New experimental melting properties as access for predicting amino-acid solubility

The properties of melting are required for the prediction of solubility of solid compounds. Unfortunately, direct determination of the enthalpy of fusion and melting temperature by using conventional DSC or adiabatic calorimetry is often not possible for biological compounds due to decomposition during the measurement. To overcome this, fast scanning calorimetry (FSC) with scanning rates up to 2 × 10⁴ K s⁻¹ was used in this work to measure the melting parameters for l-alanine and glycine. The enthalpy of fusion and melting temperature (extrapolated to zero heating rate) were Δ_fusH = (22 ± 5) kJ mol⁻¹ and T_fus = (608 ± 9) K for l-alanine, and Δ_fusH = (21 ± 4) kJ mol⁻¹ and T_fus = (569 ± 7) K for glycine. These melting properties were used in the modeling framework PC-SAFT to predict amino-acid solubility in water. The pure-component PC-SAFT parameters and one binary parameter were taken from literature, in which these parameters were fitted to solubility-independent thermodynamic properties such as osmotic coefficients or mixture densities. It was shown that this allowed accurately predicting amino-acid solubility in water over a broad temperature range. The combined methodology of PC-SAFT and FSC proposed in this work opens the door for predicting solubility of molecules that decompose before melting.

New experimental melting properties combined with PC-SAFT allow quantitative solubility predictions of amino acids in water.     

Impacts and patterns of disturbed gastrointestinal function in critically ill patients

Disordered upper gastrointestinal tract motility occurs frequently in intensive care unit patients and often represents a substantial treatment challenge. In addition to specific complications such as pulmonary aspiration and diarrhea, abnormal gastrointestinal motility is a limiting factor for delivery and success of enteral nutrition. The pathophysiologies involved are incompletely understood because of the difficulties of making measurements of gastrointestinal function in critically ill patients. With the recent development of techniques that overcome some of these difficulties, the prospects are brighter for significant advances in this field.     

Enhanced neutrophil extravasation and rapid progression of proteoglycan-induced arthritis in TSG-6-knockout mice

OBJECTIVE: To gain insight into the mechanisms of the antiinflammatory effect of tumor necrosis factor alpha (TNFalpha)-induced protein 6 (Tnfip6) in arthritis, using Tnfip6-deficient animals. METHODS: TNFalpha-stimulated gene 6 (TSG-6) coding for Tnfip6 was disrupted. Tnfip6-deficient mice were backcrossed into proteoglycan-induced arthritis (PGIA)-susceptible BALB/c mice, and arthritis was induced by systemic immunization with cartilage proteoglycan (PG). Thioglycollate-induced sterile peritonitis was also assessed, to monitor the early events of neutrophil extravasation in wild-type and Tnfip6-deficient mice in the presence or absence of treatment with recombinant murine Tnfip6. RESULTS: The onset of PGIA was similar, but progression and severity were significantly greater, in Tnfip6-deficient mice compared with wild-type BALB/c mice. However, this was not associated with enhanced T or B cell responses to cartilage PGs, but rather, an early and more extensive infiltration of the synovium with neutrophil leukocytes was the most prominent histopathologic feature of PGIA in Tnfip6-deficient mice. This was accompanied by elevated serum levels of interleukin-6 and amyloid A, and significantly increased activities of the enzymes plasmin, myeloperoxidase, and neutrophil elastase in the inflamed paw joints of Tnfip6-null mice, when compared with that of the wild-type littermates. Loss of control over several components of inflammation resulted in extensive and rapid cartilage degradation, bone erosion, joint ankylosis, and deformities in Tnfip6-null animals. In support of the antiinflammatory effect of Tnfip6 via the inhibition of polymorphonuclear (PMN) cell efflux, neutrophil invasion during thioglycollate-induced peritonitis was 2-fold higher in Tnfip6-deficient animals than in wild-type animals, but was dramatically suppressed by intravenous injection of recombinant murine Tnfip6. CONCLUSION: Tnfip6 is a multifunctional antiinflammatory protein that is produced at the site of inflammation and can be retained by the hyaluronan-rich extracellular matrix. A major effect of Tnfip6 is the inhibition of the extravasation of PMN cells, predominantly neutrophils, into the site of inflammation, most likely via a CD44/hyaluronan/Tnfip6-mediated blocking mechanism.     

Electron Microscopic Characteristics of β2-Microglobulin Amyloid Deposits in Long-Term Haemodialysis

The electron microscopic features of β2-microglobulin amyloid, deposited in the synovial membrane, are presented and discussed. The patient, a 69-year-old woman underwent chronic hemodialysis for 3 years. Because of constant pain and destructive arthropathy, endoprosthesis of the hip joints were implanted. Extra- and intracellular filamentous–fibrillar amyloid deposits have been demonstrated in ultrathin sections. The extracellular amyloid deposits showed a loose, filamentous or fibrillar structure at the periphery and a dense central core. The loose, filamentous structure may represent an early stage of fresh, newly deposited β2-microglobulin amyloid, while the condensed and fragmented amyloid filaments may be an advanced “mature” stage of amyloid deposition.     

Ultrastructural Identification of Primary Tumor Site from Bone Metastases

The value of electron microscopy is demonstrated by ultrastructural identification of primary tumor site from bone metastases in 2 patients.     

Elevated Complement Factor H Levels in Asthmatic Sputa

Background

The alternative pathway of the complement system is known to play a role in the generation of asthmatic airway inflammation, but its regulatory complement protein, factor H has not been investigated in this disease.

Purpose

Our aim was to determine the local bronchial complement factor H (CFH) levels in asthma, and to investigate its relationship with complement activation, systemic CFH concentrations and clinical characteristics of patients.

Methods

Induced sputum and plasma were collected from 21 healthy and 26 asthmatic subjects, and complement factor H and SC5b-9 concentrations were assessed by ELISA. Total protein concentrations were determined by biuret-reaction based microassay system from induced sputa.

Results

CFH was detectable in 81 % of healthy and 100 % of asthmatic subjects, while SC5b-9 exceeded the detection limit in 62 % of healthy subjects and 85 % of asthmatic patients. Sputum CFH concentrations and CFH/protein ratios were increased in samples from asthmatic patients, and correlated with loss of lung function, asthma control, severity and medication intensity, but not with plasma CFH concentrations. Sputum CFH/protein ratios were in positive correlation also with sputum eosinophilic cell counts in asthma. SC5b-9 concentrations were not higher in the asthmatic sputa, although they correlated with sputum CFH concentrations.

Conclusions

CFH level is elevated on asthmatic airway surface, and may be associated with uncontrolled inflammation in asthma.