Poly(oxyethylene)s terminated at both ends with phosphonium ion end groups, 2. Properties

Poly(oxyethylene)s with number-average degrees of polymerization (DP_n) ranging from ≈ 6 to ≈ 80, terminated at both ends with phosphonium ion end groups (diionic poly-EO), have been prepared and characterized as described in the preceding paper. Viscosities of diionic poly-EO were measured, both in solution and in bulk. In chloroform solution, at low concentration (< 1 g/100 mL), the viscosity of diionic poly-EO was lower than the viscosity of nonionic (terminated with HO-groups) poly-EO of the same DP_n. At higher concentrations, the viscosity of diionic poly-EO exceeded that of nonionic poly-EO and increased sharply with increasing concentration. At the constant weight concentration of ≈4 g/100 mL, the viscosities of short-chain diionic poly-EO were higher and those of longer chain diionic poly-EO were lower than the viscosities of the nonionic poly-EO of the same chain lengths. These results were attributed to a predominant intramolecular aggregation of terminal ionic groups at low concentration of ionic groups in solution and predominant intermolecular aggregation at higher concentration of ionic groups. The results of bulk viscosity measurements as well as the results of differential scanning calorimetry measurements of the dependence of the glass transition temperature on the DP_n of diionic poly-EO indicated that in bulk physically cross-linked networks were formed, due to intermolecular aggregation of terminal ionic groups.     

Exome sequencing reveals a novel COL2A1 mutation implicated in multiple epiphyseal dysplasia

Mutations in the COMP, COL9A1, COL9A2, COL9A3, MATN3, and SLC26A2 genes cause approximately 70% of multiple epiphyseal dysplasia (MED) cases. The genetic changes involved in the etiology of the remaining cases are still unknown, suggesting that other genes contribute to MED development. Our goal was to identify a mutation causing an autosomal dominant form of MED in a large multigenerational family. Initially, we excluded all genes known to be associated with autosomal dominant MED by using microsatellite and SNP markers. Follow‐up with whole‐exome sequencing analysis revealed a mutation c.2032G>A (p.Gly678Arg) in the COL2A1 gene (NCBI Reference Sequence: NM_001844.4), which co‐segregated with the disease phenotype in this family, manifested by severe hip dysplasia and osteoarthritis. One of the affected family members had a double‐layered patella, which is frequently seen in patients with autosomal recessive MED caused by DTDST mutations and sporadically in the dominant form of MED caused by COL9A2 defect.     

Involvement of nitric oxide in angiogenic activities of vascular endothelial growth factor isoforms

We compared effects of vascular endothelial growth factor-121 (VEGF121) and vascular endothelial growth factor-165 (VEGF165) on generation of NO in HUVEC and the involvement of NO in VEGF121- and VEGF165-induced angiogenesis. VEGF stimulated synthesis of NO within seconds, reaching peak concentrations of 450 +/- 25 and 180 +/- 15 nmol/l for VEGF121, and VEGF165, respectively. The VEGF121 increased NO production for about 40 s while VEGF165-stimulated NO release lasted only for about 20 s. Accordingly, cGMP elevation was stronger in VEGF121- than in VEGF165-treated cells. The VEGF121 was a very weak mitogen but strong chemoattractant for HUVEC, whereas VEGF165 potently induced both cell proliferation and migration. NO appeared to be involved in the endothelial migration and morphogenesis but not in the proliferation. NO was also a permissive molecule for VEGF121- but not for VEGF165-induced capillary sprouting in spheroid culture. In conclusion, VEGF121 is a stronger stimulator of endothelial nitric oxide synthase (eNOS) activity, and angiogenic potential of VEGF121 is more reliant on NO contribution.     

Cerebral protection by AMPA- and NMDA-receptor antagonists administered after severe insulin-induced hypoglycemia

Summary Excitatory amino acids are implicated in the development of neuronal cell damage following periods of reversible cerebral ischemia or insulin-induced hypoglycemic coma. To explore the importance of glutamate receptor activation in the posthypoglycemic phase, we exposed rats to 20 min of insulin-induced severe hypoglycemia. The rats were treated immediately after the hypoglycemic insult with four regimes of glutamate receptor antagonists: (1) the AMPA (-amino-3-hydroxy-5-methyl-4-isoxazole propriate)-receptor antagonist NBQX [2.3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline] given as a bolus dose of 30 mg · kg^-1 i.p., followed by an i.v. infusion of 225 g · kg^-1 · min^-1 for 6 h; (2) the non-competitive NMDA-receptor antagonist, dizocilpine (MK-801) 1 mg · kg^-1 given i.v.; (3) a combined NBQX treatment, (a bolus dose of 10 mg · kg^-1 i.p., followed by an i.v. infusion of 225 g · kg^-1 · min^-1 for 6 h), with dizocilpine 0.33 mg · kg^-1 given twice i.p. at 0 and 15 min after recovery and (4) the competitive NMDA-receptor blocker CGP 40116 [D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid] 10 mg · kg^-1 given i.p.. In the striatum, all glutamate receptor blockers significantly decreased neuronal damage by approximately 30%. An approximately 50% decrease in neuronal damage was demonstrated in neocortex and hippocampus following the combined treatment with NBQX and dizocilpine, while protection was variable following the treatment with a single glutamate-receptor antagonist. We conclude that neuronal damage continues to develop in the striatum and in cortical brain regions in the posthypoglycemic period and that both NMDA- and AMPA-receptors contribute to this process, possibly by a change in the cellular response to both AMPA- and NMDA-receptor stimulation.     

Efficiency of adjuvant immunochemotherapy following curative resection in patients with locally advanced gastric cancer

Background Despite curative resection, 50%–90% of gastric cancer patients die of disease relapse. Although some clinical trials have indicated that chemotherapy and immunochemotherapy may be effective modalities, more recent studies have not been able to define the standard treatment for advanced gastric cancer. The present study evaluated the effect of adjuvant immunochemotherapy with the use of BCG (bacille Calmette-Guérin) and FAM (5-fluorouracil, adriamycin, mitomycin C) chemotherapy on the survival of patients with locally advanced resectable gastric cancer.Methods A total of 156 patients with stage III or IV gastric cancer who had undergone curative resection were randomly assigned to three treatment groups: BCG + FAM (immunochemotherapy), FAM (chemotherapy), and control (surgery only). Treatment was continued for 2 years or until death. Further postsurgical follow up was carried on for up to 10 years.Results Overall 10-year survival was 47.1% for the immunochemotherapy group (P < 0.037 vs FAM and P < 0.0006 vs control), 30% for the chemotherapy group (vs control, NS), and 15.2% for the control group. In patients with pT2/T3 primary tumors, 10-year survival was 55.3% for BCG + FAM vs 28.2% for FAM (P < 0.01) and 14.6% for the control group (P < 0.00018). BCG + FAM signifi-cantly improved the survival of patients with intestinal-type but not diffuse-type cancer. Immunochemotherapy was well tolerated.Conclusion This study, based on a limited number of patients, indicates that adjuvant immunochemotherapy (BCG + FAM) may prolong the survival of gastric cancer patients after curative gastrectomy; in particular, in patients with pT2/T3 tumors and intestinal-type primary tumors. There was no survival benefit from FAM adjuvant chemotherapy.     

Jansen type of spondylometaphyseal dysplasia

Metaphyseal dysplasia, type Jansen (JMD), is a rare skeletal dysplasia with characteristic radiographic abnormalities. Of the various types of metaphyseal dysplasia, JMD shows the most severe alteration in metaphyseal architecture. All of the long tubular bones, including those of the hands and feet, show metaphyseal irregularity with a fragmented appearance and slight widening. The adjacent physes are abnormally widened, while the epiphyses tend to be slightly enlarged, rounded but otherwise normal. The spine in infancy and childhood usually appears normal. This report describes a young girl with metaphyseal changes typical of JMD except for the hands and feet, which appeared normal. She also showed very unusual abnormalities of the spine. This appears, therefore, to represent a unique osteochondrodysplasia for which we propose the term spondylometaphyseal dysplasia, type Jansen. Received: 4 April 1999 Revision requested: 6 April 1999 Revision received: 29 November 1999 Accepted: 1 December 1999     

Using the Smith-Watson-Topper Parameter and Its Modifications to Calculate the Fatigue Life of Metals: The State-of-the-Art

The Smith-Watson-Topper parameter (SWT) in its original form was designed to estimate the fatigue life of metal materials in a uniaxial load state (tension–compression) in the range up to fatigue crack initiation, with non-zero mean values. This parameter is based on the analysis of both stress and strain. Therefore, the stress–strain criterion is the focus, rather than the energy criterion. This paper presents the original SWT model and its numerous modifications. The first part presents different versions of this parameter defined by the normal parameters. Then, it presents versions defined through the tangent parameter and the most promising parameter defined through the tangent and normal parameters. It was noted that the final form of the equivalent value is defined either by stress or by an energy parameter. Therefore, the possible characteristics from which the fatigue life can be determined are also presented.     

Strong antioxidant activity of carane derivatives

Oxidants play a significant role in causing oxidative stress, which underlies the pathogenesis of inflammation and rheumatoid arthritis. The processes associated with inflammatory responses are complex and often involve reactive oxygen species. There are many mediators that initiate and amplify the inflammatory response such as histamine, serotonin and metabolic products of arachidonic acid (thromboxane, prostaglandins and leukotrienes). In the present study, we examined the antioxidant activity of carane derivatives – KP-23 and its optical isomers – that possess strong local anesthetic and anti-inflammatory activity. The antioxidant effects (expressed as Trolox Equivalent Antioxidants Capacity, TEAC) were observed for one of the optical isomers of carane, a derivative of propranolol – KP-23R. The relative scavenging effect (%R) of ABTS⁺ by KP-23S, KP-23R and standards measured at 30 min was the following, listed in decreasing order: tetracaine > KP-23S > KP-23R > procaine > lignocaine > benzocaine (99, 85, 80, 38, 21 and 20%, respectively, at a concentration of 10 mM). The IC₅₀ values also show strong antioxidant properties of the investigated KP compounds (ranging between 11–18 mM) and tetracaine (6.2 mM) compared to other local anesthetics (129–348 mM). Moreover, monoterpene derivatives were more effective as antioxidants than propranolol diastereoisomers (280–528 mM). We found that carane derivatives, in contrast to propranolol diastereoisomers, serve as potent antioxidants by scavenging radicals     

Permeability and Load Capacity of Iron Porous Bearings with the Addition of Hexagonal Boron Nitride

Due to their properties, porous sliding bearings are considered to be maintenance-free, which means that no lubrication is required during operation. Their design enables operation at low rotational speeds with high load. Another effect of this bearing design is the lubrication continuity in the tribological pair. In this study, the selected tribological properties (such as load capacity and permeability) of new-generation iron porous bearings with boron nitride powder were experimentally investigated. Tests were carried out under various conditions, using unique test apparatus. The addition of 3% (weight) of hexagonal boron nitride (hBN) significantly increased the load capacity of tested porous bearings in comparison to the same standard bearings containing 2.5% copper. The obtained p_gr·v rating reached almost 7 MPa, which is a value almost three times higher than the requirements for this type of bearing. It is worth emphasizing that such a result was obtained despite a noticeable deterioration in the air and oil permeability of the bearing.