Neocarzinostatin: controlled release of chromophore and its interaction with DNA

A nonagglutinating derivative of wheat germ agglutinin has been prepared that binds to platelets and precipitates an antibody to the lectin. Platelets treated with this inactive derivative released serotonin when exposed to bivalent F(ab′)₂, but not monovalent Fab, fragments of the lectin antibody. Bridging of platelet-bound Fab by an antibody again induced secretion. The F(ab′)₂ or Fab fragments plus IgG, without the derivative, did not induce secretion. This secretion was not affected by indomethacin showing a direct activation of platelets. Platelets treated with con A followed by F(ab′)₂ to con A did not secrete. In addition, lentil lectin failed to release platelet serotonin. The receptors of the lectin derivative are mobile on the platelet surface and their redistribution may lead to secretion.     

Gibberellins from mangrove plants

Gibberellins were isolated from three mangrove plants: A₁ and A₃ from Sonneratia apetala; A₃, A₅ and A₉ from Rhizophora mucranata and A₃, A₄ and A₇ from Bruguiera gymnorhiza. Biological activity of these gibberellins were examined using three bioassays.     

Studies on metabolism of vitamin A. Absorption of retinal (vitamin A aldehyde) in rats

1. Young rats with low reserves of vitamin A were dosed with retinal in groundnut oil, and the stomach, the contents, mucosa and muscles of small intestine, the blood and the liver were analysed at periods up to 24hr. after dosing. 2. Up to 6hr. after the dose, retinal was present in high concentrations in the contents, mucosa and muscles of the intestine. Small but significant amounts were present in blood and liver at all times. 3. The intestinal mucosa and muscles always contained small amounts of retinol and its esters. 4. A study of the distribution of the three forms of the vitamin within the mucosal cell showed that most of the mucosal retinal enters the cell unchanged. 5. When protein-depleted rats were similarly given retinal, the rate of reduction of the aldehyde, and the consequent deposition in the liver of retinol and its esters, progressively decreased with reduced protein intake.     

Effect of nifedipine treatment on oxidative metabolism of peritoneal macrophages and neutrophils of Plasmodium berghei-infected mice.

The oxidative metabolism of peritoneal macrophages (PM) and neutrophils from nifedipine (calcium channel blocker)-treated, Plasmodium berghei (NK 65)-infected and normal infected Swiss Albino mice was studied. A significant fall in oxidative metabolism as evidenced by decreased chemiluminescence (CL) response (P less than 0.001) was recorded both in PM and neutrophils from nifedipine-treated mice compared to the control animals. When the oxidative metabolism of these phagocytes was studied after infection of the host, higher CL response was recorded from both PM and neutrophils isolated during the early course of infection (0-1 and 5-10% parasitaemia) when compared to uninfected mice (P less than 0.001). A similar pattern was observed in the case of nifedipine-treated and infected mice even though the CL response was much lower. The increasing parasite load not only resulted in subnormal CL response but also prolonged the time required for the phagocytes to exhibit peak oxidative activity both in normal infected and CCB-treated infected mice, but the time taken to show peak CL response was shortened following drug administration compared to controls. These observations revealed the profound in vivo effect of CCB on the functioning of phagocytic leucocytes and thereby questions the use of CCB in combination with chloroquine for reversal of drug resistance.     

Shigella dysenteriae type 1 toxin induced lipid peroxidation in enterocytes isolated from rabbit ileum

To evaluate the role of reactive oxygen species (ROS) in Shigella dysenteriae 1 toxin (STx) mediated intestinal infection, the ligated rabbit small intestinal loops were injected with STx. The enterocytes isolated from STx treated rabbit ileal loops had a significantly higher level of lipid peroxidation as compared to enterocytes isolated from control rabbit ileum. To study the role of second messengers in STx mediated intestinal damage, the in vivo and in vitro effects of modulators of lipid peroxidation of enterocytes were used. The presence of Ca²⁺-ionophore A23187 enhanced the extent of lipid peroxidation in enterocytes isolated from the control and STx treated rabbit ileum. However, l-verapamil only marginally decreased the lipid peroxidation level of enterocytes isolated from STx treated rabbit ileum. The in vitro effect of modulators was in agreement with in vivo studies. Dantrolene significantly decreased the extent of lipid peroxidation of enterocytes isolated from STx treated rabbit ileum. PMA significantly increased the lipid peroxidation level of enterocytes isolated from control ileum. However, PMA could not further enhance the lipid peroxidation level of enterocytes isolated from STx treated rabbit ileum. The presence of H-7 significantly decreased the extent of lipid peroxidation of enterocytes isolated from STx treated rabbit ileum. In vitro effect of PMA and H-7 was in agreement with that of in vivo findings. The role of arachidonic acid metabolites, prostaglandins (PGs), in mediating STx induced lipid peroxidation was also studied. The presence of indomethacin (a PG synthesis inhibitor) significantly decreased the lipid peroxidation induced by STx. These findings suggest that lipid peroxidation induced by STx is mediated through cytosolic calcium. The increase in (Ca²⁺)_i leads to activation of PKC.A significant decrease in the enterocyte levels of antioxidant enzymes superoxide dismutase, catalase and reduced glutathione in STx treated rabbit ileum as compared to control was seen. A significant decrease in vitamin E levels was also observed. This suggests that there is decreased endogenous intestinal protection against ROS in STx mediated intestinal infection which could contribute to enterocyte membrane damage that ultimately leads to changes in membrane permeability and thus to fluid secretion.