NIR-laser tissue welding in an in vivo guinea pig animal model

Author(s):  
Vidyasagar Sriramoju ◽  
Howard E. Savage ◽  
A. Katz ◽  
Rahul Chakraverty ◽  
Yuri Budansky ◽  
...  
2021 ◽  
Author(s):  
Friedrich Ihler ◽  
Saskia Freytag ◽  
Benedikt Kloos ◽  
Jennifer Lee Spiegel ◽  
Frank Haubner ◽  
...  

2008 ◽  
Vol 22 (6) ◽  
pp. 625-628 ◽  
Author(s):  
Benjamin S. Bleier ◽  
James N. Palmer ◽  
Michael A. Gratton ◽  
Noam A. Cohen

Background One of the challenges in the current expansion of endoscopic sinonasal surgery is the ability to adequately reconstruct the skull base. Laser tissue welding (LTW) uses laser energy coupled to a biological solder to produce tissue bonds with burst thresholds exceeding human intracranial pressure. This technology could be used to reduce the rate of postoperative cerebrospinal fluid (CSF) leak. We performed this study to determine whether LTW can create durable tissue bonds in sinonasal mucosa that support normal wound healing and produce minimal collateral thermal injury. Methods Bilateral maxillary sinus mucosal incisions were made in 20 New Zealand white rabbits and one side was repaired using LTW. Burst pressure thresholds were measured on postoperative days 0, 5, and 15 and were compared with control using a two- way ANOVA and a post hoc Tukey test. Welds were examined histologically for thermal injury, inflammation, and fibroplasia and graded on a 4-point scale by three blinded observers. Results The burst pressures of the LTW group were significantly higher than control on postoperative day 0 (120.85 mm Hg, N = 4, SD = 47.84 versus 7.85 mm Hg, N = 4, SD = 0.78), and day 5 (132.56 mm Hg, N = 8, SD = 24.02 versus 41.7 mm Hg, N = 8, SD = 7.2; p < 0.05). By postoperative day 15 there was no significant difference between LTW (169.64 mm Hg, N = 8, SD = 18.49) and control (160.84 mm Hg, N = 8, SD = 14.16) burst thresholds. There was no evidence of thermal injury to the surrounding tissue in any group as well as no difference between experimental group and control with respect to inflammation or fibroplasia. Conclusion This is the first in vivo study showing that LTW is capable of producing tissue bonds exceeding human intracranial pressure with negligible thermal injury in sinonasal tissue. Welding can be performed endoscopically using a fiberoptic cable and may be useful in CSF leak and skull base repair.


Blood ◽  
1989 ◽  
Vol 74 (2) ◽  
pp. 690-694 ◽  
Author(s):  
BH Becker ◽  
JL Miller

Abstract Previous studies in the guinea pig model system have established a close structural homology between human and guinea pig glycoproteins Ib (GPIb) and IIb/IIIa (GPIIb/IIIa). Moreover, the murine monoclonal antibody (MoAb) PG-1, which recognizes GPIb in guinea pig platelets and megakaryocytes, exerted full inhibition on von Willebrand factor (vWF)- dependent platelet agglutination without inhibiting aggregation induced by ADP, collagen, or thrombin. The present research extends this animal model system to study of the effects on hemostatic function following the in vivo injection of MoAb PG-1 or its F(ab')2 fragments. A hind limb template bleeding time methodology was developed for use in guinea pigs. Normal bleeding time was determined to be 2.7 +/- 0.5 minutes (mean +/- SD), with an observed range of two to four minutes. Platelet counts in these same animals were 501 +/- 82 x 10(3)/microL. After intraperitoneal (IP) injection of busulfan, guinea pigs became increasingly thrombocytopenic. As long as the platelet count remained above approximately 150 x 10(3)/microL, the bleeding time was not more than five minutes; however, further decrease in the platelet count was accompanied by more marked prolongations of the bleeding time. For 14 to 72 hours after IP injection of 1.3 mg/kg intact PG-1 MoAb, a hemorrhagic state was produced with a bleeding time greater than 20 minutes. The platelet count concurrently decreased to approximately 50% of its baseline value but could not be further decreased either by raising the initial PG-1 dosage tenfold or by administering a second, equal dose 24 hours after the initial injection. This finding may reflect a heterogeneity of circulating platelets with respect to GPIb, to Fc receptors, or to an interaction between them. After IP injection of 0.63 to 2.5 mg/kg PG-1 F(ab')2 fragment, platelet counts did not decrease more than 21% below baseline levels in a 72-hour period, and bleeding times never increased by more than one minute over baseline values. Nevertheless, platelets obtained from animals 24 hours after injection of 2.5 mg/kg PG-1 F(ab')2 showed full inhibition of agglutination induced by ristocetin. The response of these platelets to aggregation by asialo-vWF was also severely inhibited as compared with control platelets. PG-1 F(ab')2 produced no effect on aggregation induced by ADP. These studies show that virtually complete functional block of the vWF receptor by F(ab')2 fragments of the anti-GPIb MoAb PG- 1 is not sufficient to produce a hemorrhagic state in the guinea pig animal model system.


2015 ◽  
Vol 24 (6) ◽  
pp. 1541-1552 ◽  
Author(s):  
Haroon Ashraf Parimoo ◽  
Rinku Sharma ◽  
Rajendra Damu Patil ◽  
Vikram Patial

2015 ◽  
Vol 90 (1) ◽  
pp. 392-399 ◽  
Author(s):  
Gary Wong ◽  
Shihua He ◽  
Haiyan Wei ◽  
Andrea Kroeker ◽  
Jonathan Audet ◽  
...  

ABSTRACT Infections with Sudan virus (SUDV), a member of the genus Ebolavirus , result in a severe hemorrhagic fever with a fatal outcome in over 50% of human cases. The paucity of prophylactics and therapeutics against SUDV is attributed to the lack of a small-animal model to screen promising compounds. By repeatedly passaging SUDV within the livers and spleens of guinea pigs in vivo , a guinea pig-adapted SUDV variant (SUDV-GA) uniformly lethal to these animals, with a 50% lethal dose (LD 50 ) of 5.3 × 10 −2 50% tissue culture infective doses (TCID 50 ), was developed. Animals infected with SUDV-GA developed high viremia and died between 9 and 14 days postinfection. Several hallmarks of SUDV infection, including lymphadenopathy, increased liver enzyme activities, and coagulation abnormalities, were observed. Virological analyses and gross pathology, histopathology, and immunohistochemistry findings indicate that SUDV-GA replicates in the livers and spleens of infected animals similarly to SUDV infections in nonhuman primates. These developments will accelerate the development of specific medical countermeasures in preparation for a future disease outbreak due to SUDV. IMPORTANCE A disease outbreak due to Ebola virus (EBOV), suspected to have emerged during December 2013 in Guinea, with over 11,000 dead and 28,000 infected, is finally winding down. Experimental EBOV vaccines and treatments were administered to patients under compassionate circumstances with promising results, and availability of an approved countermeasure appears to be close. However, the same range of experimental candidates against a potential disease outbreak caused by other members of the genus Ebolavirus , such as Sudan virus (SUDV), is not readily available. One bottleneck contributing to this situation is the lack of a small-animal model to screen promising drugs in an efficient and economical manner. To address this, we have generated a SUDV variant (SUDV-GA) that is uniformly lethal to guinea pigs. Animals infected with SUDV-GA develop disease similar to that of SUDV-infected humans and monkeys. We believe that this model will significantly accelerate the development of life-saving measures against SUDV infections.


2020 ◽  
Author(s):  
Antonin C André ◽  
Céline Mulet ◽  
Mark C Anderson ◽  
Louise Injarabian ◽  
Achim Buch ◽  
...  

AbstractShigella spp. are the causative agents of bacillary dysentery or shigellosis, mainly in children living in developing countries. The study of Shigella entire life cycle in vivo and the evaluation of vaccine candidates’ protection efficacy have been hampered by the lack of a suitable animal model of infection (1). None of the ones evaluated so far (mouse, rabbit, guinea pig) allows to recapitulate shigellosis symptoms upon Shigella oral challenge. Historical reports suggest that dysentery and scurvy are both metabolic diseases associated with ascorbate-deficiency. Mammals which are susceptible to Shigella infection (humans, non-human primates and guinea pigs) are the lonely ones which are unable to synthesize ascorbate. We optimized a low-ascorbate diet to induce moderate ascorbate-deficiency but not scurvy in guinea pigs (Ascplasma conc.=1.6 μM vs 36 μM with optimal ascorbate supply). We demonstrated that moderate ascorbate-deficiency increases shigellosis severity during extended period of time (up to 48h) with all strains tested (Shigella flexneri 5a and 2a, Shigella sonnei). At late time-points, a massive influx of neutrophils was observed both within the disrupted colonic mucosa and in the luminal compartment, although Shigella remains able to disseminate deep into the organ to reach the sub-mucosal layer and the bloodstream. This new model of shigellosis opens new doors for the study both of Shigella infection strategy and innate and adaptive immune responses to Shigella infection. It may be also of a great interest to study the virulence of other pathogen for which no suitable animal model of infection is available (Vibrio cholerae, Yersinia pestis, Mycobacterium tuberculosis or Campylobacter jejuni, among others).SignificanceThe study of Shigella virulence cycle in vivo has been hampered by the lack of a suitable animal model, which would allow the colonic mucosa infection upon oral challenge. Based on historical reports and physiological aspects, it was suggested that ascorbate-deficiency may stand as a new dysentery risk-factor. To test this hypothesis, we set up a new ascorbate-deficient guinea pig model and demonstrated for the first time that the Shigella infectious process occurred for extended period of time (up to 48h) and demonstrated that shigellosis severity was higher in ascorbate-deficient animal. Ascorbate-deficient guinea pig model of infection may be used to assess the virulence of other pathogens for which no suitable animal model of infection is still lacking.


2017 ◽  
Vol 27 (6) ◽  
pp. 639-644 ◽  
Author(s):  
Maria Carmen Mora ◽  
Katharine R. Bittner ◽  
Kaitlyn E. Wong ◽  
Kevin P. Moriarty ◽  
David B. Tashjian ◽  
...  

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