Dynamic light scattering studies of irradiated kappa carrageenan

Investigation of the dynamic behavior of irradiated kappa carrageenan (in KCl) as a function of irradiation dose and temperature was done by dynamic light scattering (DLS). The intensity correlation function (ICF) shifted towards shorter relaxation times with increasing radiation dose as a result of radiolysis. The characteristic decay time distribution function, G(gamma), indicates the presence of fast and slow mode peaks respectively at around 0.1-10 ms and 100-1000 ms. A peak broadening of the fast mode peak in G(gamma) appeared with decreasing temperature, indicating that coil-to-helical conformational transition took place. The conformation transition temperature (CTT) decreased with increasing radiation dose. No transition was observed for kappa-carrageenan irradiated at 200 kGy. A new faster relaxation mode appeared at around 0.1-1 ms at temperatures below the CTT. This peak is found in kappa-carrageenan irradiated at doses exclusively between 75 and 175 kGy. The peak height of this mode is largest at 100 kGy which corresponds to the optimum biologic activity of kappa-carrageenan reported previously.     

Inhibition of carrageenan edema by carrageenan itself]

The influence of two kinin forming agents: iota carrageenan and ellagic acid, on the paw oedema induced by 48/80, an amino-liberator, or by carrageenan iota, has been studied, in the Rat. Ellagic acid and carrageenan, by intraperitoneal injection, reduce the paw oedema induced respectively by 48/80 and carrageenan itself. This inhibition depends on a non-specific "counter-irritation" and not on kininogen stores depletion. Ellagic acid, by intravenous injection, diminishes the oedema induced by carrageenan; swelling due to 48/80, is not affected. So kininogen activation plays some role in the inflammatory processes induced by iota carrageenan. Carrageenan by intravenous injection, suppresses his own inflammatory action but does not influence at all the similar action of 48/80. The anti-inflammatory effect of carrageenan does not exclusively depend on kininogen stores depletion.     

Role of platelets in arterial hypotension induced by arachidonic acid and in carrageenan induced edema in the rat]

When rat platelets are incubated in vitro in the presence of aspirin, the formation of malonaldehyde from arachidonic acid is inhibited. The production of malonaldehyde reflects the synthesis of prostaglandins and associated compounds. The same inhibition is found when the platelets originate from rats pretreated with aspirin. Small doses of aspirin are active in vitro and 10-20 mg/kg in vivo. This dosage of aspirin does not affect the hypotensive activity of arachidonic acid nor the oedematous properties of carrageenan in the rat. These two effects are thus independent from the prostaglandins formed in the platelets.     

IL-1 and its role in rat carrageenan pleurisy

The carrageenan pleurisy model, which is characterized by cellular influx and oedema, has been used to examine the effects of anti-inflammatory compounds such as naproxen. Interleukin-1alpha and beta (IL-1) are known to be pro-inflammatory mediators, and their roles in this model are unknown. Intrapleural injection of 1% viscarin carrageenan or saline was administered to male Lewis rats. Four to 24 h later, cell counts, fluid volumes and IL-1beta levels (measured by ELISA) were determined in the pleural cavity. Serum corticosterone levels were measured only at 4 h. Significant increases in IL-1beta levels precede cell influx suggesting IL-1beta plays a role in the maintenance of cell accumulation in the pleural cavity. None of the drugs tested, including the IL-1 receptor antagonist, maintained pleural cell influx and IL-1beta levels at control levels. When human IL-1alpha or beta or rat IL-1beta were injected individually into the pleural cavity, none of these cytokines were pro-inflammatory, as measured by increased cell influx and fluid extravasation. These results suggest that although IL-1beta levels increase in the pleural cavity in response to carrageenan, IL-1 per se is not the initiator of the pro-inflammatory events of cell influx and oedema in this model.     

Protective effects of n-acetylcysteine on lung injury and red blood cell modification induced by carrageenan in the rat.

Oxidative stress has been suggested as a potential mechanism in the pathogenesis of lung inflammation. The pharmacological profile of n-acetylcysteine (NAC), a free radical scavenger, was evaluated in an experimental model of lung injury (carrageenan-induced pleurisy). Injection of carrageenan into the pleural cavity of rats elicited an acute inflammatory response characterized by fluid accumulation in the pleural cavity that contained many neutrophils (PMNs), an infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate, tumor necrosis factor alpha, and interleukin 1beta. All parameters of inflammation were attenuated by NAC treatment. Furthermore, carrageenan induced an up-regulation of the adhesion molecules ICAM-1 and P-selectin, as well as nitrotyrosine and poly (ADP-ribose) synthetase (PARS), as determined by immunohistochemical analysis of lung tissues. The degree of staining for the ICAM-1, P-selectin, nitrotyrosine, and PARS was reduced by NAC. In vivo NAC treatment significantly reduced peroxynitrite formation as measured by the oxidation of the fluorescent dihydrorhodamine-123, prevented the appearance of DNA damage, an decrease in mitochondrial respiration, and partially restored the cellular level of NAD+ in ex vivo macrophages harvested from the pleural cavity of rats subjected to carrageenan-induced pleurisy. A significant alteration in the morphology of red blood cells was observed 24 h after carrageenan administration. NAC treatment has the ability to significantly diminish the red blood cell alteration. Our results clearly demonstrate that NAC treatment exerts a protective effect and clearly indicate that NAC offers a novel therapeutic approach for the management of lung injury where radicals have been postulated to play a role.     

Hypotensive and sedative effects of insulin in autonomic failure.

The haemodynamic responses to intravenous insulin (0.15 units/kg) were measured in five patients with chronic autonomic failure who were not receiving drug treatment. After the administration of insulin supine blood pressure fell steadily, with a substantial reduction even before the onset of hypoglycaemia. None of the patients showed the usual range of neuroglycopenic symptoms, but they all became drowsy, with increasing sedation as the blood glucose concentration fell. In four other patients with autonomic dysfunction intravenous injection of 25-50 ml of 50% glucose alone caused a striking, although transient, fall in blood pressure. Hypoglycaemia was reversed by a 10 minute intravenous infusion of 100 ml of 25% glucose; this did not lower blood pressure further and rapidly restored previous levels of alertness. Consideration must be given to the hypotensive potential of insulin in patients with autonomic failure during an insulin stress test. The inability of these patients to show the usual manifestations of hypoglycaemia, plus the short lived, though pronounced, reduction in blood pressure after intravenous administration of 50% glucose, may further increase the risks of this procedure.     

Hypotensive response to prostacyclin and 6-keto-PGE1 following hepatectomy in the rat

Prostacyclin (PGI2) is metabolized to 6-keto-prostaglandin E1 (6-keto-PGE1) which is more stable yet equipotent to PGI2 in lowering systemic arterial blood pressure in the dog. In this study, partial hepatectomy was performed to determine the role of the liver in the vasodepressor response to both intravenously administered PGI2 and 6-keto-PGE1. The magnitude and the duration of systemic hypotensive responses were measured in hepatectomized and sham-operated male Wistar rats following less than maximal, equidepressor doses of PGI2 (0.3 microgram/kg), 6-keto-PGE1 (1.0 microgram/kg), and also PGE1 (3.0 micrograms/kg) and PGE2 (3.0 micrograms/kg). Hepatectomy did not significantly alter the magnitude of the systemic hypotensive response to any of the prostaglandins tested. This indicates that the liver and hepatic circulation do not contribute significantly to the hypotensive effect of these prostaglandins by alterations of systemic vascular resistance, venous pooling of blood, or the generation of additional vasoactive metabolites as may be expected following administration of these prostaglandins. However, hepatectomy did significantly increase the duration of the hypotensive response to PGI2 and 6-keto-PGE1 but not PGE1 or PGE2. We conclude that in vivo, the liver has a more significant role in PGI2 and 6-keto-PGE1 inactivation than in the inactivation of PGE1 and PGE2 when administered intravenously. These results also support the relatively greater significance of the lung in the inactivation of PGE1 and PGE2 in vivo.     

Toxic effects of heavy metal salts on intact and irradiated cultured mammalian cells]

The toxicity of solutions of K2Cr2O7 and NiSO4.8H2O for cultivated Chinese hamster fibroblasts and murine lymphoma Sp-2 cells was determined using three criteria of damage: cell death (dyeing with trypan blue), inhibition of cell proliferation and their colony-forming activity. It was shown that both salts have equal toxicity in (10(-3)-10(-2)) M interval for both culture investigated relative to inhibition of cell proliferation. The threshold of toxicity of K2Cr2O7 relative to reproductive cell death (10(-4) M is smaller than to the inhibition of cell proliferation. The nontoxic concentration of K2Cr2O7 enhanced the radiation-induced reproductive death of fibroblast culture at doses 2 and 4 Gy.     

Hypotensive and renal effects of an extract of the edible mushroom Pleurotus sajor-caju

An aqueous extract of Pleurotus sajor-caju was found to have a hypotensive effect in rats. Intravenous infusion of the extract into rats caused a decrease of the mean systemic blood pressure in a dose dependent manner. A typical dose of 25 mg of the extract decreased the mean systemic blood pressure from 110 mm Hg to 70 mm Hg. The systolic and diastolic pressure changed proportionally with minimal alteration in heart rate. The hypotensive effect of the extract was not due to its major electrolyte content because a solution reconstituted with the same electrolyte composition had a transient pressor effect rather than lowering the blood pressure. The same extract was also found to affect renal hemodynamics such that it caused a decrease in the glomerular filtration rate by more than 50% after 120 minutes. The effect did not seem to be mediated through changes in systemic blood pressure.