The 'causes' of teenage pregnancy: review of South African research - Part 2

This article forms the second of a two-part series in which South African research on teenage pregnancy is reviewed. Part 1 of the series dealt with the consequences of teenage pregnancy; this paper reviews the 'causes' thereof. International literature is incorporated in the discussion by way of comparison. Contributory factors which have been investigated by South African researchers include: reproductive ignorance; the earlier occurrence of menarche; risktaking behaviour; psychological problems; peer influence; co-ercive sexual relations; dysfunctional family patterns; poor health services; socio-economic status; the breakdown of cultural traditions; and the cultural value placed on children. Preston-Whyte and colleagues present a revisionist argument, stating that early pregnancy may represent a rational life choice for certain adolescent women. The article is concluded with comments on methodological problems encountered in the South African research, and a discussion on the implications in terms of policy formulation

Anti-inflammatory apoA-I-mimetic peptides bind oxidized lipids with much higher affinity than human apoA-I*

4F is an anti-inflammatory, apolipoprotein A-I (apoA-I)-mimetic peptide that is active in vivo at nanomolar concentrations in the presence of a large molar excess of apoA-I. Physiologic concentrations (∼35 μM) of human apoA-I did not inhibit the production of LDL-induced monocyte chemotactic activity by human aortic endothelial cell cultures, but adding nanomolar concentrations of 4F in the presence of ∼35 μM apoA-I significantly reduced this inflammatory response. We analyzed lipid binding by surface plasmon resonance. The anti-inflammatory 4F peptide bound oxidized lipids with much higher affinity than did apoA-I. Initially, we examined the binding of PAPC (1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidylcholine) and observed that its oxidized products bound 4F with an affinity that was ∼4–6 orders of magnitude higher than that of apoA-I. This high binding affinity was confirmed in studies with defined lipids and phospholipids. 3F-2 and 3F14 are also amphipathic α-helical octadecapeptides, but 3F-2 inhibits atherosclerosis in mice and 3F14 does not. Like 4F, 3F-2 also bound oxidized phospholipids with very high affinity, whereas 3F14 resembled apoA-I. The extraordinary ability of 4F to bind pro-inflammatory oxidized lipids probably accounts for its remarkable anti-inflammatory properties

A novel method for oral delivery of apolipoprotein mimetic peptides synthesized from all L-amino acids

Administered subcutaneously, D-4F or L-4F are equally efficacious, but only D-4F is orally efficacious because of digestion of L-4F by gut proteases. Orally administering niclosamide (a chlorinated salicylanilide used as a molluscicide, antihelminthic, and lampricide) in temporal proximity to oral L-4F (but not niclosamide alone) in apoE null mice resulted in significant improvement (P < 0.001) in the HDL-inflammatory index (HII), which measures the ability of HDL to inhibit LDL-induced monocyte chemotactic activity in endothelial cell cultures. Oral administration of L-[113-122]apoJ with niclosamide also resulted in significant improvement (P < 0.001) in HII. Oral administration of niclosamide and L-4F together with pravastatin to female apoE null mice at 9.5 months of age for six months significantly reduced aortic sinus lesion area (P = 0.02), en face lesion area (P = 0.033), and macrophage lesion area (P = 0.02) compared with pretreatment, indicating lesion regression. In contrast, lesions were significantly larger in mice receiving only niclosamide and pravastatin or L-4F and pravastatin (P < 0.001). In vitro niclosamide and L-4F tightly associated rendering the peptide resistant to trypsin digestion. Niclosamide itself did not inhibit trypsin activity. The combination of niclosamide with apolipoprotein mimetic peptides appears to be a promising method for oral delivery of these peptides