scholarly journals THE EFFECT OF UNFRACTIONATED HEPARIN ON LYMPHATIC DRAINAGE OF TISSUES AND PHARMACOKINETICS OF CEFOTAXIM

2019 ◽  
Vol 25 (3) ◽  
pp. 181-184
Author(s):  
German V. Kukushkin ◽  
M. V Zhuravleva ◽  
L. P Sviridkina ◽  
D. E Yurov

Over the past decades, methods of targeted delivery of drugs to target tissues through the lymphatic system have been intensively developed, which makes it possible to create and maintain adequate concentrations of drugs. It has special meaning and impotence during the therapy antibiotic therapy of infectious and inflammatory processes. In this regard, the experimental study of pharmacological properties of drugs that enhance lymphatic drainage of tissues and at the same time promote the transport of antibiotics into the lymphatic system has natural interest. We studied the effect of unfractionated heparin sodium on lymphatic flow rate in tissues, the level of the β-lactam antibiotic cefotaxime in rabbit and mouse blood plasma and its concentration in mouse liver and intestinal tissues in experiments. Heparin sodium proved to be effective in stimulating lymphatic flow and facilitating endolymphatic delivery of the antibiotic. The administration of cefotaxime after an injection of heparin sodium led to the increased concentration of the antibiotic in rabbit blood plasma at all time points of the study (in an hour and a half and in 3 hours, in four and a half hours and in 6 hours, in 8, 12 and 24 hours), as well as the increased antibiotic level in mouse blood plasma and intestinal tissue in an hour and a half and in 24 hours after the injection. The cefotaxime level in liver tissue did not change, while its concentration ratio between liver tissue and blood plasma was falling, which suggests that the hepatic extraction of cefotaxime decreased. Considering the obtained evidence, we can recommend the clinical use of heparin sodium in lymphotropic therapy to facilitate endolymphatic delivery.

2021 ◽  
Vol 104 (1) ◽  
pp. 003685042199848
Author(s):  
Bianca Brix ◽  
Gert Apich ◽  
Andreas Rössler ◽  
Sebastian Walbrodt ◽  
Nandu Goswami

Lymphedema is manifested as a chronic swelling arising due to stasis in the lymphatic flow. No cure is currently available. A non-invasive treatment is a 3 week complete decongestive therapy (CDT), including manual lymphatic drainage and compression bandaging to control swelling. As CDT leads to mobilization of several liters of fluid, effects of CDT on hyaluronan clearance (maker for lymphatic outflow), volume regulating hormones, total plasma protein as well as plasma density, osmolality and selected electrolytes were investigated. In this pilot study, we assessed hyaluronan and volume regulating hormone responses from plasma samples of nine patients (three males, six females, aged 55 ± 13 years) with lower limb lymphedema stage II-III, before - and after - CDT. A paired non-parametric test (Wilcoxon) was used to assess hormonal and plasma volume changes. Correlation was tested using Spearman’s correlation. The main findings of this novel study are that lymphedema patients lost volume and weight after therapy. Hyaluronic acid did not significantly change pre- compared to post-CDT. Aldosterone increased significantly after therapy, while plasma renin activity increased, but not significantly. Plasma total protein, density, osmolality and sodium and chloride did not show differences after CDT. To our knowledge, no study has previously investigated the effects of CDT on volume regulating hormones or electrolytes. To identify the time-course of volume regulating hormones and lymphatic flow changes induced by CDT, future studies should assess these parameters serially over 3 weeks of therapy.


2017 ◽  
Vol 2017 ◽  
pp. 1-8
Author(s):  
Ann-Christin Niehoff ◽  
Tim Klasen ◽  
Rebecca Schmidt ◽  
Daniel Palmes ◽  
Cornelius Faber ◽  
...  

Secondary lymphedema accompanied with strong restrictions in quality of life is still major side effects in cancer therapy. Therefore, dedicated diagnostic tools and further investigation of the lymphatic system are crucial to improve lymphedema therapy. In this pilot study, a method for quantitative analysis of the lymphatic system in a rat model by laser ablation (LA) with inductively coupled plasma mass spectrometry imaging (ICP-MSI) is presented. As a possible lymph marker, thulium(III)(1R,4R,7R,10R)-α,α′,α′′,α′′′-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (Tm-DOTMA) is introduced and compared to the clinically used magnetic resonance imaging contrast agent gadolinium(III)2,2′,2′′-(10-((2R,3S)-1,3,4-trihydroxybutan-2-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate (Gd-DO3A-butrol). Gadobutrol functioned as standard contrast media in MRI lymphangiography to detect lymphatic flow qualitatively. Thus, Tm-DOTMA was investigated as lymphatic marker to detect lymphatic flow quantitatively. Both contrast agents were successfully used to visualize the lymphatic flow in successive lymph nodes in LA-ICP-MS due to lower limits of detection compared to MRI. Furthermore, the distribution of contrast agents by multicolored imaging showed accumulation in specific areas (sectors) of the lymph nodes after application of contrast agents in different areas.


2007 ◽  
Vol 30 (8) ◽  
pp. 1365-1368 ◽  
Author(s):  
Shuichi Kusano ◽  
Atsuko Ootani ◽  
Shinobu Sakai ◽  
Naoko Igarashi ◽  
Atsuko Takeguchi ◽  
...  

2002 ◽  
Vol 282 (3) ◽  
pp. H850-H854 ◽  
Author(s):  
J. Job Faber ◽  
Debra F. Anderson

Swallowing of amniotic fluid and lung fluid inflow were eliminated in 10 chronically instrumented fetuses. The urachus was ligated, and fetal was urine drained to the outside. At the beginning and the end of 21 experiments of 66 ± 5 (SE) h duration, all amniotic fluid was temporarily drained to the outside for volume measurement and sampling. Amniotic fluid osmolalities and oncotic pressures were experimentally controlled. Amniochorionic absorption of amniotic fluid depended strongly on the osmolality difference between amniotic fluid and fetal plasma ( P< 0.001), but at zero osmolality difference there still was a mean absorption rate of 23.8 ± 4.7 (SE) ml/h ( P < 0.001). Absorption was unaffected by the protein concentration difference between amniotic fluid and fetal plasma, but infused bovine albumin in the amniotic fluid was absorbed at a rate of 1.8 ± 0.4 g/h ( P < 0.001), corresponding to a volume flow of fluid of 33.8 ± 6.1 ml/h ( P < 0.001). Fluid absorption in the amniochorion is driven in part by crystalloid osmotic pressure, but about 25 ml/h is absorbed by a path that is permeable to protein. That path has the physiological characteristics of lymphatic drainage, although no anatomic basis is known to exist for a lymphatic system in the amniochorion.


2020 ◽  
Vol 37 (03) ◽  
pp. 250-262 ◽  
Author(s):  
Claus Christian Pieper

AbstractNovel lymphatic imaging and interventional techniques are increasingly used in the diagnostic workup and treatment of pathologies of the central lymphatic system and have opened a new field of interventional radiology. The mainstay of lymphatic imaging today is magnetic resonance lymphangiography (MRL). It provides information on the anatomy of the central lymphatic system, lymphatic flow, as well as lymphatic pathologies and therefore is a valuable tool for treatment planning. There are two techniques to perform contrast-enhanced MRL: nodal dynamic contrast-enhanced MRL (nodal DCE-MRL) and interstitial transpedal MRL (tMRL). Nodal DCE-MRL yields superior information on lymphatic flow dynamics and is therefore best suited for suspected lymphatic flow pathologies and lymphatic malformations. tMRL is a technically simpler alternative for central lymphatic visualization without the need for sonographically guided lymph node cannulation. This review article describes current MRL techniques with a focus on contrast-enhanced MRL, their specific advantages, and possible clinical applications in patients suffering from pathologies of the central lymphatic system.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ashley C. Bolte ◽  
Arun B. Dutta ◽  
Mariah E. Hurt ◽  
Igor Smirnov ◽  
Michael A. Kovacs ◽  
...  

Abstract Traumatic brain injury (TBI) is a leading global cause of death and disability. Here we demonstrate in an experimental mouse model of TBI that mild forms of brain trauma cause severe deficits in meningeal lymphatic drainage that begin within hours and last out to at least one month post-injury. To investigate a mechanism underlying impaired lymphatic function in TBI, we examined how increased intracranial pressure (ICP) influences the meningeal lymphatics. We demonstrate that increased ICP can contribute to meningeal lymphatic dysfunction. Moreover, we show that pre-existing lymphatic dysfunction before TBI leads to increased neuroinflammation and negative cognitive outcomes. Finally, we report that rejuvenation of meningeal lymphatic drainage function in aged mice can ameliorate TBI-induced gliosis. These findings provide insights into both the causes and consequences of meningeal lymphatic dysfunction in TBI and suggest that therapeutics targeting the meningeal lymphatic system may offer strategies to treat TBI.


2013 ◽  
Vol 449 (1) ◽  
pp. 87-89 ◽  
Author(s):  
E. V. Rudakova ◽  
G. F. Makhaeva ◽  
T. G. Galenko ◽  
A. Yu. Aksinenko ◽  
V. B. Sokolov ◽  
...  

2015 ◽  
Vol 59 (6) ◽  
pp. 3271-3280 ◽  
Author(s):  
Luiz Francisco Rocha e Silva ◽  
Karla Lagos Nogueira ◽  
Ana Cristina da Silva Pinto ◽  
Alejandro Miguel Katzin ◽  
Rodrigo A. C. Sussmann ◽  
...  

ABSTRACT4-Nerolidylcatechol (1) is an abundant antiplasmodial metabolite that is isolated fromPiper peltatumroots.O-Acylation orO-alkylation of compound1provides derivatives exhibiting improved stability and significantin vitroantiplasmodial activity. The aim of this work was to study thein vitroinhibition of hemozoin formation, inhibition of isoprenoid biosynthesis inPlasmodium falciparumcultures, andin vivoantimalarial activity of several 4-nerolidylcatechol derivatives. 1,2-O,O-Diacetyl-4-nerolidylcatechol (2) inhibitedin vitrohemozoin formation by up to 50%. In metabolic labeling studies using [1-(n)-3H]geranylgeranyl pyrophosphate, diester2significantly inhibited the biosynthesis of isoprenoid metabolites ubiquinone8, menaquinone4, and dolichol12in cultures ofP. falciparum3D7. Similarly, 2-O-benzyl-4-nerolidylcatechol (3) significantly inhibited the biosynthesis of dolichol12.P. falciparumin vitroprotein synthesis was not affected by compounds2or3. At oral doses of 50 mg per kg of body weight per day, compound2suppressedPlasmodium bergheiNK65 in infected BALB/c mice by 44%. Thisin vivoresult for derivative2represents marked improvement over that obtained previously for natural product1. Compound2was not detected in mouse blood 1 h after oral ingestion or in mixtures with mouse blood/blood plasmain vitro. However, it was detected afterin vitrocontact with human blood or blood plasma. Derivatives of 4-nerolidylcatechol exhibit parasite-specific modes of action, such as inhibition of isoprenoid biosynthesis and inhibition of hemozoin formation, and they therefore merit further investigation for their antimalarial potential.


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