Role of Lymphatic System on Snake Venom Absorption

Paniagua, Dayanira; Vergara, Irene; Boyer, Leslie V.; Alagón, Alejandro

doi:10.1007/978-94-007-6410-1_10

Cited by 12 publications

(30 citation statements)

References 71 publications

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“…Nevertheless, we have to consider the difference between the local effects of these two venoms since neurotoxic coral snake venom does not cause local damage, including injury of the lymphatic system with lymphedema, or a delayed uptake from tissue injury, as does V. ammodytes venom [ 13 ]. For a V. ammodytes bite, the lymphatic pathway could be effective if the antivenom is given intramuscularly since large antivenom macromolecules can be absorbed only in lymphatic capillaries with an incomplete basal lamina, and venom neutralisation can happen in larger lymphatic ducts and local lymphatic nodes before it reaches the bloodstream [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Intravenous Vipera berus Venom-Specific Fab Fragments and Intramuscular Vipera ammodytes Venom-Specific F(ab’)2 Fragments in Vipera ammodytes-Envenomed Patients

Kurtović

Karabuva

Grenc

et al. 2021

Toxins

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Vipera ammodytes (V. ammodytes) is the most venomous European viper. The aim of this study was to compare the clinical efficacy and pharmacokinetic values of intravenous Vipera berus venom-specific (paraspecific) Fab fragments (ViperaTAb) and intramuscular V. ammodytes venom-specific F(ab’)2 fragments (European viper venom antiserum, also called “Zagreb” antivenom) in V.ammodytes-envenomed patients. This was a prospective study of V.ammodytes-envenomed patients that were treated intravenously with ViperaTAb or intramuscularly with European viper venom antiserum that was feasible only due to the unique situation of an antivenom shortage. The highest venom concentration, survival, length of hospital stay and adverse reactions did not differ between the groups. Patients treated with intravenous Fab fragments were sicker, with significantly more rhabdomyolysis and neurotoxicity. The kinetics of Fab fragments after one or more intravenous applications matched better with the venom concentration in the early phase of envenomation compared to F(ab’)2 fragments that were given intramuscularly only on admission. F(ab’)2 fragments given intramuscularly had 25-fold longer apparent total body clearance and 14-fold longer elimination half-time compared to Fab fragments given intravenously (2 weeks vs. 24 hours, respectively). In V.ammodytes-envenomed patients, the intramuscular use of specific F(ab’)2 fragments resulted in a slow rise of antivenom serum concentration that demanded their early administration but without the need for additional doses for complete resolution of all clinical signs of envenomation. Intravenous use of paraspecific Fab fragments resulted in the immediate rise of antivenom serum concentration that enabled their use according to the clinical progress, but multiple doses might be needed for efficient therapy of thrombocytopenia due to venom recurrence, while the progression of rhabdomyolysis and neurotoxic effects of the venom could not be prevented.

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Section: Discussionmentioning

confidence: 99%

Intravenous Vipera berus Venom-Specific Fab Fragments and Intramuscular Vipera ammodytes Venom-Specific F(ab’)2 Fragments in Vipera ammodytes-Envenomed Patients

Kurtović

Karabuva

Grenc

et al. 2021

Toxins

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“…CTX is a peptide toxin found in the venom of the death stalker scorpion (Leiurus quinquestriatus). Studies have shown that toxins can be absorbed through the lymphatics (36). Toxins absorbed in the lymph pool act as a depository providing sustained release of toxin back into the blood stream yielding a complex absorption process (37).…”

Section: Discussionmentioning

confidence: 99%

Time-Resolved MRI Assessment of Convection-Enhanced Delivery by Targeted and Nontargeted Nanoparticles in a Human Glioblastoma Mouse Model

et al. 2019

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Convection-enhanced delivery (CED) provides direct access of infusates to brain tumors, however, clinical translation of this technology has not been realized because of the inability to accurately visualize infusates in real-time and lack of targeting modalities against diffuse cancer cells. In this study we use time-resolved MRI to reveal the kinetics of CED processes in a glioblastoma (GBM) model using iron oxide nanoparticles (NPs) modified with a glioma targeting ligand, chlorotoxin (CTX). Mice bearing orthotopic human GBM tumors were administered a single dose of targeted CTX-conjugated NP (NPCP-CTX) or non-targeted NP (NPCP) via CED. High resolution T2weighted, T2*-weighted and quantitative T2 MRI was utilized to image NP delivery in real-time and determine the volume of distribution (VD) of NPs at multiple time points over the first 48 h post-CED. GBM specific targeting was evaluated by flow cytometry and intracellular NP localization by histological assessment. NPCP-CTX produced a V D of 121 ± 39 mm 3 at 24 h, a significant increase compared to NPCP, while exhibiting GBM specificity and localization to cell nuclei. Notably, CED of NPCP-CTX resulted in a sustained expansion of VD well after infusion, suggesting a possible active transport mechanism which was further supported by the presence of NPs in endothelial and red blood cells. In summary, we show that time-resolved MRI is a suitable modality to study CED kinetics and CTX-mediated CED facilitates extensive distribution of infusate and specific targeting of tumor cells.

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“…When TA was injected into the posterior part of the vitreous during vitrectomy, the TA particles adhered exclusively to the anterior surfaces of the BPM and Martegiani area, presumably due to their feathery structure ( Figure 1 b) [ 5 ]. Furthermore, the surface appearance of the BPM described by Worst et al [ 5 ] seems to resemble that of the initial lymphatics associated with the anchoring filaments [ 94 ]. Assuming that the surfaces of the BS and the BPM consist of an initial lymphatic-like structure, excess vitreous fluid might enter these tissues via increased intraocular pressure (IOP) and movement of the vitreous.…”

Section: Discussionmentioning

confidence: 99%

Expression of Lymphatic Markers in the Berger’s Space and Bursa Premacularis

Morishita

Sato

Oosuka

et al. 2021

IJMS

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We previously reported that the bursa premacularis (BPM), a peculiar vitreous structure located above the macula, contains numerous cells expressing markers of lymphatic endothelial cells, such as podoplanin and LYVE-1. Herein, we examined the expression of lymphatic markers in the Berger’s space (BS), BPM, and vitreous core (VC). BS, BPM, and VC specimens were selectively collected in macular hole and epiretinal membrane patients during vitrectomy and were then immunostained with antibodies for podoplanin, LYVE-1, and fibrillin-1 and -2. By visualization using triamcinolone acetonide, the BS was recognized as a sac-like structure with a septum located behind the lens as well as BPM. Those tissues adhered to the lens or retina in a circular manner by means of a ligament-like structure. Immunostaining showed intense expression of podoplanin and LYVE-1 in the BS. Both BS and BPM stained strongly positive for fibrillin-1 and -2. The VC was faintly stained with antibodies for those lymph-node markers. Our findings indicate that both BS and BPM possibly belong to the lymphatic system, such as lymph nodes, draining excess fluid and waste products into lymphatic vessels in the dura mater of the optic nerve and the ciliary body, respectively, via intravitreal canals.

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Role of Lymphatic System on Snake Venom Absorption

Cited by 12 publications

References 71 publications

Intravenous Vipera berus Venom-Specific Fab Fragments and Intramuscular Vipera ammodytes Venom-Specific F(ab’)2 Fragments in Vipera ammodytes-Envenomed Patients

Intravenous Vipera berus Venom-Specific Fab Fragments and Intramuscular Vipera ammodytes Venom-Specific F(ab’)2 Fragments in Vipera ammodytes-Envenomed Patients

Time-Resolved MRI Assessment of Convection-Enhanced Delivery by Targeted and Nontargeted Nanoparticles in a Human Glioblastoma Mouse Model

Expression of Lymphatic Markers in the Berger’s Space and Bursa Premacularis

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