Localization and potential role of matrix metalloproteinase-1 and tissue inhibitors of metalloproteinase-1 and -2 in different phases of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) can evolve in prematurely born infants who require mechanical ventilation because of hyaline membrane disease (HMD). The development of BPD can be divided in an acute, a regenerative, a transitional, and a chronic phase. During these different phases, extensive remodeling of the lung parenchyma with re-epithelialization of the alveoli and formation of fibrosis occurs. Matrix metalloproteinase-1 (MMP-1) is an enzyme that is involved in re-epithelialization processes, and dysregulation of MMP-1 activity contributes to fibrosis. Localization of MMP-1 and its inhibitors, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, were investigated in lung tissue obtained from infants who died during different phases of BPD development. In all studied cases (n = 50) type-II pneumocytes were found to be immunoreactive for MMP-1, TIMP-1, and TIMP-2. During the acute and regenerative phase of BPD, type-II pneumocytes re-epithelialize the injured alveoli. This may suggest that MMP-1 and its inhibitors, expressed by type-II pneumocytes, play a role in the re-epithelialization process after acute lung injury. Although MMP-1 staining intensity remained constant in type-II pneumocytes during BPD development, TIMP-1 increased during the chronic fibrotic phase. This relative elevation of TIMP-1 compared with MMP-1 is indicative for reduced collagenolytic activity by type-II pneumocytes in chronic BPD and may contribute to fibrosis. Fibrotic foci in chronic BPD contained fibroblasts immunoreactive for MMP-1 and TIMP-1 and -2. This may indicate that decreased collagen turnover by fibroblasts contributes to fibrosis in BPD development

Cell death during sepsis: integration of disintegration in the inflammatory response to overwhelming infection

Sepsis is a major health problem and a leading cause of death worldwide. In recent years, a crescendo of attention has been directed to the mechanisms of cell death that develop during this disease, since these are viewed as important contributors to the proinflammatory and anti-inflammatory responses associated with poor outcome. Here we discuss mechanisms of cell death evident severe bacterial infection and sepsis including necrosis, apoptosis, pyroptosis, and extracellular trap-associated neutrophil death, with a particular emphasis on lymphocyte apoptosis and its contribution to the immunosuppressed phenotype of late sepsis. Individual bacterial pathogens express virulence factors that modulate cell death pathways and influence the sepsis phenotype. A greater knowledge of cell death pathways in sepsis informs the potential for future therapies designed to ameliorate immune dysfunction in this syndrome

The Dresden Predictor Study of anxiety and depression: objectives, design, and methods

Contains fulltext : 90415.pdf (publisher's version ) (Closed access)The present report describes the objectives, design, and methods of the Dresden Predictor Study (DPS) of anxiety and depression, a prospective epidemiological study investigating anxiety disorders and depression in 3,065 young German women (18-25 years of age). The DPS consists of a baseline and one follow-up investigation separated by approximately 17 months. At both time points, respondents were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) using an extended German version of the Anxiety Disorders Interview Schedule (ADIS-IV-L). In addition to diagnostic assessment, respondents completed a battery of self-report questionnaires that provided detailed information about potential predictors of disorders and a comprehensive dimensional assessment of psychopathology. Results on both response bias in the baseline investigation and effects of dropout at follow-up are presented, and strengths and limitations of the study design are discussed

Oral mucosal microvascular abnormalities: an early marker of bronchopulmonary dysplasia.

7An abnormal pulmonary vasculature has been reported as an important component of bronchopulmonary dysplasia (BPD). We tested the hypothesis of an early abnormal vascular network pattern in infants with BPD. Fifteen infants with BPD (nine boys and six girls; gestational age 27.5 2.0 wk; birth weight 850 125 g) and 15 sex- and gestational age–matched infants (nine boys and six girls; gestational age 27.6 2.6 wk; birth weight 865 135 g) were examined on postnatal days 1 and 28. BPD infants showed a significantly higher prevalence of histologic chorioamnionitis (p 0.009), as well as higher intubation duration (p 0.0004), oxygen supplementation (p 0.0001), and initial illness severity (p 0.0002) than the BPD-negative population. The lower gingival and vestibular oral mucosa was chosen as the study area. The blood vessel area was determined, and the oral vascular networks were characterized by analyzing their complexity (D, at two scales: D 1–46, D 1–15), tortuosity (Dmin), and randomness (L-Z) of the vascular loops. Infants with BPD showed a significantly lower blood vessel area as well as a higher vascular network complexity (D 1–46, D 1–15, and L-Z) than control subjects (p 0.0001). Our findings provide a new early clinical sign in BPD and stress the importance of an early disorder in the oral mucosal vascularization process in the disease pathogenesis.reservedmixedDE FELICE C; LATINI G; S. PARRINI; BIANCIARDI G; TOTI P; KOPOTIC RJ; NULL DM.DE FELICE, C; Latini, G; Parrini, Stefano; Bianciardi, Giorgio; Toti, Paolo; Kopotic, Rj; Null, D. M

Chronic Respiratory Failure in Neonates

The original publication on bronchopulmonary dysplasia (BPD) by Northway and collaborators described a group of preterm infants who after prolonged mechanical ventilation developed chronic respiratory failure and characteristic radiographic findings (Northway et al. 1967). The lung damage was attributed primarily to the use of aggressive positive-pressure ventilation and high inspired oxygen concentrations. Today, with the widespread use of antenatal corticosteroids and the use of postnatal surfactant and less aggressive mechanical ventilation, this severe form of BPD has been replaced by a milder form that presents in the more immature infants who frequently have only mild initial respiratory disease (Charafeddine et al. 1999; Parker et al. 1992; Rojas et al. 1995). Therefore, these infants are not exposed to the very high airway pressures or oxygen concentrations, the two main factors in the pathogenesis of the original form of BPD. This milder form of the disease has been described as “New BPD.” This new presentation has created some inconsistencies and confusion in the definition and the diagnostic criteria of BPD (Bancalari et al. 2003)