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Based on epidemiologic and clinical evidence, the National Cholesterol Education Program Adult Treatment Panel has identified low-density lipoprotein cholesterol as the primary target for lipid intervention to promote the reduction of high cholesterol through increased awareness and aggressive management of cardiovascular risk factors. These guidelines provide the basis for management of multiple risk factors and applied intervention using diet, exercise, and drug therapy to lower cholesterol levels. Data from primary- and secondary-prevention trials strongly support the rationale for aggressive therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) to significantly reduce morbidity and mortality from coronary heart disease.

We have identified the molecular basis for familial lipoprotein lipase (LPL) deficiency in two unrelated families with the syndrome of familial hyperchylomicronemia. All 10 exons of the LPL gene were amplified from the two probands' genomic DNA by polymerase chain reaction. In family 1 of French descent, direct sequencing of the amplification products revealed that the patient was heterozygous for two missense mutations, Gly188—-Glu (in exon 5) and Asp250—-Asn (in exon 6). In family 2 of Italian descent, sequencing of multiple amplification products cloned in plasmids indicated that the patient was a compound heterozygote harboring two mutations, Arg243—-His and Asp250—-Asn, both in exon 6. Studies using polymerase chain reaction, restriction enzyme digestion (the Gly188—-Glu mutation disrupts an Ava II site, the Arg243—-His mutation, a Hha I site, and the Asp250—-Asn mutation, a Taq I site), and allele-specific oligonucleotide hybridization confirmed that the patients were indeed compound heterozygous for the respective mutations. LPL constructs carrying the three mutations were expressed individually in Cos cells. All three mutant LPLs were synthesized and secreted efficiently; one (Asp250—-Asn) had minimal (approximately 5%) catalytic activity and the other two were totally inactive. The three mutations occurred in highly conserved regions of the LPL gene. The fact that the newly identified Asp250—-Asn mutation produced an almost totally inactive LPL and the location of this residue with respect to the three-dimensional structure of the highly homologous human pancreatic lipase suggest that Asp250 may be involved in a charge interaction with an alpha-helix in the amino terminal region of LPL. The occurrence of this mutation in two unrelated families of different ancestries (French and Italian) indicates either two independent mutational events affecting unrelated individuals or a common shared ancestral allele. Screening for the Asp250—-Asn mutation should be included in future genetic epidemiology studies on LPL deficiency and familial combined hyperlipidemia.

The chemical defensive system of the ladybird Cryptolaemus montrouzieri consists mainly of three related alkaloids. Two of these have been identified as cis-1-(6-methyl-2-piperidyl)propan-2-one (3) and 1-methyl-9-azabicyclo[3,3,1]nonan-3-one (2); the third is very unstable and readily isomerizes to (3).

The metasternal gland secretion of Phoracantha synonyma contains a diversity of volatile components, one of which, 2-hydroxy-6-methylbenzaldehyde (1), is of widespread occurrence in the genus. Threemajor components and several minor components are macrocyclic lactones, of which the following have been positively identified: decan-9-olide (2), (2)-dec-4-en-9-olide (3) and 11-hydroxytetradec-5-en-13-olide (4). The methyl and ethyl esters of 2-methylbutyric and related acids are also present and are responsible for the characteristic odour of the fresh secretion.

The isolation an structural elucidation of β-D- glucopyranose 1,2,6- tris (pyrrole-2-carboxylate) ( buprestin A) (1) and β-D- glucopyranose 6- (4-hydroxybenzoate) 1,2-bis(pyrrole-2-carboxylate) ( buprestin B) (3), bitter principles of beetles of the family Buprestidae , are reported.

The metasternal gland secretion of Phoracantha semipunctata contains five significant volatile components, of which the most abundant is 2-hydroxy-6-methyl-benzaldehyde (1). The second most abundant component, which has been named phoraoanthol, has been shown by synthesis to be (5-ethylcyclopent-1-enyl)methanol (2). The three other components are aldehydes, derivable from phoracanthol and cis- and trans-dihydrophoracanthols, respectively. Apparently all five components are related biosynthetically.