Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events

Recently, certain lots of heparin have been associated with an acute, rapid onset of serious side effects indicative of an allergic-type reaction. To identify potential causes for this sudden rise in side effects, we examined lots of heparin that correlated with adverse events using orthogonal high-resolution analytical techniques. Through detailed structural analysis, the contaminant was found to contain a disaccharide repeat unit of glucuronic acid linked beta1-->3 to a beta-N-acetylgalactosamine. The disaccharide unit has an unusual sulfation pattern and is sulfated at the 2-O and 3-O positions of the glucuronic acid as well as at the 4-O and 6-O positions of the galactosamine. Given the nature of this contaminant, traditional screening tests cannot differentiate between affected and unaffected lots. Our analysis suggests effective screening methods that can be used to determine whether or not heparin lots contain the contaminant reported here.     

Evaluation of sexual functions and sexual behaviors after penile brachytherapy in men treated for penile carcinoma

Purpose

To assess sexual functions and behaviors of men treated by penile brachytherapy for a cancer of the penis.

Materials and methods

Thirty eight men (19 patients treated by penile brachytherapy for a cancer of the penis and 19 age paired-matched controls) participated in a survey about sexuality. The mean age of patients and controls were 73.2 +/- 11.7 and 70.0 +/- 10.5 years, respectively (NS). Controls were men without penile pathology, without history of cancer and no evidence of cognitive impairment. All agreed to participate in the survey about sexuality using 2 questionnaires : the IIEF questionnaire, which explores 4 domains of sexual functions, namely erection, satisfaction, orgasm and desire, and a questionnaire created using the BASIC IDEA grid, which addresses nine domains: behavior, affect, sensation, self-image, cognition, interpersonal, drugs, expectation and attitude.

Results

Patients had better scores than controls in 3 domains of the IIEF: erection, desire and satisfaction. These results contrasted with the frequency of intercourse and the quality of erection (evaluated through the BASIC IDEA questionnaire) that were not significantly different between the two populations. Patients also had significantly higher frequency of masturbation (p <0.001) lower worry about sexual performance and higher expected satisfaction for future life (p: 0.021) than controls.

Conclusion

Penile brachytherapy is a treatment of cancer of the penis that seems to have a moderated impact on sexual functions since most of sexual scores are not inferior in these patients than in age pair-matched controls.

     

<Emphasis Type="Italic">N</Emphasis>-Methyl-<Emphasis Type="SmallCaps">d</Emphasis>-aspartate Receptor Antagonists Have Variable Affect in 3-Nitropropionic Acid Toxicity

There is accumulating evidence that excitotoxicity and oxidative stress resulting from excessive activation of glutamate (N-methyl-d-aspartate) NMDA receptors are major participants in striatal degeneration associated with 3-nitropropionic acid (3NP) administration. Although excitotoxic and oxidative mechanisms are implicated in 3NP toxicity, there are conflicting reports as to whether NMDA receptor antagonists attenuate or exacerbate the 3NP-induced neurodegeneration. In the present study, we investigated the involvement of NMDA receptors in striatal degeneration, protein oxidation and motor impairment following systemic 3NP administration. We examined whether NMDA receptor antagonists, memantine and ifenprodil, influence the neurotoxicity of 3NP. The development of striatal lesion and protein oxidation following 3NP administration is delayed by memantine but not affected by ifenprodil. However, in behavioral experiments, memantine failed to improve and ifenprodil exacerbated the motor deficits associated with 3NP toxicity. Together, these findings suggest caution in the application of NMDA receptor antagonists as a neuroprotective agent in neurodegenerative disorders associated with metabolic impairment.     

The Cu/Zn superoxide dismutase +35A/C (rs2234694) variant correlates with altered levels of protein carbonyls and glutathione and associates with severity of COPD in a Tunisian population

Chronic obstructive pulmonary disease (COPD) is a major cause of mortality that has been associated with inflammation and oxidative stress. The purpose of the present case–control study was to determine the relationships between oxidative stress-related genetic variants and the risk and severity of COPD, as well as, the influence of these variants on inflammatory and oxidative stress parameters. Genotyping of superoxide dismutase 1 (SOD1) + 35 A/C (rs2234694), catalase [A-21T (rs7943316), C-262T (rs1001179)] and glutathione peroxidase 1 (reduced glutathione (GSH)-Px1) 198Pro/Leu (rs1050450) was carried out in 143 patients with COPD and 216 healthy controls using PCR-RFLP. Serum levels of IL-6 and TNF-α were determined by enzyme-linked immunosorbent assays (ELISA), while the levels of reduced GSH, total antioxidant status (TAS), H₂O₂, lipid peroxides (TBARS) and protein carbonyls (PCs) were determined using spectrophotometric methods. We also evaluated the activities of GSH-Px, catalase, and superoxide dismutase (SOD) in both plasma and erythrocytes. We did not observe significant differences in the genotype and allele frequencies of chosen variants between COPD patients and healthy controls. A significant correlation was retrieved between the SOD1?+?35A/C variant and disease severity (odds ratios (OR) = 0.15, p?=?0.04). In addition, patients having the +35AC genotype presented increased plasma levels of GSH and a reduced level of PCs (p?=?0.03, p?=?0.04, respectively). The present data highlighted the important role of antioxidant enzymes and their genetic variants in the oxidative stress-mediated pathogenesis and progression of COPD.     

Effect of temperature variations on growth,reproduction, amino acid synthesis,fat and sugar content in ulva fasciata delile plants

This work deals with the effect of temperature variations on growth, reproduction, amino acid synthesis, fat and sugar content in Ulva fasciata in habiting the littoral region of the Mediterranean shore bordering Alexandria.Higher temperatures above 30°C have lethal effects on some parts of the algal fronds while the other parts are rather resistant. The latter are scattered groups of cells, which usually regenerate new plants when carried even to distant parts due to detrimental action of waves and currents. They serve a good means for vegetative propagation and spread better than zooids, which probably perish under such severe and violent conditions.The rate of growth of Ulva indicated by the increase in dry weight and total nitrogen, increases at rising temperature till the latter becomes limiting.Higher temperatures favour the growth and development of sporophytic phases, known by their deep green colouration, while temperatures below 20°C favour the production of gametophytes, identified by their yellowish green colour. This might explain why most of the algal crops of Ulva fasciata produced from parental stock (3 crops per year i.e. annually), are sporophytes.Moderate temperatures were favourable for growth, reproduction and the various metabolic processes. Amino acids and sugar contents increase with the rise of temperature, reaching their maximum around 25°C, while fat content increases at still lower temperatures.     

Survival of Alternaria cheiranthi in soil

Summary Experiments were conducted to study the survival of Alternaria cheiranthi in wet and dry soil. As free spores, survival was demonstrated only in air-dry soil. In wet soil, lysis of the germ tubes commenced after the second day. On wallflower seeds, the pathogen was viable until the seeds were decomposed. It was concluded that the fungus showed a low competitive saprophytic ability in the soil     

Design,synthesis, antimicrobial evaluation and molecular docking studies of some new 2,3-dihydrothiazoles and 4-thiazolidinones containing sulfisoxazole

Microbial resistance to the available drugs poses a serious threat in modern medicine. We report the design, synthesis and in vitro antimicrobial evaluation of new functionalized 2,3-dihydrothiazoles and 4-thiazolidinones tagged with sulfisoxazole moiety. Compound 8d was most active against Bacillis subtilis (MIC, 0.007?µg/mL). Moreover, compounds 7c–d and 8c displayed significant activities against B. subtilis and Streptococcus pneumoniae (MIC, 0.03–0.06?µg/mL and 0.06–0.12?µg/mL versus ampicillin 0.24?µg/mL and 0.12?µg/mL; respectively). Compounds 7a and 7c–d were highly potent against Escherichia coli (MIC, 0.49–0.98?µg/mL versus gentamycin 1.95?µg/mL). On the other hand, compounds 7e and 9c were fourfolds more active than amphotericin B against Syncephalastrum racemosum. Molecular docking studies showed that the synthesized compounds could act as inhibitors for the dihydropteroate synthase enzyme (DHPS). This study is a platform for the future design of more potent antimicrobial agents.