Patient blood management: A solution for South Africa.

For more than 70 years the default therapy for anaemia and blood loss was mostly transfusion. Accumulating evidence demonstrates a significant dose-dependent relationship between transfusion and adverse outcomes. This and other transfusion-related challenges led the way to a new paradigm. Patient blood management (PBM) is the application of evidence-based practices to optimise patient outcomes by managing and preserving the patient's own blood. 'Real-world' studies have shown that PBM improves patient outcomes and saves money. The prevalence of anaemia in adult South Africans is 31% in females and 17% in males. Improving the management of anaemia will firstly improve public health, secondly relieve the pressure on the blood supply, and thirdly improve the productivity of the nation's workforce. While high-income countries are increasingly implementing PBM, many middle- and low-income countries are still trying to upscale their transfusion services. The implementation of PBM will improve South Africa's health status while saving costs.

Structure elucidation of 11-amino-8-hydroxypentacyclo[5.4.0.0(2, 6).0(3, 10).0(5, 9)]undecane-8,11-lactam through selective acetylation and complete 1H and 13C NMR spectral assignment of the mono-, di- and triacetates.

NMR techniques cannot unambiguously distinguish between 11-amino-8-hydroxypentacyclo[5.4.0.0(2, 6).0(3, 10).0(5, 9)]undecane-8,11-lactam and 8-amino-11-hydroxypentacyclo[5.4.0.0(2, 6).0(3, 10).0(5, 9)]undecane-8,11-lactam, both of which are possible products during the reaction of pentacyclo[5.4.0.0(2, 6).0(3, 10).0(5, 9)]undecane-8,11-dione with Strecker reagents. Treatment of 11-amino-8-hydroxy-pentacyclo[5.4.0.0(2, 6).0(3, 10).0(5, 9)]undecane-8,11-lactam with acetic anhydride at room temperature produced a monoacetate. With acetic anhydride containing sodium acetate, a triacetate was obtained at reflux temperature. Treatment with acetyl chloride and N,N-dimethylaniline produced a diacetate. High-field 1H and 13C NMR techniques were used in the structure elucidation and assignment of the different NMR resonances of these three acetylated compounds.

Structures of a tetradentate ferrocenyl ligand and its oxorhenium(V) complex in solution and in the solid state.

The novel ferrocenyl ligand rac-1,6-diferrocenyl-N,N'-bis(2-hydroxypropyl)-2,5-diazahexane (1, H(2)L) was synthesized from ferrocenylcarboxaldehyde and ethylenediamine followed by the reduction of the Schiff base with LiAlH(4) and subsequent N-alkylation with 1,2-propyleneoxide. The dianion of H(2)L reacted with [ReO(PPh(3))(2)Cl(3)], and the product was treated with NH(4)PF(6) to afford the complex [ReO(L-N(2)O(2))PPh(3)]PF(6) (2). Both the ferrocenyl ligand and the complex were characterized in solution by NMR spectroscopy and in the solid state by single-crystal X-ray diffraction studies. NMR investigations reveal two solvent-dependent isomers for the ferrocenyl ligand in solution of which the major form is the more ordered one. The cation of 2 displays a nonsymmetrically coordinated N(2)O(2) ligand.

Experimental studies and potential-energy calculations of the blocked tetrapeptide Ac-Lys-Gln-Gly-Ile-NMA from the third loop of a short-chain snake venom neurotoxin.

The conformational space of the tetrapeptide Ac-Lys-Gln-Gly-Ile-NMA from the beta-bend in the third loop of a short-chain snake venom neurotoxin was investigated with the aid of energy calculations. It was shown that this peptide has a preference for an alpha-helical conformation. This result was compared with the experimentally determined conformations, as observed using NMR and CD spectroscopy. With NMR spectroscopy a random-coil conformation of the peptide is indicated in H2O, DMSO and TFE. The results from the CD experiments suggest that the peptide exists as a random coil in water, but a small population of alpha-helical conformations is present in TFE. These results indicate that additional long-range interactions also play a role in the conformation of this tetrapeptide in the protein.

Experimental studies and potential energy calculations of the blocked tetrapeptide Ac-Lys-Pro-Gly-Ile-NMA from the third loop of short-chain snake venom neurotoxins.

The conformational space of the tetrapeptide Ac-Lys-Pro-Gly-Ile-NMA from the beta-bend present in the third loop of short-chain snake venom neurotoxins was investigated with the aid of energy calculations, resulting in the identification of an ensemble of beta-turn conformations. These results were compared with the experimentally determined conformations, as observed using NMR and CD spectroscopy. A random coil conformation of the peptide is indicated in polar hydrogen-bonding solvents. In less polar solvents the peptide backbone assumed a more rigid conformation, as reflected by the existence of at least a type II beta-turn conformation.

Conformational analysis of mu-selective [D-Ala2,MePhe4]enkephalins.

The conformational space of the potent mu-selective opioids [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO) and [D-Ala2,MePhe4,Met(O)-ol5]enkephalin (FK 33-824) has been analyzed by 1H-NMR spectroscopy and theoretical calculations involving systematic conformational searching and energy minimizations. A cis-trans equilibrium of the Gly3-MePhe4 amide bond is induced by the N-methyl group, and the more energetically favoured trans isomer is proposed as the biologically relevant form. A compact interaction between the side chains of Tyr1 and D-Ala2 was demonstrated by NOE and ROE effects in both peptides in D2O and DMSO-d6, further supported by shielding of the D-Ala2 methyl protons in both solvents. Analysis of coupling constants, NOE and ROE data indicated significant restriction of the conformational freedom of the MePhe4 side-chain for both peptides in the two solvents. The NMR results and theoretical calculations point towards folded low energy conformations characterized by a beta II-type turn around Gly3-MePhe4. For the trans isomer, a Tyr1-MePhe4 phenyl ring separation between 8.5 and 12.5 A was accompanied by proximity between the D-Ala2 side chain and the C-terminal in low energy conformations. The results are in good agreement with available data on related active enkephalins. The conformational effects induced by simultaneous incorporation of D-Ala2 and MePhe4 in enkephalins is discussed in the light of the enhanced mu-opioid receptor selectivity and activity of these peptides.

High-resolution solid-state carbon-13 nuclear magnetic resonance spectra of mofebutazone, phenylbutazone, and oxyphenbutazone in relation to X-ray crystallographic data.

The solid-state 13C NMR spectra of mofebutazone, phenylbutazone, and oxyphenbutazone monohydrate and anhydrate are presented. The crystal structures of these pyrazolidinedione derivatives, obtained by single-crystal X-ray analysis, were previously reported, revealing distinct differences in crystal structure. In this report, the chemical shift values observed for the solid-state 13C spectra are related to the chemical environment of the various carbon atoms and compared with the crystallographic data. Results indicate that solid-state NMR spectroscopy is potentially useful in the study of drugs in the solid state.

The extended promoter of the gene encoding ribosomal protein S33 in yeast consists of multiple protein binding elements.

At least 4 different, protein binding cis-acting elements are present in the upstream region of the S33-gene. The major protein binding site is situated between positions -148 and -163 relative to the ATG start codon. It binds a trans-acting factor designated SUF (S33 Upstream Factor). When yeast cells are growing on glucose, deletion of this site results in a decrease of transcription of 50%. Using ethanol as a carbon-source, deletion of the SUF-responsive site lowers the transcription as much as 80%. A second protein binding site is found between positions -85 and -105. Only extracts from glucose-grown cells contain a factor that is able to bind to this site in vitro. A third protein binding site was found using a protein extract from ethanol-grown cells. This site, which is located quite close to the transcriptional start site, is probably responsible for the 20% residual transcription when the SUF binding site is removed. Finally, a site far upstream was found, which binds a protein from both glucose-grown and ethanol-grown cells. This site may function as an upstream repression site which is only functional when a non-fermentable carbon-source is used. Taking these findings into account, we present a model for the carbon-source dependent transcription activation of the gene encoding S33.

Degradation of trimethoprim.

Trimethoprim undergoes thermally and photochemically catalyzed hydrolysis or oxidation to give rise to at least five products. The structures of these compounds were determined by physical methods and it was found that the resonance of C-5 in the 13C NMR spectrum is indicative of the substitution pattern of the resultant amino hydroxy pyrimidines.

Detection of 3-hydroxy-3-methyloxindole in human urine.

During routine toxicological screening of urine for possible drug overdose, using two-dimensional thin-layer chromatography, an unknown substance was periodically detected that could not be related to any known drug. The substance was mass-isolated from the urine of a schizophrenic patient, who excreted it prolifically and it was chemically identified as 3-hydroxy-3-methyloxindole by mass spectrometry and 1H- and 13C-NMR. The structure was confirmed by synthesis through methylation of isatin. This is the first report associating 3-hydroxy-3-methyloxindole with human biochemistry. It is thought that this substance is an in vivo oxidation product of 3-methylindole which is a metabolic product of tryptophan, produced by bacteria in the colon.

Configuration assignments of the amino acid residues and the presence of N-methyldehydroalanine in toxins from the blue-green alga, Microcystis aeruginosa.

The configuration assignment of the alpha-carbon atom of amino acid residues in four toxin variants from Microcystis aeruginosa have been made by stereospecific enzymic transformations. The relative conformation assignment of the beta-carbon atom of beta-CH3-aspartic acid could be made by comparison of the electrophoretic mobility with literature values reported for the authentic compound. The presence of an N-methyldehydroalanine residue, which, due to elimination of methylamine under hydrolytic conditions, previously escaped detection by conventional means, has been confirmed by identification of N-methylalanine in the hydrolysate after reduction of toxin with sodium borohydride.

Further compounds from the pedal gland of the bontebok (Damaliscus dorcas dorcas).

The identification of four further major constituents of the pedal gland exudate of the bontebok, Damaliscus dorcas dorcas, viz. alpha-terpineol, 2-n-heptylpyridine, m-cresol and (A)-6-dodecen-4-olide and the investigation of the stereochemistry of the double bond in (Z)-6-dodecen-4-olide by means of iterative computer analysis are described. An improved synthesis of this compound is outlined.