Inflammatory response and resistance in lead-treated mice.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to Y M Sin.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Carrageenan of different concentrations was injected into the 6-day-old air pouch in mice. It was found that 12 mg carrageenan caused a significant increase of plasma and exudate corticosterone levels at 24 h, while 1 and 3 mg carrageenan could only induce a significant increase of exudate corticosterone at 4 h. Elevation of corticosterone in both plasma and inflammatory exudate appeared to be correlated, suggesting that the exudate corticosterone was derived from the blood circulation. Injection of exogenous histamine and PGE2 into the air pouch induced a significant increase in exudate levels of corticosterone. However, plasma corticosterone increased significantly only after histamine administration, although a slight increase was observed in those injected with PGE2. These findings thus suggest that endogenous histamine and PGE2 which are released during carrageenan-induced acute inflammation, as shown in our previous work, might be responsible for the increase of corticosterone in both plasma and inflammatory exudate.
Acute inflammation was induced by injecting carrageenan into a 6 day old air pouch in mice. Sodium aurothiomalate was then given twice to each of three groups of mice via different routes. It was found that the mice injected intravenously with sodium aurothiomalate showed the most striking reduction in the number of exudate leucocytes in the inflammatory cavity, although the amount of gold found in their inflamed pouch lining tissue was the least. The amount of gold in plasma was highest in the mice injected intravenously with sodium aurothiomalate and the least amount of gold was found in the mice injected directly into the air pouch with sodium aurothiomalate. The amount of gold in the inflamed pouch lining tissue reached its peak at 24 hours after injection and a significant decrease of exudate leucocytes was only seen 24 and 72 hours after injection. The amount of gold in the exudate fluid was negligible at all the times studied. No significant difference was noted in the degree of inflammatory suppression when increasing doses of sodium aurothiomalate were injected into the air pouch. These findings show that there is no direct correlation between the gold concentration in the inflamed tissue and suppression of the inflammatory reactions in the cavity. Chemotactic and phagocytic analysis of leucocytes in the exudate showed that there was a significant suppression of the neutrophil activities in all the mice treated with sodium aurothiomalate. It is therefore concluded that the significant reduction in the number of exudate leucocytes at the carrageenan induced inflammatory site after treatment with sodium aurothiomalate is most likely due to the direct action of gold on the functional activities of circulating neutrophils.
Explore the source record for details and available documents.
Changes in corticosterone levels in plasma and inflammatory exudate were studied in the 6-day-old air pouch of mice. The pouch inflammation in the test group was induced by the injection of carrageenan prepared in physiological saline while the control received only the physiological saline. The results show that exudate and plasma of both groups showed a rapid rise in corticosterone as measured after 30 min and this early rise was probably due to the resulting effect of the ether used during the injection of irritant or vehicle. In contrast, corticosterone levels in the inflammatory exudate of the test group increased with time, reaching a peak at 24 hours after the carrageenan injection. The increased corticosterone levels in the inflammatory exudate appeared to be closely correlated with the increased exudate cell accumulation. This suggests that the increased accumulation of exudate corticosterone in the pouch might play an important role at the inflammatory site by modulating intensity of the inflammatory reactivity caused by the irritant.
Administration of mercuric chloride to young adult mice produced a significant increase in the activity of renal UDP-glucuronyltransferase (UDPGT) measured with harmol as the acceptor substrate. This was observed 10 days after a daily oral dose of HgCl2 (6 micrograms Hg2+/g body wt.). The increase in UDPGT activity was correlated with an accumulation of mercury in the renal tissues and was accompanied by an increase in the apparent Vmax of the glucuronidation reaction without a change in the apparent Km values for harmol or UDPGA. Parallel studies with mercuric sulfide however showed negligible retention of mercury in both the liver or kidney nor was there any change in UDPGT activity compared to control values. The difference in solubilities of the two mercuric salts may be responsible for this observation. The possible mode of activation of UDPGT by mercury treatment is discussed.
Immune inflammation was induced by injecting bovine serum albumin (BSA) into 6-day-old air pouches of mice presensitized with 2 weekly injections of an emulsion containing BSA and complete Freund's adjuvant. Control mice were also similarly pretreated with the same emulsion without BSA. The results show that the numbers of exudate leucocytes in the air pouches of both test and control groups increased and peaked at 4 h and then declined after the antigen challenge. However, the values of exudate leucocytes in the test animals at 4- and 24-hour intervals were significantly lower than those of the control. On the other hand, exudate histamine of the test group peaked at 1 h, and this was significantly higher than that of the control. Injection of exogenous histamine or histaminase with the challenging antigen increased the number of exudate leucocytes in both test and control animals. The findings thus suggest that endogenous histamine released in immune inflammation most probably plays the same role as in non-immune inflammation by enhancing the vascular permeability at the inflammatory site in the early phase of the inflammatory reaction.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The changes in histamine and prostaglandins (PGE2 and PGF) in carrageenan-induced acute inflammation were studied in 6 day old air pouches in mice. A significant elevation of exudate histamine was found 1 hour after the carrageenan injection. Highest vascular permeability at the site of inflammation was also found at 1 hour. Both PGE2 and PGF showed steady increases in the pouch exudate and reached significantly higher levels at 24 hours. The present findings thus suggest that histamine is involved in the early phase of carrageenan-induced inflammation by enhancing vascular permeability. The increases in PGE2 and PGF appear to be closely correlated with the increased exudate cell accumulation. This leads us to suggest that they are likely to be involved in the exudate cell activity rather than in enhancing the vascular permeability which was found to decrease at 4 hours after the carrageenan injection.
Connective tissue mast cells were topographically and quantitatively studied in the newly formed lining tissue of six day old air pouches induced in the dorsal surface of mice. The results showed that the number of mast cells in the cavities innermost lining increased after injection of carrageenan into the cavity. Degranulation of mast cells was also observed. Variations in mast cell numbers in the lining seemed to correlate with the histamine content. These findings suggest that mast cells not only participate in the initiation of the early phase of acute inflammation but also appear to play an important part in regulating and prolonging more chronic inflammatory reactions.
Explore the source record for details and available documents.
An in vivo study of cartilage breakdown in mice was carried out by implanting living and dead, intact or finely minced autologous cartilage back into newly elicited inflammatory tissue of the original donor. At various time intervals, the implants were removed and their loss of proteoglycan and collagen analysed both histologically and biochemically. The results show that only a modest loss of proteoglycan and collagen occurs in the living intact cartilage. Severe loss of proteoglycan was detected in the minced living and dead intact cartilage. The present findings clearly demonstrate that mechanical damage during the mincing of cartilage predisposes this tissue to attack by various types of mediators known to degrade cartilage.
Implantation of minced autologous cartilage into inflamed air pouches in mice allows the study of therapeutic agents on both the inflammatory process and cartilage degradation. Non-steroidal anti-inflammatory agents were found to reduce cell accumulation in response to carrageenan, but were unable to prevent proteoglycan loss from cartilage. In contrast, D-penicillamine had no effect on the inflammatory process but significantly reduced proteoglycan loss. Our findings suggest that the autologous cartilage transplantation model in the mouse may be useful for studying novel anti-arthritic agents.
The effect of non-steroidal anti-inflammation produced in the 6-day old air pouch by carrageenan or calcium pyrophosphate crystals has been examined. The system is a very reproducible way of studying the cellular and vascular components of inflammation. Non-steroidal drugs have different profiles of activity when tested on the inflammation produced with the two irritants. In general, however, the tested compounds showed similar activity on individual models.
The effect of corticosteroid on autologous minced cartilage transplanted into facsimile synovial cavities has been studied. The soluble form of hydrocortisone, as the sodium succinate, reduced proteoglycan loss from cartilage in a dose-dependent manner. In contrast, insoluble hydrocortisone acetate, if given directly into the cartilage-containing cavity, enhanced proteoglycan loss. Injection of the same dose of drug into the inflamed lining tissue reversed this effect. These findings suggest that intra-articular steroid injection may enhance cartilage damage if insoluble preparations are used, but that this may be overcome by injecting into the inflamed lining tissue rather than into the cavity itself.