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I L Bonta

Publications and source records attributed to I L Bonta.

At least 19 recordsLinked to original sources
PubMed1979

Distribution and further studies on the activity of prostaglandin E in chronic granulomatous inflammation.

Pre-formed granulomata, induced by cannulated, carrageenin-soaked, subdermal sponge implants, were used to further analyse the effects of exogenous PGE and the involvement of endogenous PGE in this model of chronic inflammatory tissue changes in rats. Experiments with 14C-PGE2 indicated that administration of PGE into the sponge creates a kinetic situation likely to imitate, but superimposed upon, the continuous discharge of endogenous PGE in the granuloma. The granuloma-reducing, anti-flammatory effect of PGE can be mimicked by dibutyryl cyclic-AMP, phosphodiesterase inhibitors and indomethacin. Most probably these compounds, in common with PGE, exert their anti-granuloma action through elevation of intracellular cyclic-AMP (in macrophages and/or fibroblasts). The anti-granuloma action is not necessarily associated with a reduction in the endogenous PGE-level and vice versa. The involvement of endogenous PGE in the tissue events of granulomatous inflammation is conjectural as yet.

Animals↗
PubMed1979

Effects of 2-aminomethyl-4-t-butyl-6-iodophenol (MK-447) on granulomatous inflammation: lack of correlation with changes in levels of prostaglandin-like material.

MK-447, administered locally to carrageenan-soaked sponges implanted in the backs of rats, either on the day of implantation (day 1) or on days 4-7, exhibited a weak, dose-related inhibition of subsequent granuloma formation. With the later treatment period, prostaglandin (PG)-like material in day 8 exudates was increased at all doses, but with MK-447 treatment on day 1, levels of PG-like material after 24 h were unaffected. Thus, inhibition of granuloma formation was unrelated to local levels of PG-like material. Following treatment with low doses of MK-447 on implantation, mononuclear cell counts in 24 h exudates were reduced. Similar results were obtained with PGE1. Higher doses of MK-447 did not alter monuclear cell counts, but both high and low doses of MK-447 markedly increased polymorphonuclear cell counts in 24-h exudates. The results do not permit the conclusion that the anti-granuloma action of MK-447 is necessarily related to alteration of stable PG level at the inflamed site. Therefore, MK-447 cannot be used unequivocably as a tool to investigate the role of endogenous stable PGs during granulomatous inflammation.

Animals↗
PubMed1979

The use of essential fatty acid deficient rats to study pathophysiological roles of prostaglandins. Comparison of prostaglandin production with some parameters of deficiency.

In a retrospective study on essential fatty acid deficient (EFAD) rats used to study pathophysiological roles of prostaglandins (PGs), slight increases in the linoleic acid content of the diet were found to gradually restore the depressed growth rate and to increase the reduced endogenous PG production. These apparently poorly deficient animals had a serum triene tetraene (omega9:omega6) ratio much higher than the value of 0.4 used as a criterion for EFA deficiency by nutritionists. Changes in body weight, serum omega9:omega6 and platelet PG production were not correlated with each other. Feeding rats on a diet containing less than 0.1 mg/g/linoleic acid led to decreasing platelet PG production as the degree of EFA deficiency increased. At this high level of deficiency, a serum omega9:omega6 ratio of 6 or over was achieved. This high ratio may be taken as an indicator of the degree of EFA deficiency required for studies on PG deprivation, but PG production by the tissue investigated or by platelets should preferentially be measured.

Animals↗
PubMed1979

Dissociation between prostaglandin and malondialdehyde formation in exudate and increased levels of malondialdehyde in plasma and liver during granulomatous inflammation in the rat.

During kaolin-induced granuloma pouch inflammation in the rat the concentration of malondialdehyde (MDA) in the exudate, measured by the 2-thiobarbiturate method, steadily increased and this increase was correlated with the increase in granuloma weight. There was a complete lack of correlation between the concentrations of MDA and prostaglandin (PG)-like material in the inflammatory exudate. Whereas the concentration of PGs reached a maximum 1 day after the induction of inflammation and returned to control levels on day 4, the MDA concentration continuously increased from the initiation of inflammation up to day 16. During granuloma development the concentration of MDA in the plasma reached a maximum on day 2 in parallel with the concentration in the liver, then both plasma and liver MDA decreased to levels observed in control rats. Between day 2 and 8 of the inflammatory process homogenates of livers from inflamed rats showed an increased formation of MDA on incubation, the amount formed being maximal on day 4. The results of the present study are discussed in view of a possible involvement of lipid peroxidation in inflammation.

Animals↗
PubMed1979

Time-dependent stimulatory and inhibitory effects of prostaglandin E1 on exudative and tissue components of granulomatous inflammation in rats.

1 The effects of prostaglandin (PGE(1)), following local administration during different phases of developing sponge-induced granulomata, were studied in normal and essential fatty acid deficient (EFAD) rats.2 In normal rats, a single dose of 1 mug PGE(1) on implantation (day 1) increased exudate production without altering total leucocyte counts after 6 h and stimulated granulomatous tissue formation after 8 days.3 Repeated daily administration of the same dose of PGE(1) on days 1 to 3 had no effect, while administration on days 4 to 7 (i.e. when tissue growth is already in progress) inhibited granuloma formation.4 In EFAD rats, which are known to produce only very small amounts of endogenous prostaglandins, acute (6 h) exudate formation was unaffected by 0.05 mug PGE(1). However, early stimulatory and later inhibitory effects of 0.05 mug PGE(1) per day were obtained on the granulomatous tissue, similar to those obtained with the 20 fold higher dose in normal rats.5 The early stimulatory action of PGE(1) on granulomatous tissue formation was enhanced, in normal rats, by concomitant administration of 10 mug theophylline. This latter compound did not influence the later inhibitory effect of PGE(1).6 These results indicate that PGE(1) exerts either pro- or anti-inflammatory actions on the proliferative (tissue) component of the inflammatory process, depending on the time of administration. While the stimulatory effect following early administration may have been secondary to an initial cyclic adenosine 3',5'-monophosphate-mediated, vascular response, such a mechanism is unlikely to have been responsible for the later anti-inflammatory action of PGE(1).7 The implications of these results are discussed in relation to the postulated negative-feedback role of endogenous PGE in chronic inflammation.

Animals↗
PubMed1979

Prostaglandins and granuloma formation in vivo.

The formation of granuloma tissue is one of the major characteristics of chronic inflammation. Infiltration of phagocytic cells (a major source of prostaglandins) and in many cases (including rheumatoid arthritis) lymphocytes, is one of the earliest events in granuloma formation. Prostaglandins (PGs) may modulate the infiltration of some or all of these cells, though much in-vivo data is lacking. Additionally, PGs may modulate the release of the products of these inflammatory cells, which contribute to granuloma formation. Once granulomatous tissue becomes established, PGs may also control the growth of the granuloma through actions on proliferating cells and connective tissue constituents. In-vivo data suggest that the anti-granuloma actions may be mediated by cyclic AMP. While prevention of endogenous PG production by anti-inflammatory drugs has little beneficial effect on preexisting granuloma, facilitation or mimickry of the anti-granuloma actions of PGs may be a possible line for future therapy of diseases such as rheumatoid arthritis.

Animals↗
PubMed1979

Modulation of granulomatous inflammation by prostaglandin E. Involvement of mononuclear cells.

The effects of exogenous PGE, administered locally to carrageenan sponge-induced granulomata in rats, have been studied in relation to changes in PGE-like material (PGL) and cell counts in exudates. Levels of PGL achieved a peak within 24h, declining thereafter. Administration of PGE during the acute phase led to irregular slight enhancement of subsequent granuloma formation. In contrast, administration of exogenous PGE to pre-formed granuloma, inhibited its formation. The early administration of PGE1, on day 1, inhibited mononuclear cell counts in 24h exudates. This inhibition was still present in 8 day exudates, together with reduced PGL levels. A significant correlation was also observed between phagocytosing macrophages and PGL levels in 8 day exudates after exogenous PGE1 treatment of pre-formed granuloma, suggesting that the exogenous PGE was inhibiting macrophage function, including PGL production. Further studies are necessary to establish whether the observed pharmacological effects indicate that PGE, released during granulomatous inflammation, modulates the process through actions on infiltrating leucocytes.

Animals↗
PubMed1979

Mimickry of anti-granuloma effect of prostaglandin E by dibutyryl cyclic-AMP and some phosphodiesterase inhibitors.

Local administration of PGE1 to pre-formed inflammatory granulomata of rats results in a decrease of granulomatous tissue and reduction of prostaglandin concentrations in granulomatous exudates. Under the same experimental conditions, a similar correlation between these two effects is observed with dibutyryl cyclic-AMP. An anti-granuloma effect is also achieved with the phosphodiesterase inhibitors, IBMX and RA-233, but not with theophylline, a rather feeble inhibitor of this enzyme. The present findings provide further support for the concept that elevation of cyclic-AMP in cell population(s) within granuloma is a promising line for pharmacological suppression of inflammatory tissue proliferation.

1-Methyl-3-isobutylxanthine↗
PubMed1978

Accumulation of blood platelets in carrageenin rat paw oedema. Possible role in the inflammatory process.

The accumulation of blood platelets in the carrageenin-induced paw oedema in rats was studied, using 51Cr-labeled platelets. A maximum in the accumulation was seen after 4 hours, followed by a decline after 5--6 hours. During the first 6 hours of the oedema formation, change in blood volume were small. A comparison was made with the accumulation of both 125J-albumin as a measure of extravasation and 125J-fibrinogen as an indication of blood clotting. When platelet aggregation was measured during the first 6 hours of the oedema formation, the lag time between the addition of collagen and the beginning of the aggregation was increased. No change in platelet serotonin was seen. These data support the idea that platelets participate in the inflammatory process.

Animals↗
PubMed1978

Combination of theophylline and prostaglandin E1 as inhibitors of the adjuvant-induced arthritis syndrome of rats.

The effects of daily subcutaneous administration of prostaglandin E1 (PGE1), theophylline, and of both drugs together were studied on the Freund's adjuvant-induced inflammatory and arthritic syndrome in rats. In the doses used, neither drug affected the acute inflammatory response in the adjuvant-treated paw, but together they caused marked inhibition. Chronic inflammation in the contralateral (nontreated) hind paws was slightly inhibited by each drug and combined treatment resulted in marked inhibition. The drugs also counteracted splenomegaly in adjuvant-diseased rats and their effects on spleen weight paralleled the inhibition of chronic inflammation. Arthritic lesions, as judged by x-rays of tibiotarsal joint destruction in the nontreated paws, were partially prevented by PGE1 alone, but not by theophylline. The combined treatment entirely prevented these joint lesions. PGE1 did not cause an increase in adrenal weight, but enhanced the effect of theophylline on adrenal weight. Only PGE1 improved gait in arthritic rats, simultaneous theophylline treatement having little additional effect. Other workers have found the PGE1 increases intracellular cAMP and that this effect is enhanced by the phosphodiesterase inhibitor, theophylline. We propose that the anti-inflammatory and anti-arthritic effects of combined drug treatment involve cAMP changes in phagocytic cells at the site of tissue injury and in systemic lymphocytes.

Animals↗