Prostaglandin I2 reduces activation of human arterial smooth muscle cells in-vivo

Patients suffering from peripheral vascular disease have been "ultima ratio"-treated with PGI2 at a rate of 5 ng/kg/min for 6 hours a day and 5 consecutive days i.v. 20 of them underwent surgery thereafter as therapy was not sufficient. A histological examination and quantification of vascular tissue revealed that the number of activated smooth muscle cells was significantly lower in treated patients vascular segments than in untreated ones in all the different age groups. A comparable suppression was found in the intima and the media as well. It is thus concluded, that PGI2 inhibits smooth muscle cell proliferation most probably by inhibiting PDGF-release from the platelets and stimulation of smooth muscle cell cAMP. To achieve a more beneficial PGI2-effect at the vascular level, a prolonged PGI2-therapy looks rather promising.     

Prostaglandin 12 reduces activation of human arterial smooth muscle cells in-vivo

Patients suffering from peripheral vascular disease have been “ultima ratio”-treated with PGI2 at a rate of 5 ng/kg/min for 6 hours a day and 5 consecutive days i.v. 20 of them underwent surgery thereafter as therapy was not sufficient. A histological examination and quantification of vascular tissue revealed that the number of activated smooth muscle cells was significantly lower in treated patients vascular segments than in untreated ones in all the different age groups. A comparable suppression was found in the intima and the media as well. It is thus concluded, that PGI2 inhibits smooth muscle cell proliferation most probably by inhibiting PDGF-release from the platelets and stimulation of smooth muscle cell cAMP. To achieve a more beneficial PGI2-effect at the vascular level, a prolonged PGI2-therapy looks rather promising.     

Volatile Organic Compounds in Uremia

Background

Although “uremic fetor” has long been felt to be diagnostic of renal failure, the compounds exhaled in uremia remain largely unknown so far. The present work investigates whether breath analysis by ion mobility spectrometry can be used for the identification of volatile organic compounds retained in uremia.

Methods

Breath analysis was performed in 28 adults with an eGFR ≥60 ml/min per 1.73 m², 26 adults with chronic renal failure corresponding to an eGFR of 10–59 ml/min per 1.73 m², and 28 adults with end-stage renal disease (ESRD) before and after a hemodialysis session. Breath analysis was performed by ion mobility spectrometryafter gas-chromatographic preseparation. Identification of the compounds of interest was performed by thermal desorption gas chromatography/mass spectrometry.

Results

Breath analyses revealed significant differences in the spectra of patients with and without renal failure. Thirteen compounds were chosen for further evaluation. Some compounds including hydroxyacetone, 3-hydroxy-2-butanone and ammonia accumulated with decreasing renal function and were eliminated by dialysis. The concentrations of these compounds allowed a significant differentiation between healthy, chronic renal failure with an eGFR of 10–59 ml/min, and ESRD (p<0.05 each). Other compounds including 4-heptanal, 4-heptanone, and 2-heptanone preferentially or exclusively occurred in patients undergoing hemodialysis.

Conclusion

Impairment of renal function induces a characteristic fingerprint of volatile compounds in the breath. The technique of ion mobility spectrometry can be used for the identification of lipophilic uremic retention molecules.     

15N, 13C and 1H resonance assignments and secondary structure determination of a variable heavy domain of a heavy chain antibody

Heavy chain antibodies differ in structure to conventional antibodies lacking both the light chain and the first heavy chain constant domain (CH1). Characteristics of the antigen-binding variable heavy domain of the heavy chain antibody (VHH) including the smaller size, high solubility and stability make them an attractive alternative to more traditional antibody fragments for detailed NMR-based structural analysis. Here we report essentially complete backbone and side chain ¹⁵N, ¹³C and ¹H assignments for a free VHH. Analysis of the backbone chemical shift data obtained indicates that the VHH is comprised predominantly of β-sheets corresponding to nearly 60 % of the protein backbone.     

Molecular characterization of β-thalassemia in Czechoslovakia

Summary We have identified different -thalassemia mutations in 93 members of 34 families of Czech or Slovakian descent using gene amplification, hybridization with specific ³²P-labeled oligonucleotide probes, sequencing of amplified DNA, and gene mapping. The GA mutation at IVS-I-1 was found in 18 families; other Mediterranean mutations were IVS-II-1 (GA), IVS-II-745 (CG), IVS-I-110 (GA), and codon 39 (CT); these were present in 9 additional families. The GT mutation at codon 121, known to cause Heinzbody -thalassemia, was present in 3 families, and the frameshift at codons 82/83 (-G), first described in the Azerbaijanian population, in 2 families. A newly discovered allele was a frameshift at codons 38/39 (-C). One -thalassemia allele was incompletely characterized. We observed in 2 families a TC mutation at position +96 UTR (untranslated region) relative to the termination codon; this mutation likely is a rare polymorphism, -Thalassemia was rare; only one person carried the -^3.7 heterozygosity, and one other had a yet to be identified -thalassemia-1, while seven had the ^{anti 3.7} triplication.     

Vascular supply of the anterior interventricular epicardial nerves and ventricular Purkinje fibers in the porcine hearts

The aim of this study was to perform a pilot histological and quantitative analysis of the blood vessels accompanying the epicardial nerves (vasa nervorum) in the porcine hearts. Twenty healthy porcine hearts were used in this study. The blood vessels were analyzed by light microscopy using four different staining techniques in transverse sections taken from the upper, middle, and lower segments of the anterior part of the interventricular region and the adjacent parts of the right and left ventricles containing epicardial nerves and the endocardial peripheral parts of the Purkinje fibers. In total, 317 epicardial nerves were detected. The vasa nervorum were present in 75.7% of these nerves. The vasa nervorum resembled arterioles and postcapillary and collecting venules. One hundred and forty nine epicardial nerves were perivascular, located in the adventitia of the anterior interventricular artery and vein. The remaining 168 nerves ran freely through the epicardial interstitium. The presence of the vasa nervorum was not related to topographical location or nerve diameter. Additionally, from a total of 33 analyzed ventricular complexes of Purkinje fibers small blood vessels located in their proximity were identified in only two cases. It can be concluded that the majority of the anterior epicardial nerves of porcine heart possess well-developed vasa nervorum. In contrast, similar blood vessels are rarely present in the vicinity of the Purkinje fibers. The data obtained contribute to a better understanding of the nutrition of the cardiac nerves.     

Physiological effects of different types of beta-glucan

Background: Numerous types of glucans have been isolated from almost every species of yeast, grain, and fungi. These products have been extensively studied for their immunological and pharmacological effects. Aim: In this paper we evaluated the possibility whether individual glucans will be similarly active against each of the tested biological properties or if each glucan will affect different reactions. Methods: Immunological effects of glucans were measured by evaluation of phagocytosis of HEMA particles by peripheral blood leukocytes and production of IL-2 by mouse splenocytes. Next we measured the effects of long-term treatment with glucan on levels of blood glucose and blood cholesterol. Four different glucans differing in origin (yeast, grain and mushroom) were used. Results: Our results showed that the same glucan, yeast-derived insoluble #300 glucan, stimulated phagocytosis of peripheral blood leukocytes, production of IL-2 by mouse splenocytes, lowered the cholesterol levels in mice with experimentally-induced cholesterolemia and lowered the level of blood sugar after induced hyperglycaemie. The remainder of tested glucans were only marginally active. Conclusion: Taken together, our study showed that with respect to natural glucans, there is a yes-or-no effect suggesting that highly purified and highly active glucans will have pleiotropic impact, whereas poorly isolated and/or less active glucans will have only mediocre biological properties.