In vitro hemo- and cytocompatibility of bacterial nanocelluose small diameter vascular grafts: Impact of fabrication and surface characteristics.

OBJECTIVE: There is an increasing need for small diameter vascular grafts with superior host hemo- and cytocompatibilities, such as low activation of platelets and leukocytes. Therefore, we aimed to investigate whether the preparation of bacterial nanocellulose grafts with different inner surfaces has an impact on in vitro host cytocompatibility. METHODS: We have synthesized five different grafts in a bioreactor, namely open interface surface (OIS), inverted (INV), partially air dried (PAD), surface formed in air contact (SAC) and standard (STD) that were characterized by a different surface roughness. The grafts (length 55 mm, inner diameter 5 mm) were attached to heparinized polyvinyl chloride tubes, loaded with human blood and rotated at 37°C for 4 hours. Then, blood was analyzed for frequencies of cellular fractions, oxidative products, soluble complement and thrombin factors. The results were compared to clinically approved grafts made of polyethylene terephthalate and expanded polytetrafluoroethylene. Additionally, blood platelets were labelled with 111Indium-oxine to visualize the distribution of adherent platelets in the loop by scintigraphy. RESULTS: SAC nanocellulose grafts with the lowest surface roughness exhibited superior performance with <10% leukocyte and <50% thrombocyte loss in contrast to other grafts that exhibited >65% leukocyte and >90% thrombocyte loss. Of note, SAC nanocellulose grafts showed lowest radioactivity with scintigraphy analyses, indicating reduced platelet adhesion. Although the levels of reactive oxygen species and cell free DNA did not differ significantly, the levels of thrombin-antithrombin complexes were lowest in SAC grafts. However, all nanocellulose grafts exhibited enhanced complement activation. CONCLUSION: The systematic variation of the inner surfaces of BNC vascular grafts significantly improves biocompatibility. Especially, SAC grafts exhibited the lowest loss of platelets as well as leukocytes and additionally significantly diminished activation of the coagulation system. Further animal studies are needed to study in vivo biocompatibilities.

Time course and local distribution of skin exposure of hand and fingers from [68Ga]Ga-DOTA-NOC synthesis using a self-shielded module.

AIM: The study examined the local dose distribution as well as the time course of skin exposure of hand and fingers from [68Ga]Ga-DOTA-NOC synthesis using a self-shielded synthesis module. METHODS: A compact calibrated electronic dosimeter (ED) with a miniaturized probe was used for real-time measurements of skin dose equivalent Hp (0.07) (reference point: left and right index finger). A time resolved assessment of exposure during radiotracer production was performed. Additionally, thermoluminescence dosimeters (TLD) were used to determine local dose distribution for five different positions (e. g. fingertips). Cumulated Hp (0.07) estimated by ED was analysed and correlated with the measurements obtained by a TLD positioned close to the ED. RESULTS: The cumulative skin exposure from the production process measured by ED, was 74.7 ±â€Š32.7 µSv/GBq and 40.1 ± 14.3 µSv/GBq for the right and left hand, respectively. The exposure recorded by the ED was in the average 19.4 % ±â€Š40.0 % (median = 21.3 %) lower compared to the results from TLD. Highest exposure was recorded during synthesis (guided hand: 24.5 ±â€Š12.2 µSv/GBq) and measuring of product yield including preparation of probes for quality control (guided hand: 36.1 ±â€Š12.7 µSv/GBq). The highest local exposure was measured by a TLD close to the tip of the index finger of the guiding hand (range: 773-1257 µS/GBq). CONCLUSION: The chosen methodology using ED, proved to be a good concept for identifying procedure steps with an increased exposure level and to determine the time course of skin exposure and to identify procedure steps for further optimization of handling. Furthermore, miniaturized electronic dosimeters may be used for online surveillance of local exposure rates at hands and fingers.

Superficial skin cancer therapy with Y-90 microspheres: A feasibility study on patch preparation.

BACKGROUND: Radiation therapy using beta particles is an interesting treatment for very superficial skin lesions. Due to their low penetration in tissue and rapid dose fall-off, beta particles can protect underlying bony structures and surrounding healthy tissue while irradiating the skin tumor. In the current work, a simple method for the fabrication of a radioactive patch for use in skin cancer therapy based on a beta-emitting isotope is presented. MATERIALS AND METHODS: The beta radiation sources were Y-90 microspheres currently used for catheter-based radioembolization of unresectable liver tumors. The microspheres were filtered through a syringe filter to trap them on the cellulose nitrate paper of the filter and create a radioactive patch. In the current study, to avoid the need for a hot laboratory, the experiment was done using nonradioactive microspheres. An optical microscope was used to verify the distribution of the particles on the filter paper. RESULTS: Visual evaluation of the patches showed that using the proposed method, therapeutic skin patches with a fairly uniform distribution of microspheres can be created. CONCLUSION: The proposed simple method may be used in creating radiotherapeutic patches using Y-90 microspheres for radiation therapy of thin skin lesions located close to sensitive structures.

Impact of heme and heme degradation products on vascular diameter in mouse visual cortex.

BACKGROUND: Delayed cerebral vasospasm is the most common cause of mortality and severe neurological impairment in patients who survive subarachnoid hemorrhage. Despite improvements in the field of diagnostic imaging, options for prevention and medical treatment-primarily with the calcium channel antagonist nimodipine or hemodynamic manipulations-are insufficient. Previous studies have suggested that heme and bilirubin oxidation end products, originating from degraded hemoglobin around ruptured blood vessels, are involved in the development of vasospasm by inhibiting large conductance BKC a potassium channels in vascular smooth muscle cells. In this study, we identify individual heme degradation products regulating arteriolar diameter in dependence of BKC a channel activity. METHODS AND RESULTS: Using differential interference contrast video microscopy in acute brain slices, we determined diameter changes of intracerebral arterioles in mouse visual cortex. In preconstricted vessels, the specific BKC a channel blockers paxilline and iberiotoxin as well as iron-containing hemin caused vasoconstriction. In addition, the bilirubin oxidation end product Z-BOX A showed a stronger vasoconstrictive potency than its regio-isomer Z-BOX B. Importantly, Z-BOX A had the same vasoconstrictive effect, independent of its origin from oxidative degradation or chemical synthesis. Finally, in slices of Slo1-deficient knockout mice, paxilline and Z-BOX A remained ineffective in changing arteriole diameter. CONCLUSIONS: We identified individual components of the oxidative bilirubin degradation that led to vasoconstriction of cerebral arterioles. The vasoconstrictive effect of Z-BOX A and Z-BOX B was mediated by BKC a channel activity that might represent a signaling pathway in the occurrence of delayed cerebral vasospasm in subarachnoid hemorrhage patients.

Total synthesis and detection of the bilirubin oxidation product (Z)-2-(3-ethenyl-4-methyl-5-oxo-1,5-dihydro-2H-pyrrol-2-ylidene)ethanamide (Z-BOX A).

The selective total synthesis of the pure Z-isomer of BOX A (8a), a product of oxidative heme degradation with significant physiological impact, was achieved in four to six steps starting from 3-bromo-4-methylfuran-2,5-dione (1). Z-BOX A forms a strong hydrogen bridge framework in the crystalline state. LC-MS techniques allow identification and characterization of isomeric forms of BOX A.