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A correlation between K_I (equilibrium dissociation constants) and IC₅₀ (concentration at 50% inhibition) inhibitors for the family of blockers of the small conductance potassium ion channels and their intrinsic characteristics like molecular mass and volume have been investigated. Most of the blockers in the family are not selective, in contrast to apamin - an 18 amino acid bee venom toxin - that is known to be a highly potent and selective blocker of these channels. Differences and similarities between the blockers have been analyzed, pointing toward the origin of their selectivity and relative potency. In conclusion, an ion channel blocking is a process controlled mainly by diffusion, in accordance with previous experimental results.

Derivatives of N-substituted amides of α-piperazine-γ-hydroxybutyric acid display anticonvulsant activity. This study was performed on two representative compounds: N-benzylamide of α-(4-phenylpiperazine)-γ-hydroxybutyric acid (1) and N-benzylamide of α-(4-benzylpiperazine)-γ-hydroxybutyric acid (9). Comparison of the polycrystalline FT-Raman spectra, differing in spite of the similarity of these molecules enables indication of three regions with noteworthy differences in vibrations for CO, O–H, and phenyl rings, which are thought to form a pharmacophore. Visualization of the total charge density was found to be very useful for an insight into the strength of the bonds within the carbonyl and hydroxyl groups.

AbstractBackground:Previous studies have suggested that α-adducin (α-ADD) polymorphism may identify patients with a salt-sensitive form of hypertension. Aim:To investigate the association between Gly460Trp polymorphism of α-ADD and the pattern of blood pressure response to subacute (1 week) salt loading and depletion in young adult thin Polish hypertensives. Methods:The study group consisted of 44 subjects with salt-sensitive hypertension (SS) and 24 subjects with non-salt-sensitive hypertension (SR). Genomic DNA isolated from peripheral blood leukocytes was amplified by PCR method with primers flanking the polymorphic region. The mismatch near to 3′-end of the upstream primer was introduced to create a Nla IIIrestriction site in Trp 460 allele. In addition, excreted fraction of filtered sodium (FENa), plasma renin activity (PRA) and plasma concentrations of aldosterone (ALDO) were determined on normal, low and high salt diets. Results:FENa on normal or high salt diets were significantly lower in the SS hypertensives as compared with the SR patients. PRA in SS group was also significantly lower as compared with results in SR group, but only on high salt diet. No significant difference was detected in frequencies of genotypes and alleles of α-ADD gene between SS and SR subjects. An additional analysis with regard to genotype (Gly/Gly vs. Gly/Trp+Trp/Trp) showed no significant difference in changes of blood pressure as well as in results of laboratory investigations. Conclusion:Our results suggest lack of association between Gly460Trp polymorphism of α-adducin gene and salt sensitivity of blood pressure in Polish hypertensives.Copyright © 2001 S. Karger AG, Basel

The experimental and calculated IR and Raman spectra were compared and analyzed in the range of 1290–1440cm−1. The calculations were carried out with semi-empirical AM1 and PM3 parameterization and with Hartree–Fock approximation. The latter method reproduced the experimental spectra quite satisfactorily, while a model obtained with AM1 has got reasonably good frequencies and shows the vibrations in which quinuclidine nitrogen is involved. The calculations done with PM3 are completely inadequate in this respect, showing the weakness of this parameterization for compounds containing nitrogen atom.

An early event in atherogenesis is the adhesion of monocytes to endothelium via adhesion molecules such as VCAM-1 and intracellular adhesion molecule-1 (ICAM-1). It has been suggested that VCAM-1 plays a very important role in recruitment of monocytes in atherosclerosis. Several studies suggest that vitamin E has antiatherosclerotic properties. However, the mechanism of its antiatherogenic effect awaits elucidation. The aim of our study was to evaluate whether α-tocopherol can influence expression of endothelial cell adhesion molecules and endothelial adhesiveness. The study was performed on cultured human umbilical vein endothelial cells (HUVEC). HUVEC were pretreated with α-tocopherol (50 μmol/l) in different times before stimulation with TNFα (100 U/ml) or IL-1β (100 U/ml). Protein expression of VCAM-1 and ICAM-1 was measured by flow cytometry. mRNA expression of VCAM-1 was measured by reverse transcription polymerase chain reaction (RT-PCR). α-Tocopherol time dependently reduced agonist-induced VCAM-1 in both surface protein (about 40%, 48 h) and mRNA (about 35%, 48 h) expression in HUVEC but not ICAM-1 surface protein expression. Inhibitory effect of α-tocopherol was dependent on culture condition of HUVEC. Decreased VCAM-1 expression was associated with reduction (about 40%) of adherence between cytokine-stimulated HUVEC and peripheral blood mononuclear leukocytes (PBMC). Our results suggest that the antiatherogenic effect of α-tocopherol may in part be due to a downregulation of VCAM-1 expression.

Mouse lymphatic leukemia L1210 cells were characterized with polyclonal and monoclonal antibodies and lectins. The cells were found to have the phenotype IgG-, Thy-1.2-, Lyt-1-, Lyt-2-, asialo-GM-, TL-, I-Ad-, IL-2R+, peanut agglutinin+, and Helix pomatia lectin +/-. They retained expression of H-2Kd and H-2Dd. Thus, these cells resemble "null" cells.

The crystal structure of triglycine fluoberylate has been refined in the ferroelectric phase at a temperature of 23°C and in the paraelectric phase at 97°C using the data collected on a diffractometer CAD-4. Positions of all hydrogen atoms in both phases have been determined. The refinement of paraelectric phase in a space group without symmetry centre gives a good result in overcoming the difficulties resulting from the overlapping of atoms.

The scope of the paper is the simulation model of energy system expansion to which suitable decisions undertaken arbitrarily are introduced.

The synthesis, spectroscopic characteristics, and singlecrystal X‐ray structural analysis of quitenidine methyl ester monohydrate, a derivative of the muscarinic antagonist quinidine, are presented. Quitenidine methyl ester monohydrate (C20H24N2O4· H2O) crystallizes in the orthorhombic space group P212121, with a= 16.69(3) Å, b= 12.46(2) Å, c= 9.70(1) Å, and Z= 4. The crystal structure was refined to a discrepancy factor (R) of 0.097. Substitution of the quinidine vinyl chain with a carboxymethyl group does not influence the conformation. The carboxymethyl group is positionally disordered, a fact that complicates refinement of the structure. The water molecule is bonded to the quinuclidine nitrogen atom, and the hydroxyl group forms an intermolecular hydrogen bond with the quinoline nitrogen atom. The molecular structure of the ester was compared with those of quinidine, quinine, and four other antimuscarinic agents. An approximately linear relationship between the distance from the nonaromatic nitrogen to the plane of the aromatic part of the molecules and the blocking potency of these agents was noted; the greater this distance, the more potent is the antagonist.

The expression of plasma prekallikrein (PPK) mRNA has been investigated applying reverse transcription, followed by polymerase chain reaction, of mRNA (RT-PCR) in various human and rat tissues. PPK gene transcripts were detected in liver and kidney in both species and, in addition, in human adrenal gland and placenta. No PPK mRNA was identified in rat adrenal gland, heart, aorta, lung, brain cortex and medulla, hypothalamus, and uterus. These results show that PPK gene expression is not restricted to the liver.

The concentration of plasma prekallikrein (PK) in five patients with hepatocellular carcinoma (HCC) has been measured and related to levels in 18 patients with liver cirrhosis (LC) and 30 healthy subjects. It was found that the mean PK level was significantly increased in patients with HCC, while patients with LC demonstrated lower concentrations, as compared with healthy subjects. The results indicate that PK might be useful in screening cirrhotic patients for HCC. Longitudinal studies of PK in a larger group of patients at risk of developing HCC are therefore recommended.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

The article offers review on OPTIME solution from Schaeffler.

Hematopoietic stem and progenitor cells (HSPCs) tightly couple maintenance of the bone marrow (BM) reservoir, including undifferentiated long-term repopulating hematopoietic stem cells (LT-HSCs), with intensive daily production of mature leukocytes and blood replenishment. We found two daily peaks of BM HSPC activity that are initiated by onset of light and darkness providing this coupling. Both peaks follow transient elevation of BM norepinephrine and TNF secretion, which temporarily increase HSPC reactive oxygen species (ROS) levels. Light-induced norepinephrine and TNF secretion augments HSPC differentiation and increases vascular permeability to replenish the blood. In contrast, darkness-induced TNF increases melatonin secretion to drive renewal of HSPCs and LT-HSC potential through modulating surface CD150 and c-Kit expression, increasing COX-2/αSMA+macrophages, diminishing vascular permeability, and reducing HSPC ROS levels. These findings reveal that light- and darkness-induced daily bursts of norepinephrine, TNF, and melatonin within the BM are essential for synchronized mature blood cell production and HSPC pool repopulation.

Pathogenesis of several renal diseases is strongly connected with cytokines. The polymorphism of IL1RN gene exists in intron 2 and is caused by variable number of 86bp sequence repeats. In addition, previous studies confirmed the association of IL1RN*2 with inflammatory diseases, among them glomerulonephritis. Therefore it raises the question whether VNTR polymorphism of IL1RN gene determines the susceptibility to DMP and its clinical course.The study group consisted of 56 children with DMP and 105 healthy children as controls. Genomic DNA was extracted from peripheral blood leukocytes. The IL1RN intron 2 VNTR polymorphism was determined by PCR technique with primers flanking the polymorphic region. Significant differences in genotype (p=0,032) and allele (p=0,045) frequencies were observed between children with DMP and control group. The genotype distribution was as follows: *1/*1 - 48,2%, *1/*2 - 30,4%, *1/*3 - 3,6%, *2/*2 - 14,3%, *3/*3 - 1,8%, *3/*4 - 1,8% in DMP group and *1/*1 - 58,1%, *1/*2 - 36,2%, *1/*3 - 3,8%, *2/*2 - 1,9% in controls. The prevalence of alleles in children with DMP was: *1 - 65,2%, *2 - 29,4%, *3 - 4,5%, *4 - 1,9% while in control group: *1 - 78,1%, *2 - 20%, *3 -1,9%. Additionally IL1RN*2 allele homozygosity showed eight fold higher risk for DMP (OR=8,58; 95%CI, 1,73 to 42,48; p=0,008). No association between IL1RN genotypes and response to steroid therapy or frequency of relapses was observed in the study group.Our results suggest that IL1RN*2 homozygosity predisposes to diffuse mesangial proliferation in Polish children.

Aims. This paper describes the Heterodyne Instrument for the Far-Infrared (HIFI) that was launched onboard ESA's HerschelSpace Observatory in May 2009. Methods. The instrument is a set of 7 heterodyne receivers that are electronically tuneable, covering 480–1250 GHz with SIS mixers and the 1410–1910 GHz range with hot electron bolometer (HEB) mixers. The local oscillator (LO) subsystem comprises a Ka-band synthesizer followed by 14 chains of frequency multipliers and 2 chains for each frequency band. A pair of auto-correlators and a pair of acousto-optical spectrometers process the two IF signals from the dual-polarization, single-pixel front-ends to provide instantaneous frequency coverage of 2 × 4 GHz, with a set of resolutions (125 kHz to 1 MHz) that are better than 0.1 km s-1.Results. After a successful qualification and a pre-launch TB/TV test program, the flight instrument is now in-orbit and completed successfully the commissioning and performance verification phase. The in-orbit performance of the receivers matches the pre-launch sensitivities. We also report on the in-orbit performance of the receivers and some first results of HIFI's operations.

Aims. “Water In Star-forming regions with Herschel” (WISH) is a Herschelkey programme aimed at understanding the physical and chemical structure of young stellar objects (YSOs) with a focus on water and related species.Methods. The low-mass protostar HH 46 was observed with the Photodetector Array Camera and Spectrometer (PACS) on the HerschelSpace Observatory to measure emission in H2O, CO, OH, [O i], and [C ii] lines located between 63 and 186 μm. The excitation and spatial distribution of emission can disentangle the different heating mechanisms of YSOs, with better spatial resolution and sensitivity than previously possible.Results. Far-IR line emission is detected at the position of the protostar and along the outflow axis. The OH emission is concentrated at the central position, CO emission is bright at the central position and along the outflow, and H2O emission is concentrated in the outflow. In addition, [O i] emission is seen in low-velocity gas, assumed to be related to the envelope, and is also seen shifted up to 170 km s-1in both the red- and blue-shifted jets. Envelope models are constructed based on previous observational constraints. They indicate that passive heating of a spherical envelope by the protostellar luminosity cannot explain the high-excitation molecular gas detected with PACS, including CO lines with upper levels at >2500 K above the ground state. Instead, warm CO and H2O emission is probably produced in the walls of an outflow-carved cavity in the envelope, which are heated by UV photons and non-dissociative C-type shocks. The bright OH and [O i] emission is attributed to J-type shocks in dense gas close to the protostar. In the scenario described here, the combined cooling by far-IR lines within the central spatial pixel is estimated to be 2 × 10-2$L_\odot$, with 60–80% attributed to J- and C-type shocks produced by interactions between the jet and the envelope.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The expression of mRNA for inducible nitric oxide synthase (iNOS) in rat epithelial cells of epididymis was investigated with reverse transcription followed by polymerase chain reaction. Immunocytochemical reaction for iNOS was performed to confirm the enzyme’ s localization in the epididymal epithelium. Additionally, an indirect spectrophotometric method for nitric oxide (NO) determination was applied for measurement of nitrite production by cultured epididymal epithelial cells. Inducible NOS mRNA was detected in freshly isolated epithelial cells, in cultured cells without stimulation as well as in cultured cells after stimulation by lipopolysaccharide and interferon-gamma. Inducible NOS immunoreactivity was observed in the apical part of epithelial cells of epididymal sections and in the cytoplasm of cells in culture. Release of nitrite was observedin vitro in both the unstimulated and stimulated cells of caput (1·44 ± 0·94 v. 4·37 ± 2·42 µM) and cauda (0·69 ± 1·21 v. 5·21 ± 2·76 µM) epididymis (P < 0·001). To the best of our knowledge, this is the first study to demonstrate iNOS in the epididymal epithelial cells of the rat. Nitric oxide released by epididymal epithelial cells may act on cells and tissues located nearby. The results may help explain epididymal function: sperm storage, passage and maturation. Excessive epididymal NO production may also play a role in the inflammatory infertility of the male. Extra keyword: iNOS

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The absolute configuration of the phenylethylamide (I) is determined by X‐ray structure analysis (space group P21, Z=4).