonary manifestation in radiographic changes. No statistically significant difference was found in antibody levels when comparing the groups. The most common pulmonary manifestation associated with SLE is pleurisy, however, the range of pulmonary manifestations in this type of patient can be very varied, as well as the presentation of each of them.

Anti-Inflammatory Potential of 1-Nitro-2-Phenylethylene.

Inflammation is a reaction of the host to infectious or sterile stimuli and has the physiological purpose of restoring tissue homeostasis. However, uncontrolled or unresolved inflammation can lead to tissue damage, giving rise to a plethora of chronic inflammatory diseases, including metabolic syndrome and autoimmunity pathologies with eventual loss of organ function. Beta-nitrostyrene and its derivatives are known to have several biological activities, including anti-edema, vasorelaxant, antiplatelet, anti-inflammatory, and anticancer. However, few studies have been carried out regarding the anti-inflammatory effects of this class of compounds. Thereby, the aim of this study was to evaluate the anti-inflammatory activity of 1-nitro-2-phenylethene (NPe) using in vitro and in vivo assays. Firstly, the potential anti-inflammatory activity of NPe was evaluated by measuring TNF-α produced by human macrophages stimulated with lipopolysaccharide (LPS). NPe at non-toxic doses opposed the inflammatory effects induced by LPS stimulation, namely production of the inflammatory cytokine TNF-α and activation of NF-κB and ERK pathways (evaluated by phosphorylation of inhibitor of kappa B-alpha [IκB-α] and extracellular signal-regulated kinase 1/2 [ERK1/2], respectively). In a well-established model of acute pleurisy, pretreatment of LPS-challenged mice with NPe reduced neutrophil accumulation in the pleural cavity. This anti-inflammatory effect was associated with reduced activation of NF-κB and ERK1/2 pathways in NPe treated mice as compared to untreated animals. Notably, NPe was as effective as dexamethasone in both, reducing neutrophil accumulation and inhibiting ERK1/2 and IκB-α phosphorylation. Taken together, the results suggest a potential anti-inflammatory activity for NPe via inhibition of ERK1/2 and NF-κB pathways on leukocytes.

Pleuropulmonary involvement in patients with systemic lupus erythematosus from a Latin American inception cohort (GLADEL).

Objectives The objectives of this study were to examine the demographic and clinical features associated with the occurrence of pleuropulmonary manifestations, the predictive factors of their occurrence and their impact on mortality in systemic lupus erythematosus (SLE) patients. Materials and methods The association of pleuropulmonary manifestations with demographic and clinical features, the predictive factors of their occurrence and their impact on mortality were examined in GLADEL patients by appropriate univariable and multivariable analyses. Results At least one pleuropulmonary manifestation occurred in 421 of the 1480 SLE patients (28.4%), pleurisy being the most frequent (24.0%). Age at SLE onset ≥30 years (OR 1.42; 95% CI 1.10-1.83), the presence of lower respiratory tract infection (OR 3.19; 95% CI 2.05-4.96), non-ischemic heart disease (OR 3.17; 95% CI 2.41-4.18), ischemic heart disease (OR 3.39; 95% CI 2.08-5.54), systemic (OR 2.00; 95% CI 1.37-2.91), ocular (OR 1.58; 95% CI 1.16-2.14) and renal manifestations (OR 1.44; 95% CI 1.09-1.83) were associated with pleuropulmonary manifestations, whereas cutaneous manifestations were negatively associated (OR 0.47; 95% CI 0.29-0.76). Non-ischemic heart disease (HR 2.24; 95% CI 1.63-3.09), SDI scores ≥1 (OR 1.54; 95% CI 1.10-2.17) and anti-La antibody positivity (OR 2.51; 95% CI 1.39-4.57) independently predicted their subsequent occurrence. Cutaneous manifestations were protective of the subsequent occurrence of pleuropulmonary manifestations (HR 0.62; 95% CI 0.43-0.90). Pleuropulmonary manifestations independently contributed a decreased survival (HR: 2.79 95% CI 1.80-4.31). Conclusion Pleuropulmonary manifestations are frequent in SLE, particularly pleuritis. Older age, respiratory tract infection, cardiac, systemic and renal involvement were associated with them, whereas cutaneous manifestations were negatively associated. Cardiac compromise, SDI scores ≥1 and anti-La positivity at disease onset were predictive of their subsequent occurrence, whereas cutaneous manifestations were protective. They independently contributed to a decreased survival in these patients.

Lupus pleuritis: a relevant risk factor for pulmonary tuberculosis.

The objective of the study was to evaluate risk factors for pulmonary tuberculosis in systemic lupus erythematosus (SLE). Clinical/laboratorial features of 1283 SLE patients (ACR criteria) followed at the Lupus Clinic were obtained from the electronic register database from 2001 to 2009. Pulmonary tuberculosis was diagnosed in 20 patients (1.6%) (TB+ group). As control group (TB-), 40 patients without tuberculosis matched for age, gender, ethnicity, age at SLE diagnosis, and disease duration were arbitrarily selected. All 20 patients of the TB+ group presented confirmed pulmonary tuberculosis from 1 to 23 years after SLE diagnosis (7.6 ± 8.1 years). Frequencies of previous SLE involvements (cutaneous, articular, hematological, renal, pericarditis, pneumonitis, and central nervous system) were alike in TB+ and TB- groups (p > 0.05). In contrast, prior pleuritis was more frequent in the TB+ group (40% vs. 5%, p = 0.001). In fact, pulmonary tuberculosis was diagnosed in 8/10 patients with previous pleuritis. Immunosuppressive and corticosteroid therapies at the moment of tuberculosis diagnosis were also similar in both groups (p > 0.05). We have identified pleuritis as a relevant risk factor for pulmonary tuberculosis, suggesting that previous pleural injury is a critical part of the complex interplay between altered immune system, socio-economic conditions, and increased susceptibility to this mycobacterial infection.

[Pericardial effusion and pleural serositis in patients with severe preeclampsia and HELLP syndrome]. / Derrame pericárdico y serositis pleural en pacientes con preeclampsia severa y síndrome HELLP. Reporte de dos casos.

The syndrome pre-eclampsia/eclampsia is a frequent entity in the obstetrical pathology and acquires interest to take to the patients to a critical state. It has repercussion in all the organism by his complications. The definitive treatment of pre-eclampsia/eclampsia is the interruption of the pregnancy. The pericardial effussion as severe complication of pre-eclampsia and Sx de HELLP is a little frequent entity. Few cases reported in Literature exists. In the Hospital Angeles Pedregal, two cases of patients embarrassed without antecedents of previous picture hypertensive, complicated are reported with severe pre-eclampsia and HELLP syndrome class II of Martin which developed pericardial effussion without presence of tamponade. The knowledge of the behavior of this cardiovascular complication as well as the multidisciplinary and integral handling, are without a doubt the best form to modify the evolution and to avoid the appearance of tamponade. The acute pericardial effussion can get to mean a medical urgency that puts in danger the life. Mainly when the intrapericardic pressure so is lifted that the heart is compressed and the diastolic pressures ventricular lefts and right are increased and in the absence of preexisting cardiac pathology, these pressures get to equal itself. This complication little frequents must be had in mind like more of the haemodynamic complications.

Escrofuloderma a focos mútiples: descripción de un caso / Implies multiple foci Scrofuloderma to: a case

La tuberculosis (TBC) es producida por el Mycobacterium tuberculosis. Es escrofuloderma es una de sus formas cutáneas e integra el grupo de las TBC colicuativas. El empiema tuberculoso puede ocasionar inflamación de los tejidos de la peripleura o “peripleuritis”, con formación de abscesos fríos peripleuríticos; en su evolución puede abrirse camino a través de los planos profundos hacia piel, constituyendo el denominado empiema por necesidad, que se manifiesta clínicamente con tumoraciones cutáneas que pueden evocar lipomas. Se presenta el caso de un paciente con coexistencia de escrofuloderma a focos múltiples (óseo y ganglionar) y empiema por necesidad.

The allergic inflammatory reaction in neonatal streptozotocininduced diabetic rats: evidence of insulin resistance and microvascular dysfunction.

OBJECTIVE: To investigate the allergic reaction in neonatal streptozotocin (nSTZ)-induced diabetes mellitus. MATERIAL: Male newborn Wistar rats were made diabetic by the injection of streptozotocin (160 mg/kg, i. p.) and used 8 weeks thereafter. TREATMENT: Animals were sensitized against ovalbumin (OA, 50 microg and Al(OH)3, 5 mg, s. c.) and challenged 14 or 21 days thereafter. METHODS: OA-induced airway inflammation and OA-induced pleurisy models were used to investigate leukocyte migration (total and differential leukocyte counts) and lung vascular permeability (Evans blue dye extravasation). RESULTS: nSTZ-diabetic rats presented glucose intolerance and insulin resistance. Relative to controls, nSTZ rats exhibited a 30% to 50% reduction in lung vascular permeability. Leukocyte infiltration in both models of allergen-induced inflammation, and number of pleural mast cells did not differ between groups. CONCLUSIONS: Data suggest that the reduction of allergic inflammatory reactions in nSTZ rats is restricted to microvascular dysfunctions and associated, probably, with insulin resistance in lung microvascular endothelium.

Chlorpropamide treatment restores the reduced carrageenan-induced paw edema and pleural exudate volume in diabetic rats.

OBJECTIVE AND DESIGN: Knowing that hyperglycemia is a hallmark of vascular dysfunction in diabetes and that neonatal streptozotocin-induced diabetic rats (n-STZ) present reduced inflammatory response, we decided to evaluate the effect of chlorpropamide-lowered blood glucose levels on carrageenan-induced rat paw edema and pleural exudate in n-STZ. MATERIALS: Diabetes was induced by STZ injection (160 mg/kg, ip) in neonates (2-day-old) Wistar rats. TREATMENT: n-STZ diabetic rats were treated with chlorpropamide (200mg/kg, 15d, by gavage) 8 weeks after STZ injection. METHODS: Carrageenan-induced paw edema and pleural exudate volumes were assessed concomitantly with peripheral and exudate leukocyte count. We also evaluated the expression of inducible nitric oxide synthase (iNOS) in lungs of all experimental groups. RESULTS: Chlorpropamide treatment improved glucose tolerance, beta-cell function (assessed by HOMA-beta), corrected paw edema, and pleural exudate volume in n-STZ. Neither leukocyte count nor iNOS expression were affected by diabetes or by chlorpropamide treatment. CONCLUSION: Chlorpropamide treatment by restoring beta-cell function, reducing blood sugar levels, and improving glucose tolerance might be contributing to the correction of the reduced inflammatory response tested as paw edema and pleural exudate in n-STZ diabetic rats.

Suppressive effects of nitric oxide-releasing prednisolone NCX-1015 on the allergic pleural eosinophil recruitment in rats.

BACKGROUND: The addition of a nitric oxide (NO)-releasing moiety to prednisolone was shown to enhance the anti-inflammatory activity of this glucocorticoid in some experimental conditions, but its effectiveness in the context of eosinophilic inflammation remains to be elucidated. OBJECTIVE: This study compared the anti-inflammatory effect of prednisolone to a NO-releasing derivative of prednisolone, NCX-1015, using a model of allergen-evoked eosinophil recruitment in rats. The efficacy of a NO-donor compound, DETA-NONOate, was also assessed for comparison. METHODS: Wistar rats were actively sensitized with Al(OH)(3) plus ovalbumin and 14 days later challenged with antigen intrapleurally. Treatments were performed locally 1 h before challenge. Cysteinyl-leucotrienes (Cys-LT) and eotaxin were measured by ELISA. RESULTS: Antigen challenge induced an eosinophil infiltration at 12 h, maximal at 24 h. It also caused an increase in the levels of Cys-LTs in the pleural exudate and in the expression of 5-lipoxygenase (5-LO) in infiltrated leucocytes at 6 h, peaking at 12 h and persisting for at least 24 h. Treatment with equimolar doses of prednisolone and NCX-1015 inhibited the late eosinophil infiltration, although the dose required to produce maximal inhibition was about one-tenth that of prednisolone. Cys-LT generation and 5-LO expression were inhibited by NCX-1015 but not by prednisolone. Treatment with prednisolone combined with the NO-donor DETA-NONOate led to a greater inhibition of the eosinophilia and Cys-LT generation as compared with either drug alone. Administration of the steroid receptor antagonist RU 486, 1 h before prednisolone and NCX-1015, abolished the inhibitory effect of the former, under conditions where it only partially affected the latter. CONCLUSIONS: Our findings indicate that NCX-1015 provided a greater anti-inflammatory effect than prednisolone on the allergic eosinophil recruitment in rats, suggesting that NO-releasing steroids can be considered as a promising therapeutic approach to allergic diseases.

Acute immune and non-immune inflammatory response in spontaneously hypertensive rats and normotensive rats. Role of endogenous nitric oxide.

UNLABELLED: The present study investigated the acute inflammatory response (increase in vascular permeability and leukocytes migration) in the pleura of spontaneously hypertensive rats (SHR) and normotensive rats (NTR), using two different stimulus: carrageenan and active anaphylaxis. In addition, the role of endogenous nitric oxide in these responses was investigated. RESULTS: The inflammatory response induced by intrapleural carrageenan injection in SHR developed similarly to that in NTR. Treatment with L-NAME, reduced the intensity of this response in both groups of rats. The inflammatory response induced by active anaphylaxis in SHR and NTR was different. The increase in vascular permeability occurred later in the SHR compared to NTR. The number of leukocyte present in inflammatory exudates was increased at 4 h in both groups of rats. L-NAME treatment did not inhibit exudation at the intervals under analysis, however, reduced the number of mononuclear cells in the inflammatory exudate of SHR. CONCLUSION: The development of the inflammatory response in SHR differs from that in NTR, depending on the nature of the inflammatory stimulus. Endogenous NO plays a clear role in carrageenan-induced inflamma-tion, but not in immunologically mediated inflammation in the analyzed period.

Alloxan diabetes reduces pleural mast cell numbers and the subsequent eosinophil influx induced by allergen in sensitized rats.

Alloxan damages insulin-producing cells and has been used as an inducer of experimental diabetes in several animal species. In this study, administration of alloxan (40 mg/kg, i.v.) to rats was followed by a selective and time-dependent reduction in the number of pleural mast cells (50 +/- 2.2%, p < 0.01; mean +/- SEM), while mononuclear cell and eosinophil counts were not altered. As compared to naive rats, the reduction in mast cell numbers was first noted 48 h following alloxan administration and remained unaltered for at least 60 days. It is noteworthy, that the depletion in the mast cell population was not accompanied by alterations in the total amount of histamine stored per cell. Sensitized rats turned diabetic by alloxan treatment performed 72 h before challenge showed a less pronounced antigen-induced mast cell degranulation compared to nondiabetic rats. Moreover, rats injected with alloxan 72 and 48 but not 24 h before challenge, reacted to allergenic challenge with 50% reduction in the number of eosinophils recruited to the pleural cavity within 24 h. We found that the less pronounced eosinophil accumulation did not relate to an intrinsic cell locomotor abnormality since eosinophils from diabetic rats presented similar chemotactic responses to LTB4 and PAF in vitro as compared to matching controls. Insulin (3 IU/rat) restored basal levels of mast cells and reversed the subsequent inhibition of allergen-induced pleural eosinophilia, suggesting a causative relationship between these phenomena. Treatment with insulin also significantly increased the number of mast cells in the pleural cavity of naive rats (from 637 +/- 57 to 978 +/- 79 x 10(3) cells/cavity, p < 0.001). Consistently, previous depletion of mast cells by means of local treatment with compound 48/80 significantly reduced the antigen-induced eosinophil recruitment in sensitized animals. We conclude that the reduction in the pleural mast cell population noted in alloxan-treated rats could be directly implicated in the diminished pleural eosinophil influx following allergen challenge. This hyporesponsiveness is independent of an intrinsic abnormality of cell chemotaxis, but can be imitated by local mast cell depletion.

Local exposure to salbutamol or Bt2 cyclic AMP inhibits pleural exudation and leukocyte influx caused by antigen in rats.

The local effect of salbutamol and N6,2'-O-dibutyryl adenosine 3':5'-cyclic monophosphate (Bt2 cyclic AMP) on the rat pleural inflammation caused by allergen was investigated. Antigen (ovalbumin, 12 micrograms/cavity) intrathoracically administered to immunized rats led to a marked pleural protein extravasation and leukocyte infiltration, as attested by the quantification of protein and enumeration of leukocytes recovered from the pleural cavity. Salbutamol (10-40 micrograms/cavity) and the cell-permeable cyclic AMP analogue, Bt2 cyclic AMP (20-160 micrograms/cavity), injected 1 h and 5 min before the antigen, respectively, inhibited the exudation occurring within 30 min, and neutrophil and eosinophil accumulation occurring 4 and 24 h, respectively. The late eosinophilia was also markedly attenuated by salbutamol administered 10 min post-challenge, when mast cells had already been degranulated. Pretreatment with the beta-adrenoceptor antagonist propranolol (1 mg/kg, i.v.) failed to modify the inhibitory effect of Bt2 cyclic AMP, but abolished the blockade caused by salbutamol of leukocyte infiltration under conditions where the salbutamol anti-exudatory activity was impaired to about 80%. In another set of experiments, salbutamol (20 and 40 micrograms/cavity) markedly inhibited the exudation caused by histamine and 5-hydroxytryptamine (5-HT) which, though to a lesser extent, was also sensitive to Bt2 cyclic AMP (80 micrograms/cavity). As observed with allergic pleurisy, propranolol impaired the inhibition by salbutamol of histamine- and 5-HT-induced exudation, whereas the Bt2 cyclic AMP inhibition was not affected. We conclude that salbutamol and Bt2 cyclic AMP share the ability to inhibit pleural exudation and leukocyte recruitment caused by allergen in immunized rats, suggesting that the anti-inflammatory effect of salbutamol may be mediated by a cyclic AMP signaling pathway, probably via beta 2-adrenoceptor activation.

Pasteurella multocida fimbriada como agente desencadenante de pleuritis y neumonía fibrinosa en cerdos / Fimbriated Pasteurella multocida as etiological agent of pleuritis and fibrinous pneumonia in pigs

Pasteurella multocida tiene cuatro diferentes tipos capsulares (A, B, D y E); A y D son los que caudan problemas en cerdos. El tipo A causa neumonía y el D, rinitis; este tipo capsular produce tpxona, que destruye los cornetes nasales. En 1983, se aislaron dos cepas de P. multocida tipo A en dos granjas con problemas respiratorios, como pleuritis, pericarditis, neumonía fibrinosa y pequeños abscesos. Estas cepas de P. multocida se identificaron con A52 y A59, las que se observaron también al microscopio electrónico observándose pequeñas microvellocidades en la superificie. En inoculaciones experimentales con estos tipos, en relación con los que normalmente ocasionan problemas respiratorios en cerdos, se observó que tales cepas desencadenan problemas más severos de tipo pleuroneumónico abscedativo.

Effect of azelastine on platelet-activating factor and antigen-induced pleurisy in rats.

The interference of azelastine with pleurisy induced by antigen was investigated in actively sensitized rats. The antigenic challenge (ovalbumin, 12 micrograms/cavity) caused early plasma leakage, which peaked within 4 h, accompanied by intense neutrophil infiltration. Pleural exudate decayed 24 h after antigen provocation, when a long-lasting increase in the number of resident eosinophils was observed. Oral pretreatment with azelastine (1-10 mg/kg) dose dependently inhibited the vasopermeation (ED50 = 4.2 mg/kg) and reduced the pleural exudate (ED50 = 6.8 mg/kg) induced by the antigen. In contrast, azelastine (10 mg/kg) failed to modify the neutrophil influx observed at 4 h and the eosinophil accumulation detected at 24 h. Azelastine was also effective against rat pleurisy induced by either platelet-activating factor (PAF-acether), histamine or serotonin. It reduced exudation and the increase in the number of mononuclear cells, neutrophils and eosinophils observed 6 h after PAF-acether. Nevertheless, antagonism of PAF-acether may not be relevant to the inhibition observed in the present model of allergic pleurisy, as the inhibition was refractory to three distinct PAF-acether receptor antagonists. In contrast, like azelastine, the histamine H1 receptor antagonist meclizine and the dual histamine and serotonin receptor antagonist cyproheptadine blocked antigen-induced exudation and failed to interfere with cell influx. We conclude that the anti-exudatory activity of oral azelastine on antigen-induced pleurisy is consistent with it exerting direct effects against vasoactive amines, but is not related to an effect against leucocyte infiltration nor to its ability to inhibit PAF-acether.

[Spontaneous bacterial pleuritis in 3 patients with liver cirrhosis]. / Pleuritis bacteriana espontánea en tres pacientes con cirrosis hepática.

We report 4 episodes of spontaneous bacterial pleuritis observed in 3 patients with liver cirrhosis complicated by ascites and pleural effusion. This infection mimics spontaneous bacterial peritonitis. Three episodes were successfully treated. Proposed pathogenesis, diagnostic methods and therapy are discussed.

Bradykinin induces eosinophil accumulation in the rat pleural cavity.

Intrathoracic injections of bradykinin (1-100 micrograms/cavity) induced a dose-dependent increase in the number of eosinophils recovered from the rat pleural cavity 24 h later. Eosinophilia by bradykinin was preceded by a marked pleural neutrophil influx within 6 h and was absent only 72 h following stimulation. Bradykinin (10(-9)-10(-5) M) failed to induce in vitro eosinophil chemotaxis, indicating that its in vivo effect must be mediated by an intermediate messenger. BW 755C (25 mg/kg) and the more selective lipoxygenase inhibitor BW A4C (20 micrograms/cavity) suppressed the pleural eosinophilia induced by bradykinin (50 micrograms/cavity), whereas the platelet-activating factor (PAF)-acether antagonist BN 52021 was inactive. We conclude that bradykinin is able to attract eosinophil in vivo by a mechanism independent of PAF-acether and sensitive to the blockage of the lipoxygenase pathway.