ACAT inhibitors derived from hetero-Diels-Alder cycloadducts of thioaldehydes

Acyl-CoA:cholesterol acyltransferase (ACAT) is the enzyme largely responsible for intracellular cholesterol esterification. A systemic inhibitor of ACAT is believed to be able to slow or even reverse the atherosclerotic process. Towards that goal, a series of cyclic sulfides, derived from the hetero-Diels-Alder reaction of thioaldehydes with 1,3-dienes, and bearing carboxamide substituents, were prepared and evaluated for in vitro (in several tissues and species) and ex vivo ACAT inhibition. Minor changes in subsequent structure were found to have a significant effect in optimization of the biological activity of this series of compounds.     

Cell cycle. The NIMA kinase joins forces with Cdc2

The NIMA and Cdc2 protein kinases cooperate to regulate mitosis in Aspergillus nidulans. NIMA-related pathways have now begun to emerge in higher eukaryotes.     

A new epitope presenting system displays a HIV-1 V3 loop sequence and induces neutralizing antibodies

The principal neutralizing domain, IGPGRAF sequence, from the V3-loop of HIV-1 was inserted in two positions on the surface of the protein that makes up the capside shell of the insect Flock House Virus. The hybrid proteins were expressed in insect cells via recombinant baculoviruses. Three different hybrids were used as immunogens: two with a single copy of the insert in different positions of the carrier protein and a third with two copies of the insert at the same positions as before. All hybrid proteins induced strong and broad specific immune response in guinea pigs against different V3-loop sequences. However, only one of the hybrid proteins was able to induce a strong neutralizing response against MN and IIIB HIV-1 isolates. Our results demonstrate that a very short peptide sequence of HIV-1 can constitute a valuable immunogen able to induce a neutralizing response if presented to the immune system in the context of the FHV capsomer structure.     

Caudascopic experiences and a new patho-anatomic concept for treatment of sciatica

Osteotomy has been used in treatment of unstable intertrochanteric hip fractures in an attempt to increase the stability of the fracture fragments. We have assessed this stability in a randomised prospective study on 138 patients, all having been fixed by dynamic hip screen, comparing anatomical reduction with medialisation osteotomy. The groups were similar in terms of age, gender and fracture configuration. There was no difference in final results in both groups except that operation time was longer in osteotomy group and the blood loss was more. We found no clear benefit from osteotomy and therefore recommend anatomical reduction and fixation by a sliding hip screw in most cases. Rarely, a fracture configuration which does not allow anatomical reduction may benefit from an osteotomy.     

A long-term follow-up study of patients with ischaemic heart disease versus patients with nonspecific chest pain

Ninety consecutive patients who were admitted to hospital with acute chest pain were followed-up five years later. At the time of the original admission, all of the patients received a detailed physical and psychiatric evaluation. Seventy-one patients were diagnosed as having ischaemic heart disease, and 19 were diagnosed as having nonspecific chest pain. Patients with nonspecific pain were younger, consumed greater amounts of alcohol, smoked more than their organic counterparts, and were more likely to suffer from psychiatric disorder. The five-year assessment was carried out using a self-report questionnaire. Of the original 71 patients with ischaemic heart disease, 14 had died; 43 questionnaires were returned, 80.2% of the original sample. Sixteen (84.9%) of the patients with nonspecific pain were followed up; none had died. Both groups were predominantly male. The patients with nonspecific pain still smoked more than the patients with ischaemic heart disease, and they had significantly more symptoms of anxiety. The overall prevalence of psychiatric morbidity remained high, however, in both groups. Patients who had psychiatric illness at the time of the original assessment were more anxious at follow-up and more likely to complain of chest pain than those who had been well. Patients with nonspecific chest pain continued to seek treatment on a regular basis from their general practitioners either for chest pain or for other symptoms, but few were in frequent contact with hospital services. The possible preventive effects of psychiatric intervention at an earlier stage in both groups of patients needs to be investigated.