Bhavani, S. | Search bioRxiv

bioRxiv2023

Comparative evaluation of straight and curved extension dialysis catheters for continuous renal replacement therapy in dogs with acute kidney injury

A patent dual lumen dialysis catheter is one of the basic requirements for efficient extracorporeal (EC) therapy. The objective of this study was to measure resistance to blood flow offered by straight and curved extension dual lumen dialysis catheters used for continuous renal replacement therapy (CRRT). Twenty dogs suffering from acute kidney injury (AKI) were subjected to CRRT. The dogs were allocated randomly to Group-I (Curved extension catheter, n=12) or Group-II (Straight extension catheter, n=8), based on the type of dual-lumen catheter used in CRRT. The catheter outflow and inflow pressures were recorded at blood pump speeds of 50 mL/min and 99-100 mL/min. Data were tested for normality and differences in mean inflow and outflow catheter resistances were evaluated for statistical significance using independent samples t tests. Straight extension catheters offered lower inflow resistance than curved extension catheters at both 50 mL/min (41.50 {+/-} 5.84 mm Hg and 63.75 {+/-} 6.88 mm Hg, respectively; P=0.03) and 99-100 mL/min (63.00 {+/-} 8.11 mm Hg and 86.92 {+/-} 7.02 mm Hg, respectively; P=0.04) blood flow rates. Straight extension catheters also offered lower outflow resistance than curved catheters at 99-100 mL/min (-94.12 {+/-} 7.91 mm Hg and -128.25 {+/-} 7.56 mm Hg, respectively; P=0.01; the negative signs only indicate the direction of blood flow). These findings suggest that straight extension dual lumen dialysis catheters would likely perform better than the curved model in extracorporeal renal replacement therapy.

pathology↗

bioRxiv2022

A novel maxillofacial technique to deliver drugs to the visual pathway, the optic nerve and the retina using the glymphatic system.

The blood neural barriers are formidable barriers that prevent delivery of drugs into the eye and the brain. Currently, large biologics are used for treating many diseases of the eye and the brain. But the blood retinal barrier and the blood brain barrier prevent entry of these useful drugs into the eye and the brain respectively. Hence, there is a need for a drug delivery technique to bypass these natural barriers. Bevacizumab (Avastin) is a full length humanized monoclonal antibody with a molecular weight of 149kda. It binds to circulating vascular endothelial growth factor A and prevents interaction with vascular endothelial growth receptors. This results in blocking endothelial response and tumor vascularization. Bevacizumab is used to prevent choroidal neovascularization in age related macular degeneration and to prevent retinal neovascularization in diabetic retinopathy. It is also used for treating certain types of brain cancer. But it crosses neither the blood retinal barrier nor the blood brain barrier. This in vivo mouse study assessed the delivery of a commercial formulation of bevacizumab into the retina of mice using different ocular techniques like topical drops, subconjunctival injection, intravitreal injection and a novel maxillofacial technique. The objective was to assess whether the novel maxillofacial drug delivery technique could deliver drugs into the retina and to compare the efficacy of the maxillofacial technique with the mentioned ocular techniques. The distribution of bevacizumab was further compared with retinoschisin which is a small protein with a molecular weight of 24kda. Intravitreal injection and maxillofacial technique were effective in delivering drugs into the retina. In addition, the maxillofacial technique could target the brain including regions involved in the visual pathway and the optic nerve. The glymphatic pathway could also be targeted for drug delivery. Drug was also detected in the contralateral optic nerve and retina. Based on our study findings, we propose a new concept to explain the presence of the drug in the contralateral eye. We propose that after maxillofacial drug delivery, early distribution of the drug can occur in the CSF at the optic chiasma from the brain via the glymphatic system. In the case of the intravitreal injection, the drug from the experimental eye may be cleared through the glymphatic pathway of the ipsilateral optic nerve into the CSF surrounding the nerve. The crossover of the ipsilateral optic nerve fibers at the optic chiasma can result in further distribution of the drug in the CSF at the optic chiasma. From the region of the optic chiasma, the drug can distribute into the CSF surrounding the contralateral optic nerve. The drug can be then distributed into the contralateral optic nerve through the glymphatic pathway and be delivered into the contralateral eye. The drug can be further cleared into the aqueous of the contralateral eye through the anterior clearance pathway.

neuroscience↗