Tag Archives: inflammation

Systemic Inflammatory Effects During the Acute Phase of Experimental Pleurodesis in Rabbits: Conclusion

Systemic Inflammatory Effects During the Acute Phase of Experimental Pleurodesis in Rabbits: ConclusionAlthough there have been reports of adverse systemic effects in humans when TL has been administered intrapleurally, there have been limited reports on the systemic effects after the intrapleural administration of this low dose of SN. One study (an abstract) injected the same concentration of SN in an attempt to induce pleurodesis in patients with malignant pleural effusions. In that clinical study, 47 patients were randomized to receive 5 g TL slurry or 20 mL 0.5% SN. In that study, TL was effective in 21 of 24 patients (87.5%), and SN was effective in 22 of 23 patients (95.6%). The only significant side effect was pain requiring therapy with analgesics. No patient receiving either drug developed ARDS.
We also observed that both agents produced an acute and intense pleural inflammation, which was more pronounced with SN. For the TL group, pleural fluid WBC count, neutrophil percentage, and LDH level increased in the first 6 h and tended to decrease with time, which is similar to what was observed in the blood. For the SN group, the cellular influx to the pleural cavity was acute and was sustained with a progressive increase in LDH level.

Systemic Inflammatory Effects During the Acute Phase of Experimental Pleurodesis in Rabbits: LDH

It has been hypothesized that this systemic dissemination of TL is more likely if TL with a smaller mean particle size is used.- TL particles have been shown to vary markedly in median particle size.” It is hypothesized that small TL particles can enter the lymphatic system in the parietal pleura and subsequently can gain access to the systemic circulation. It should be noted that in the present study, TL with a relatively high mean particle size was used. It would be interesting to compare the systemic responses to animals that receive relatively large and relatively small TL particles. A second possible mechanism for the systemic inflammatory response induced by the administration of TL intrapleurally is the transpleural transfer of TL, which then could induce inflammation in the lung. A third possible mechanism is the systemic absorption of TL contaminants such as endotoxin.

Systemic Inflammatory Effects During the Acute Phase of Experimental Pleurodesis in Rabbits: Discussion

Systemic Inflammatory Effects During the Acute Phase of Experimental Pleurodesis in Rabbits: DiscussionSN also induced a systemic response, with increases in serum LDH, IL-8, and VEGF levels. The serum LDH level increased 6 h after injection, and decreased after 24 and 48 h. The serum levels of IL-8 were higher than those of animals injected with saline solution at all three time periods, and were higher than those of animals injected with TL at 6 and 24 h. The serum VEGF levels in the SN group were significantly greater than those in the control group or in animals injected with saline solution.

Systemic Inflammatory Effects During the Acute Phase of Experimental Pleurodesis in Rabbits: IL-8

Pleural Fluid Volume: The pleural fluid volume was significantly greater after the intrapleural injection of SN than it was after the intrapleural injection of TL at each time point (Table 1). The amount of pleural fluid tended to increase with time in both groups.
IL-8: There were detectable levels of IL-8 in the pleural fluid after the intrapleural injection of both TL and SN. The highest level of pleural fluid IL-8 occurred in the SN group 6 h after injection, and this level was significantly higher than the levels occurring at 24 or 48 h after SN injection or at any time after the injection of TL (Table 2). The pleural fluid levels of IL-8 were comparable to those in serum, except for the level 6 h after SN injection, which was significantly higher than the serum level (Table 2).

Systemic Inflammatory Effects During the Acute Phase of Experimental Pleurodesis in Rabbits: Pleural Fluid

Systemic Inflammatory Effects During the Acute Phase of Experimental Pleurodesis in Rabbits: Pleural FluidLDH: The intrapleural injection of SN, but not TL or saline solution, led to a short-term increase in serum LDH levels. The mean serum LDH level was significantly higher 6 h after the injection of SN (540 ± 215 IU/L) than after the injection of TL (300 ± 91 IU/L) or saline solution (238 ± 150 IU/L), or compared to the levels in the controls (217 ± 84 IU/L). The increase in the serum LDH level following SN injection had disappeared by 24 and 48 h (Fig 3).

Systemic Inflammatory Effects During the Acute Phase of Experimental Pleurodesis in Rabbits: Cytokines Analysis

IL-8 (OptEIA, rabbit IL-8 set; Pharmingen; San Diego, CA) and VEGF (R&D Systems; Minneapolis, MN) were measured by enzyme-linked immunosorbent assay according to the manufacturers’ directions. Quantification of IL-8 and VEGF was done by comparison of the optical density in the enzyme-linked immunosorbent assay reader (Power Wave; Bio-Tek; Winooski, VT) using a 450-nm filter with the optical density of controls.

Systemic Inflammatory Effects During the Acute Phase of Experimental Pleurodesis in Rabbits: Reagents

Systemic Inflammatory Effects During the Acute Phase of Experimental Pleurodesis in Rabbits: ReagentsThe animals were killed with a lethal injection of pentobarbital (USP Pharmacy). Immediately before the pentobarbital injection, a blood sample from each animal was collected for comparison with normal blood parameters from noninjected rabbits. After death, the animals were exsanguinated by aortic section through a middle abdominal incision, and a 21-gauge needle was inserted through the diaphragm to aspirate the fluid. After the fluid was aspirated, the thoracic cavity was opened and grossly inspected for the presence of TL. Animals injected with saline solution were used as benign noninflammatory controls. Blood samples were collected from a group of six noninjected rabbits as controls on the measurements in the blood of the injected animals. The study was approved by the Ethics Committee of the Heart Institute (InCor), University of Sao Paulo Medical School, which oversees research involving both animals and humans.

Systemic Inflammatory Effects During the Acute Phase of Experimental Pleurodesis in Rabbits: Pleural Injection

SN was one of the first agents used for pleurodesis in concentrations varying from 1 to 10% and had a success rate of 75 to 90%. In a rabbit model with normal pleura, the intrapleural injection of 0.5% SN produced a pleurodesis similar to that produced by 35 mg/kg tetracycline and was superior to that induced by TL slurry, 400 mg/kg. Of concern was the possibility that, due to its intense local caustic effect, SN could produce lung damage. However, in a subsequent 1-year follow-up study, SN induced only minimal microscopic lung damage that decreased after 2 weeks, and was similar to that produced by TL after 21 days.

Systemic Inflammatory Effects During the Acute Phase of Experimental Pleurodesis in Rabbits

Systemic Inflammatory Effects During the Acute Phase of Experimental Pleurodesis in RabbitsPleurodesis is routinely used for the treatment of recurrent malignant pleural effusions. Many agents have been used to produce a pleural symphysis, including silver nitrate (SN), quinacrine, tetracycline and its derivatives doxycycline and minocycline, bleomycin, Corynebacterium parvum, and talc (TL), with different degrees of success. Therapy with SN, which was one of the first agents used to control recurrent pneumothorax, was abandoned apparently because it caused intense pain. The antimalarial agents, particularly quinacrine, are known to induce fever and multiple pleural loculationsA Tetracycline is no longer commercially available and has been replaced mainly by doxycycline, which also causes intense pain. Bleomycin, an antineoplastic agent, was once extensively used, but it is expensive and did not induce pleurodesis in rabbits. C parvum, used mostly in Europe, also was abandoned because its commercial production was stopped.

Thrombin, Inflammation, and Cardiovascular Disease: Conclusions

Thrombin, Inflammation, and Cardiovascular Disease: ConclusionsThis statistical association may be mediated by the key proinflammatory cytokine (also an adipokine) TNF-a, which is a so-called first-wave cytokine influencing IL-6 production, as well as many other cellular functions. TNF-a receptor (TNFR) I signals programmed cell death, while TNFR II may signal survival or proliferation through cytoplasmic TNFR-associated proteins, which can both negatively regulate apoptosis and positively promote survival. Although the role (if any) of circulating TNF-a in humans remains uncertain, TNF-a induces insulin resistance in tissue culture and in animal models.’ Plasma levels are also elevated in the metabolic syndrome, and are associated with insulin resistance in humans. fully

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