A study of the reaction of lymphatic endothelium and of leucocytes, in the tadpole's tail, toward injected fat

Clark, Eliot R.; Clark, Eleanor Linton

doi:10.1002/aja.1000210305

Cited by 24 publications

(4 citation statements)

References 15 publications

(6 reference statements)

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“…Goldmann [1933], using special methods, was unable to find fat in lymphocytes although he identified it in all the other types of leucocytes. Again, in the experiments of Clark & Clark [1917], the cells which took up the fat droplets were never identified as lymphocytes or even as leucocytes. Although Schafer attributed fat transport activities to lymph corpuscles, it does not appear certain from his drawings that true lymphocytes were engaged in this activity at all.…”

Section: Discussionmentioning

confidence: 99%

The role of leucocytes in fat absorption

Leach¹

1938

The Journal of Physiology

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Section: Discussionmentioning

confidence: 99%

The role of leucocytes in fat absorption

Leach¹

1938

The Journal of Physiology

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“…The trafficking of foreign material, such as oil-based formulations, via lymphatic vessels has been known for many years (Clark and Clark 1917). Such trafficking can be mediated by antigen presenting cells or as passive absorption (Ramot et al 2009).…”

Section: Weeksmentioning

confidence: 99%

Toxicity and Toxicokinetic Study of Subcutaneously Administered RPh201 in Minipigs

et al. 2018

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Mastic gum extracts are widely used as herbal remedies and are being tested for several clinical indications. Nevertheless, information on their safety is limited. RPh201 is an extract of the mastic gum, formulated and stabilized in a proprietary method, which is being developed as a novel drug candidate for neurological indications. The aim of this study was to assess the systemic toxic potential of RPh201, administered twice weekly by subcutaneous injections to minipigs, after 39 weeks of administration followed by a recovery period of 6 weeks. No clinical or dose-related signs were observed, but treatment-related findings were seen at the injection sites of the high-dose animals, composed of abscesses, chronic inflammation, and subcutaneous fibrosis. Abscesses >30 mm in size, graded as marked severity, were confined to the high-dose group and were considered as adverse. Minimal-slight subcutaneous and lymph nodes abscesses seen in control, low, and intermediate doses, related to the vehicle (cottonseed oil), were not considered as adverse. Additionally, minimal-to-slight cystic spaces or vacuolation related to the vehicle were observed in the skin, lymph nodes, kidney, and lungs. These findings were considered not to be adverse. The no-observed-adverse-effect level was considered to be 12.5 mg/kg/occasion.

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“…The lymphatic vessels may constitute one possible channel. That lymphatic vessels react by sending sprouts that grow toward injected olive oil has been known for many years (Clark and Clark 1917). Supporting that finding is the discovery of silicone in regional lymph nodes after SC administration in mice (Ben-Hur et al 1967).…”

mentioning

confidence: 99%

“…This trafficking through the lymphatic system may be mediated by antigen presenting cells (APCs), such as Langerhans cells residing in the dermis. The reaction of cells of the immune system to engulf olive oil in the skin was documented long ago (Clark and Clark 1917), and their migratory path was followed after injection of AK-5 tumor cells, which were engulfed by APCs, delivered to regional lymph nodes, and moved from there to the peritoneum (Mitra et al 2004), a process that took a total of three days. Following these results, researchers suggested that the peritoneum functions as an organ with lymphoid characteristics, where the APCs perform their antigen presentation function and elicit an immune reaction (Mitra et al 2004).…”

mentioning

confidence: 99%

Subcutaneous and Intraperitoneal Lipogranulomas Following Subcutaneous Injection of Olive Oil in Sprague-Dawley Rats

Ramot

Ben-Eliahu²,

Kagan

et al. 2009

Toxicol Pathol

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Olive oil is commonly employed as a solubilizing agent for lipophilic materials in preclinical studies in rodents. Here we report that following subcutaneous (SC) injection of olive oil to Sprague-Dawley (SD) rats, local SC lipogranulomas formed, which were associated with an unusual location of the same changes in the peritoneum. Macroscopically, multifocal white spots were found over the liver and mesentery. Histologically, lipid granulomas were seen in the SC injection site, as well as on the capsular or serosal surface of the abdominal organs. No abnormal clinical signs were noted except for swelling at the injection site. The olive oil may have reached the peritoneal cavity from the SC tissue passively via the lymphatic vessels or actively after engulfment by antigen-presenting cells via the lymphatic or blood vessels. These findings are of particular importance for drug safety assessments, as the occurrence of lipogranulomas in locations distant from the site of administration may lead to misinterpretation of histological results. We suggest that these aberrations may be induced by the administration of olive oil as a vehicle.

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A study of the reaction of lymphatic endothelium and of leucocytes, in the tadpole's tail, toward injected fat

Cited by 24 publications

References 15 publications

The role of leucocytes in fat absorption

The role of leucocytes in fat absorption

Toxicity and Toxicokinetic Study of Subcutaneously Administered RPh201 in Minipigs

Subcutaneous and Intraperitoneal Lipogranulomas Following Subcutaneous Injection of Olive Oil in Sprague-Dawley Rats

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