Inhibition of 125I-labeled ristocetin binding to Micrococcus luteus cells by the peptides related to bacterial cell wall mucopeptide precursors: quantitative structure-activity relationships

Quantitative structure-activity relationships (QSAR) of N-Ac amino acids, N-Ac dipeptides, and N-Ac tripeptides in inhibition of 125I-labeled ristocetin binding to Micrococcus luteus cell wall have been developed to probe the details of the binding between ristocetin and N-acetylated peptides. The correlation equations indicate that (1) the binding is stronger for peptides in which the side chain of the C-terminal amino acid has a large molar refractivity (MR) value, (2) the binding is weaker for peptides with polar than for those with nonpolar C-terminal side chains, (3) the N-terminal amino acid in N-Ac dipeptides contributes 12 times that of the C-terminal amino acid to binding affinity, and (4) the interactions between ristocetin and the N-terminal amino acid of N-acetyl tripeptides appear to be much weaker than those with the first two amino acids.     

Methanol poisoning: a review and case study of four patients from Central Australia

Methanol intoxication, a rare and potentially lethal form of poisoning, usually results from ingestion and occasionally inhalation of methanol. Initial symptoms of blurred vision, elongated anion gap and metabolic acidosis are typically delayed and may not at first be recognised as methanol-related complaints. Once diagnosed, treatment must be prompt and definitive. As well as general supportive care, ethanol infusion, dialysis and alkalinization form the mainstays of treatment.

The cases described in this paper are compared to previous reports from other countries worldwide and contrast the variance in outcome often seen in methanol poisoning. The paper describes two tragic deaths and two lucky survivors, all of whom had consumed a cocktail of methanol and other alcoholic beverages at the same party.

The ICU nurse's role in managing the methanol-intoxicated patient relies on that person's sound knowledge of the unusual biochemical reactions occurring in the body and the need to institute definitive and supportive measures to help both patient and family recover.     

Trichinella infection and clinical disease

Trichinellosis is caused by ingestion of insufficiently cooked meat contaminated with infective larvae of <it>Trichinella</it> species. The clinical course is highly variable, ranging from no apparent infection to severe and even fatal disease. We report two illustrative cases of trichinellosis. Returning to Denmark a few days after having eaten roasted pork in the Republic of Serbia, a female patient suffered from severe vomiting, epigastric pain, diarrhoea, and later myalgia, generalized oedema, and prostration. A biopsy showed heavy infestation with <it>Trichinella spiralis</it>, 2000 larvae/g of muscle. Life-threatening cardiopulmonary, renal and central nervous system complications developed. The patient recovered after several months. Her husband, who also ate the pork, did not have clinical symptoms, but an increased eosinophil count and a single larva in a muscle biopsy confirmed infection. The epidemiology, clinical manifestations, diagnosis, treatment and prevention of trichinellosis are reviewed.      

A novel nonpeptide antagonist of the kinin B1 receptor: effects at the rabbit receptor

The kinin B1 receptor (B1R) has attracted interest as a potential therapeutic target because this inducible G protein-coupled receptor is involved in sustained inflammation and inflammatory pain production. Compound 11 (2-[(2R)-1-[(3,4-dichlorophenyl) sulfonyl]-3-oxo-1,2,3,4-tetrahydroquinoxalin-2-yl]-N-[2-[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]ethyl]acetamide) is a high-affinity nonpeptide antagonist for the human B1R, but it is potent at the rabbit B1R as well: its Ki value for the inhibition of [3H]Lys-des-Arg9-BK (bradykinin) binding to a novel myc-labeled rabbit B1R expressed in COS-1 is 22 pM. In contractility tests (organ bath pharmacology), we found that compound 11 is an apparently surmountable antagonist of des-Arg9-BK- or Lys-des-Arg9-BK-induced contraction of the rabbit isolated aorta (pA2 values of 10.6+/-0.14 and 10.4+/-0.12, respectively). It did not influence contractions induced by angiotensin II in the rabbit aorta or by BK or histamine in the jugular vein, but it suppressed the prostaglandin-mediated relaxant effect of des-Arg9-BK on the rabbit isolated mesenteric artery. Compound 11 (1 nM) inhibited both the phosphorylation of the extracellular signal-regulated kinase1/2 mitogen-activated protein kinases induced by Lys-des-Arg9-BK in serum-starved rabbit aortic smooth muscle cells and the agonist-induced translocation of the fusion protein B1R-yellow fluorescent protein expressed in human embryonic kidney (HEK) 293 cells. Compound 11 does not importantly modify the expression of myc-B1R over 24 h in HEK 293 cells (no detectable action as "pharmacological chaperone"). The present results support that compound 11 is a potent and highly selective antagonist suitable for further investigations of the role of the kinin B1R in models of inflammation, pain, and sepsis based on the rabbit.