1,2-Dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) monolayers: influence of temperature, pH, ionic strength and binding of alkaline earth cations

Ion binding and lipid ionization of the acidic phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) in monolayers was studied by measuring the lateral pressure Pi as a function of the molecular area A at the air/water interface at different temperatures. The pH of the subphase (pH 2 and 7) and the ionic strength (NaCl) was varied. In addition, different divalent cations (1mM MgCl2, CaCl2 and SrCl2, pH 7) were added. DMPG is partly protonated on pure water at pH 7. An increase in the NaCl concentration in the subphase leads to film expansion. This effect is caused by an ionization of the headgroup of DMPG, i.e. a shift of the apparent pK. More condensed films are obtained on pure water at pH 2, due to the reduction of electrostatic repulsion by headgroup protonation and the possibility for the formation of a hydrogen bonding network. The divalent cations Mg2+, Ca2+ and Sr2+ interact differently with a DMPG monolayer in pure water at pH 7. In the presence of 1mM CaCl2 a condensation of the DMPG film is induced, whereas an expansion of the monolayer is observed in the presence of Mg2+ and Sr2+. Two counteracting effects are operative: (a) ionization of the headgroup due to electrostatic screening leads to film expansion and (b) binding of the divalent cations to the lipid headgroups leads to condensation. The latter effect is more pronounced in the case of Ca2+, whereas the binding of Mg2+ and Sr2+ to DMPG is weaker. Site-specific cation binding has to be assumed in addition to electrostatic effects.     

Efficacy of sulfadoxine-pyrimethamine in Tanzania after two years as first-line drug for uncomplicated malaria: assessment protocol and implication for treatment policy strategies

Background

Early diagnosis and effective treatment with an appropriate drug form the main components of the World Health Organization's strategy to reduce malaria related mortality. The few available drugs might be safeguarded if combined with artesunate. The addition of artesunate to a standard antimalarial treatment substantially reduces treatment failure, recrudescence and gametocyte carriage.

Methods

During late 2004, the efficacy of artesunate (4 mg/kg. day, on days 0–2) plus sulfadoxine-pyrimethamine (25 mg/kg, on day 0) for the treatment of uncomplicated Plasmodium falciparum malaria was investigated in four sentinel areas in Sudan, with different malaria transmission (Damazin, Kassala, Kosti, and Malakal).

Results

Two hundreds and sixty-nine patients completed the 28-day follow-up. On day one, 60 (22.3%) patients were febrile and 15 (5.5%) patients were parasitaemic. On day three, all the patients were afebrile and aparasitaemic. While two patients (0.7%, Kassala) showed late Clinical and Parasitological Failures, the rest (99.3%) of the patients demonstrated Adequate Clinical and Parasitological Response. A gametocytaemia were detected during the follow-up in one patient (0.37%, Kassala). Adverse drug effects were detected in 32 (11.9%) patients

Conclusion

The study showed that AS plus SP is an effective, safe drug in the treatment of uncomplicated P. falciparum malaria in Sudan.     

From heart to mind. The urotensin II system and its evolving neurophysiological role

The discovery of novel biologically active peptides has led to an explosion in our understanding of the molecular mechanisms that underlie the regulation of sleep and wakefulness. Urotensin II (UII), a peptide originally isolated from fish and known for its strong cardiovascular effects in mammals, is another surprising candidate in the regulatory network of sleep. The UII receptor was found to be expressed by cholinergic neurons of laterodorsal and pedunculopontine tegmental nuclei, an area known to be of utmost importance for the on- and offset of rapid eye movement (REM) sleep. Recently, physiological data have provided further evidence that UII is indeed a modulator of REM sleep. The peptide directly excites cholinergic mesopontine neurons and increases the rate of REM sleep episodes. These new results and its emerging behavioral effects establish UII as a neurotransmitter/neuromodulator in mammals and should spark further interest into the neurobiological role of the peptide.     

A novel beta-peptidyl aminopeptidase (BapA) from strain 3-2W4 cleaves peptide bonds of synthetic beta-tri- and beta-dipeptides

A novel bacterial strain that was capable of growing on the beta-tripeptide H-betahVal-betahAla-betahLeu-OH as the sole carbon and nitrogen source was isolated from an enrichment culture. On the basis of physiological characterization, partial 16S rRNA sequencing, and fatty acid analysis, strain 3-2W4 was identified as a member of the family Sphingomonadaceae. Growth on the beta-tripeptide and the beta-dipeptide H-betahAla-betahLeu-OH was observed, and emerging metabolites were characterized. Small amounts of a persisting metabolite, the N-acetylated beta-dipeptide, were identified in both media. According to dissolved organic carbon measurements, 74 to 80% of the available carbon was dissimilated. The beta-peptide-degrading enzyme was purified from the crude cell extract of cells from strain 3-2W4 grown on complex medium. The enzyme was composed of two subunits, and the N-terminal sequences of both were determined. With this information, it was possible to identify the complete nucleotide sequence and to deduce the primary structure of the gene bapA. The gene encoded a beta-peptidyl aminopeptidase (BapA) of 402 amino acids that was synthesized as preprotein with a signal sequence of 29 amino acids. The enzyme was cleaved into two subunits (residues 30 to 278 and 279 to 402). It belonged to the N-terminal nucleophile (Ntn) hydrolase superfamily.