Malaria is a major disease of humans caused by protozoan parasites from the genus Plasmodium. It has a complex life cycle; however, asexual parasite infection within the blood stream is responsible for all disease pathology. This stage is initiated when merozoites, the free invasive blood-stage form, invade circulating erythrocytes. Although invasion is rapid, it is the only time of the life cycle when the parasite is directly exposed to the host immune system. Significant effort has, therefore, focused on identifying the proteins involved and understanding the underlying mechanisms behind merozoite invasion into the protected niche inside the human erythrocyte.

No abstract

Breast cancer can be treated with chemotherapy during the second and third trimesters of pregnancy with minimal complications of labor and delivery.

In the semisynthetic compound phorbol 12-retinoate 13-acetate (PRA), the antipromoting principle of vitamin A acid is combined with the structure of a phorbol ester tumor promoter. In skin of NMRI mice, a single topical application of PRA induces skin inflammation, epidermal proliferation, and sustained hyperplasia to a similar extent and apparently along the same pathway as an equimolar dose of the strong tumor promoter phorbol 12-myristate 13-acetate (PMA). The mitogenic effects of both PRA and PMA are mediated by prostaglandin E synthesis. However, in mouse skin initiated with 7,12-dimethylbenz[a]anthracene, PRA does not promote tumor development, even at a high dose. Under continuous PRA treatment, however, one to four applications of PMA (insufficient by itself to promote tumor growth) gave a strong tumor response. Thus, it can be demonstrated that the effects necessary for tumor promotion can be brought about by a single application of PMA and that the subsequent chronic hyperproliferation of epidermis is probably necessary only to make the tumors visible. By using the nonpromoting irritant mitogen PRA, the concept of two-stage tumor promotion can thus be strongly supported. Furthermore, in the NMRI mouse, PRA is a much more potent second-stage promoter than mezerein, recently reported to be an incomplete promoter in the Sencar mouse.In mouse skin, tumor promotion can be brought about by a single application of a subthreshold dose of a carcinogen followed by repetitive applications of a noncarcinogenic promoter. One ofthe most potent skin tumor promoters is phorbol 12-myristate 13-acetate (PMA, I). Although the promoting effect of PMA seems to be inseparably linked to inflammatory effects and epidermal hyperproliferation (1, 2), the mechanism of action of phorbol ester tumor promoters is still a mystery because irritant skin mitogens have been described that induce epidermal hyperproliferation as effectively as PMA without being potent tumor promoters. These include the weakly promoting phorbol ester-type compounds phorbol 12-tetradecatetra-2,4,6,8-enoate 13-acetatet (II; refs. 3 and 4) and mezerein (5, 6) and the nonpromoting ionophore A23187 (7). Thus, the induction of cellular proliferation is possibly a necessary but certainly not a sufficient condition for tumor promotion. A similar conclusion has been drawn from studies oftumor promotion in cell cultures (8,9

Objective: To report our experience with intentional puncture of the intervening membrane (‘septostomy’) for the treatment of the twin oligohydramnios-polyhydramnios sequence (TOPS). Methods: 12 patients were diagnosed with TOPS based on ultrasonographic findings. A 20- to 22-gauge spinal needle was used to puncture the membrane between the twins without any attempt at amnioreduction in 9 patients, while the procedure was combined with amnioreductions in 3 patients. Results: Gestational age was 23.1 ± 3.3 weeks at the time of septostomy and 31.1 ± 4.4 weeks at delivery. Rapid accumulation of fluid around the ‘stuck’ fetus occurred in all cases following a single procedure. Three of the 24 fetuses died in utero and 1 died on the fifth day of life, for a combined survival of 83.3%. In the survivors, the septostomy to delivery interval ranged between 0.6 and 13 weeks (mean ± SD 8.3 ± 4.8). Conclusion: Amniotic septostomy is a promising new method for the management of TOPS and is associated with survival rates that are better than, or comparable to, more invasive modalities. A multicenter trial comparing septostomy to other modalities is warranted.

No abstract

No abstract

Lipoxygenase was extracted from mouse epidermal cells and partially purified by ammonium sulfate precipitation. Using a biological oxygen monitor for activity measurements and linoleic acid as substrate, the effect of a series of flavonoids on lipoxygenase activity was determined. Flavone itself did not inhibit lipoxygenase, but hydroxylated derivatives retaining the double bond in the 2,3 position and having a hydroxyl group in the 3 position (such as quercetin and 3-hydroxy-flavone) were potent lipoxygenase inhibitors compared to flavonoids without those particular functional groups.