IL-6 and G-CSF levels in amniotic fluid during the second trimester in normal and abnormal pregnancies

Activity levels of cytokines were measured by stimulation of the cell lines NFS-60, 7TD1, and TF-1. In 39 samples of amniotic fluid, levels of Granulocyte-Stimulating Factor (G-CSF) were 1434±2063 (mean±SD) and of Interleukin (IL-6) 546±1071 pg/ml; Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) was not detectable. IL-6 was correlated to G-CSF (r=0.3; p=0.003). G-CSF (p=0.0002) and IL-6 (p=0.006) were influenced by Alpha-Fetoprotein (AFP) and G-CSF by rhesus-incompatibility (p=0.0004). These findings suggest that cytokines such as IL-6 and G-CSF play some role in physiological and pathological pregnancy.Abbreviations G-CSF granulocyte-colony stimulating factor - GM-CSF granulocyte-macrophage colony stimulating factor - M-CSF macrophage-colony stimulating factor - CSF colonystimulating factor - IL-6 interleukin-6 - IL-11 interleukin-11 - AFP alpha-fetoprotein - NFS-60 cell line - 7TD1 cell line - TF-l cell line - rh recombinant human - MTT 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyl tetrazolium bromide - FCS fetal calf serum - RPMI 1640 nutrient solution - ATCC American Tissue Culture Collection Correspondence to: E. Weimann     

Transfer of the HIV-1 cyclophilin-binding site to simian immunodeficiency virus from Macaca mulatta can confer both cyclosporin sensitivity and cyclosporin dependence

HIV-1 specifically incorporates the peptidyl prolyl isomerase cyclophilin A (CyPA), the cytosolic receptor for the immunosuppressant cyclosporin A (CsA). HIV-1 replication is inhibited by CsA as well as by nonimmunosuppressive CsA analogues that bind to CyPA and interfere with its virion association. In contrast, the related simian immunodeficiency virus SIV_mac, which does not interact with CyPA, is resistant to these compounds. The incorporation of CyPA into HIV-1 virions is mediated by a specific interaction between the active site of the enzyme and the capsid (CA) domain of the HIV-1 Gag polyprotein. We report here that the transfer of HIV-1 CA residues 86–93, which form part of an exposed loop, to the corresponding position in SIV_mac resulted in the efficient incorporation of CyPA and conferred an HIV-1-like sensitivity to a nonimmunosuppressive cyclosporin. HIV-1 CA residues 86–90 were also sufficient to transfer the ability to efficiently incorporate CyPA, provided that the length of the CyPA-binding loop was preserved. However, the resulting SIV_mac mutant required the presence of cyclosporin for efficient virus replication. The results indicate that the presence or absence of a type II tight turn adjacent to the primary CyPA-binding site determines whether CyPA incorporation enhances or inhibits viral replication. By demonstrating that CyPA-binding-site residues can induce cyclosporin sensitivity in a heterologous context, this study provides direct in vivo evidence that the exposed loop between helices IV and V of HIV-1 CA not merely constitutes a docking site for CyPA but is a functional target of this cellular protein.     

Inhalation of the Phosphodiesterase-3 Inhibitor Milrinone Attenuates Pulmonary Hypertension in a Rat Model of Congestive Heart Failure

Background: Most patients with congestive heart failure (CHF) develop pulmonary venous hypertension, but right ventricular afterload is frequently further elevated by increased pulmonary vascular resistance. To investigate whether inhalation of a vasodilatory phosphodiesterase-3 inhibitor may reverse this potentially detrimental process, the authors studied the effects of inhaled or intravenous milrinone on pulmonary and systemic hemodynamics in a rat model of CHF.

Methods: In male Sprague-Dawley rats, CHF was induced by supracoronary aortic banding, whereas sham-operated rats served as controls. Milrinone was administered as an intravenous infusion (0.2-1 [mu]g [middle dot] kg body weight-1 [middle dot] min-1) or by inhalation (0.2-5 mg/ml), and effects on pulmonary and systemic hemodynamics and lung water content were measured.

Results: In CHF rats, intravenous infusion of milrinone reduced both pulmonary and systemic arterial blood pressure. In contrast, inhalation of milrinone predominantly dilated pulmonary blood vessels, resulting in a reduced pulmonary-to-systemic vascular resistance ratio. Repeated milrinone inhalations in 20-min intervals caused a stable reduction of pulmonary artery pressure. No hemodynamic effects were detected when 0.9% NaCl was administered instead of milrinone or when milrinone was inhaled in sham-operated rats. No indications of potentially adverse effects of milrinone inhalation in CHF, such as left ventricular volume overload, were detected. Moreover, lung edema was significantly reduced by repeated milrinone inhalation.     

Sonographic diagnosis of an aneurysm of the superior mesenteric artery

This is a report on a patient with a mycotic aneurysm of the superior mesenteric artery proved by histology. Because of a marked intolerance of contrast media we abstained from angiography. It is shown that real-time sonography gives a definite diagnosis, if the multiple vascular structures of the upper abdomen are precisely identified.     

Congenital NOS2 deficiency protects mice from LPS-induced hyporesponsiveness to inhaled nitric oxide

BACKGROUND: In animal models, endotoxin (lipopolysaccharide) challenge impairs the pulmonary vasodilator response to inhaled nitric oxide (NO). This impairment is prevented by treatment with inhibitors of NO synthase 2 (NOS2), including glucocorticoids and L-arginine analogs. However, because these inhibitors are not specific for NOS2, the role of this enzyme in the impairment of NO responsiveness by lipopolysaccharide remains incompletely defined. METHODS: To investigate the role of NOS2 in the development of lipopolysaccharide-induced impairment of NO responsiveness, the authors measured the vasodilator response to inhalation of 0.4, 4, and 40 ppm NO in isolated, perfused, and ventilated lungs obtained from lipopolysaccharide-pretreated (50 mg/kg intraperitoneally 16 h before lung perfusion) and untreated wild-type and NOS2-deficient mice. The authors also evaluated the effects of breathing NO for 16 h on pulmonary vascular responsiveness during subsequent ventilation with NO. RESULTS: In wild-type mice, lipopolysaccharide challenge impaired the pulmonary vasodilator response to 0.4 and 4 ppm NO (reduced 79% and 45%, respectively, P < 0.001), but not to 40 ppm. In contrast, lipopolysaccharide administration did not impair the vasodilator response to inhaled NO in NOS2-deficient mice. Breathing 20 ppm NO for 16 h decreased the vasodilator response to subsequent ventilation with NO in lipopolysaccharide-pretreated NOS2-deficient mice, but not in lipopolysaccharide-pretreated wild-type, untreated NOS2-deficient or untreated wild-type mice. CONCLUSIONS: In response to endotoxin challenge, NO, either endogenously produced by NOS2 in wild-type mice or added to the air inhaled by NOS2-deficient mice, is necessary to impair vascular responsiveness to inhaled NO. Prolonged NO breathing, without endotoxin, does not impair vasodilation in response to subsequent NO inhalation. These results suggest that NO, plus other lipopolysaccharide-induced products, are necessary to impair responsiveness to inhaled NO in a murine sepsis model.     

Psychological comorbidity in children and adolescents with chronic somatic diseases

This article analyzes emotional and behavioral problems in children and adolescents with chronic somatic disorders. Within the German Health Interview and Examination Survey for Children and Adolescents (Kinder- und Jugendgesundheitssurvey, KIGGS), chronic somatic conditions and obesity were assessed in 11,529 children and adolescents aged 7?C17?years old. Special health care needs (CSHCN), emotional and behavioral problems (SDQ), as well as personal, familial, and social resources were surveyed. About 10.8% of the respondents displayed special health care needs and declared a chronic somatic disorder. Of these cases, 20.6% were classified as abnormal in the SDQ (non-somatic conditions: 6.4%). In a logistic regression analysis, male gender (OR=2.0), low socioeconomic status (Winkler index; OR=2.6), family structure (OR>1), and deficits in familial (OR=2.4) and personal (OR=2.1) resources were found to be significantly associated with psychological comorbidity in chronic somatic conditions. The results confirmed previous findings. Especially socioeconomic, structural, and functional aspects of a family have to be considered in the development and prevention of psychological comorbidity in chronic somatic conditions in childhood and adolescence.     

Substantial regional differences in the biomechanical behavior of molar treated with selective caries tissue removal technique: a finite element study

ObjectivesSelective caries removal (SCR) is recommended over non-selective removal for managing deep carious lesions to avoid pulp exposure and maintain pulp vitality. During SCR, residual carious dentin is left behind and sealed beneath the restoration. The biomechanical effects of such residual lesions on the restored tooth remain unclear and were assessed using finite element modeling (FEM).MethodsBased on μ-CT images of a healthy permanent human third molar, we developed five finite element models. Generic class I and II cavity restorations were modeled where residual lesions of variable sizes were either left or fully removed on occlusal and proximal surfaces. The cavities were restored with adhesive composite. All 3D-FE models were compared with a model of a healthy, non-treated molar. A vertical load of 100 N was applied onto the occlusal surface.ResultsRegardless of the lesion size, in molars with occlusal lesions higher mean stresses were predicted along the filling-lesion interface than in all other models. The smallest occlusal lesion (Ø₁ = 1 mm) resulted in the highest maximum stresses at the filling-lesion interface with large stress concentrations at the filling walls indicating failure risk. In conclusion, lesion site and extent are influencing parameters affecting the filling-lesion interactions and thus the biomechanical behavior of the tooth after SCR.SignificanceRetaining carious lesions around the pulpal floor affects the deformation and stress states in tooth-filling complexes. The higher stresses observed in molars with occlusal lesions may affect restoration stability and longevity. Suprisingly, more extended occlusal lesions may provide a more favorable tooth performance than less extended ones. In contrast, in molars with proximal lesions the residual lesion had only limited effect on the tooth’s biomechanical condition.