Fasciola hepatica: effect of 4-amino-6-trichloroethenyl-1,3-benzenedisulfonamide on glycolysis in vitro

In vitro, 4-amino-6-trichloroethenyl-1,3-benzenedisulfonamide, a potent fasciolicide, causes a potent concentration-dependent inhibition of glucose uptake by mature Fasciola hepatica. In F. hepatica treated with the disulfonamide and then fed [U-¹⁴C]glucose, there was a 60% inhibition of glucose utilization and a corresponding inhibition of acetate and propionate formation. Treated fluke parasites possessed much lower levels of adenosine triphosphate, phosphoenolpyruvate, glucose 6-phosphate, and fructose 6-phosphate than untreated parasites and contained higher levels of glycerol and the free sugars fructose and mannose. Direct measurement of the effect of the disulfonamide on the glycolytic enzymes of F. hepatica demonstrated that 3-phosphoglycerate kinase (EC 2.7.2.3) and phosphoglyceromutase (EC 2.7.5.3) were inhibited. It is therefore suggested that the fasciolicidal activity of 4-amino-6-trichloroethenyl-1, 3-benzenedisulfonamide is due to inhibition of the enzymes 3-phosphoglycerate kinase and phosphoglyceromutase which effectively blocks the Embden-Myerhof glycolytic pathway.     

A comparison of the effects of social rearing and social training on approach responding of Gallus chicks

It has been shown in an earlier paper that chicks that were housed and trained in pairs demonstrated a greater resistance to extinction of the neonatal approach response than did chicks that were housed and trained in isolation. The purpose of the present study was to attempt to replicate these results and to determine whether housing or training is the more important factor in generating the previous finding. Eighty-three, white Leghorn chicks were tested in an experiment employing a 2 × 2 factorial design comparing social vs isolate housing and social vs isolate imprinting training on resistance to extinction of a socially-reinforced running response. The data were consistent with the earlier findings and also revealed that the housing condition is more important in producing subsequent social searching than is the training condition.     

In vitro antioxidant properties of the iron chelator pyridoxal isonicotinoyl hydrazone and some of its analogs

Since there are several problems with desferrioxamine (DFO) therapy, pyridoxal isonicotinoyl hydrazone (PIH) has been studied for more than 10 years as a promising new candidate for iron chelation therapy in iron-overload diseases. Iron chelation could also be helpful for experimental treatment of several other pathologies including rheumatoid arthritis and heart ischemia/reperfusion, due to the generation of oxyradicals and lipid peroxidation mediated by delocalized iron. We demonstrate here that sub-millimolar levels of PIH can inhibit the Fe(III)-EDTA/ascorbate-mediated formation of hydroxyl-like radicals as tested by the release of ethylene from 2-keto-4-methylthiobutyric acid (KMB assay) and the formation of malonaldehyde from 2-deoxyribose damage. PIH could also decrease the rates of Fe(III)-EDTA-mediated oxidation of ascorbate and block the peroxidation of liposomes of rat brain phospholipids induced by ferrous iron-EDTA. In all cases the in vitro antioxidant effectiveness of PIH was comparable to its analogs—including salicylaldehyde isonicotinoyl hydrazone—and to DFO. We conclude that PIH and its analogs are effective new candidates against iron-mediated oxidative stress for use in experimental medicine.     

Midtrimester pregnancy interruption and the placental progesterone levels

Placental progesterone contents were studied in 10 patients therapeutically aborted at midtrimester by intraamniotic infusions of hypertonic saline, and from 14 patients (12–20 weeks) aborted by intraamniotic instillation of prostaglandin F_2∝. The mean S.E. of the progesterone was 1.99± 0.07 ug/g. placental tissue in the first group, while with prostaglandin abortion the placental progesterone was 1.45± 0.09 ug/g. tissue, which is significantly lower than the results in the first group (P=0.001). The possible mechanism of action of prostaglandin as an effective abortifacient is discussed.     

Incidence of symptoms and AIDS in 146 Swedish haemophiliacs and blood transfusion recipients infected with human immunodeficiency virus.

The times from infection with the human immuno-deficiency virus (HIV) to the onset of the first clinical symptom and the development of AIDS were studied prospectively in 98 haemophiliacs and 48 blood transfusion recipients infected with the virus. Patients were followed up for a median of 61 months after infection, the dates of infection being either known exactly or estimated from the interval between the last negative and first positive HIV antibody test result. The rate of progression to AIDS was significantly higher for the transfusion recipients than for the haemophiliacs. The difference in time to the occurrence of the first clinical symptom was less pronounced between the two groups, though pointing in the same direction. The results suggest that on average roughly half of all patients positive for HIV will develop some clinical sign or symptom within five to six years after infection.