Two-step curve fitting combined with a two-layered tissue model to quantify intrinsic fluorescence of cervical mucosal tissue in vivo

2021 ◽  
Author(s):  
Guo-Sheng Lin ◽  
Chong Ian Mok ◽  
Kung-Bin Sung
2015 ◽  
Vol 64 ◽  
pp. 246-260 ◽  
Author(s):  
Iván Gómez-Conde ◽  
Susana S. Caetano ◽  
Carlos E. Tadokoro ◽  
David N. Olivieri

2014 ◽  
Vol 83 (1) ◽  
pp. 28-38 ◽  
Author(s):  
Teresa M. DesRochers ◽  
Erica Palma Kimmerling ◽  
Dakshina M. Jandhyala ◽  
Wassim El-Jouni ◽  
Jing Zhou ◽  
...  

Shiga toxins (Stx) are a family of cytotoxic proteins that can cause hemolytic-uremic syndrome (HUS), a thrombotic microangiopathy, following infections by Shiga toxin-producingEscherichia coli(STEC). Renal failure is a key feature of HUS and a major cause of childhood renal failure worldwide. There are currently no specific therapies for STEC-associated HUS, and the mechanism of Stx-induced renal injury is not well understood primarily due to a lack of fully representative animal models and an inability to monitor disease progression on a molecular or cellular level in humans at early stages. Three-dimensional (3D) tissue models have been shown to be morein vivo-like in their phenotype and physiology than 2D cultures for numerous disease models, including cancer and polycystic kidney disease. It is unknown whether exposure of a 3D renal tissue model to Stx will yield a morein vivo-like response than 2D cell culture. In this study, we characterized Stx2-mediated cytotoxicity in a bioengineered 3D human renal tissue model previously shown to be a predictor of drug-induced nephrotoxicity and compared its response to Stx2 exposure in 2D cell culture. Our results demonstrate that although many mechanistic aspects of cytotoxicity were similar between 3D and 2D, treatment of the 3D tissues with Stx resulted in an elevated secretion of the kidney injury marker 1 (Kim-1) and the cytokine interleukin-8 compared to the 2D cell cultures. This study represents the first application of 3D tissues for the study of Stx-mediated kidney injury.


2018 ◽  
Vol 46 (6) ◽  
pp. 877-887 ◽  
Author(s):  
Hyung Joon Cho ◽  
Scott S. Verbridge ◽  
Rafael V. Davalos ◽  
Yong W. Lee

2011 ◽  
Vol 111 (6) ◽  
pp. 1703-1709 ◽  
Author(s):  
Megan M. Wenner ◽  
Thad E. Wilson ◽  
Scott L. Davis ◽  
Nina S. Stachenfeld

Although dose-response curves are commonly used to describe in vivo cutaneous α-adrenergic responses, modeling parameters and analyses methods are not consistent across studies. The goal of the present investigation was to compare three analysis methods for in vivo cutaneous vasoconstriction studies using one reference data set. Eight women (22 ± 1 yr, 24 ± 1 kg/m2) were instrumented with three cutaneous microdialysis probes for progressive norepinephrine (NE) infusions (1 × 10−8, 1 × 10−6, 1 × 10−5, 1 × 10−4, and 1 × 10−3 logM). NE was infused alone, co-infused with NG-monomethyl-l-arginine (l-NMMA, 10 mM) or Ketorolac tromethamine (KETO, 10 mM). For each probe, dose-response curves were generated using three commonly reported analyses methods: 1) nonlinear modeling without data manipulation, 2) nonlinear modeling with data normalization and constraints, and 3) percent change from baseline without modeling. Not all data conformed to sigmoidal dose-response curves using analysis 1, whereas all subjects' curves were modeled using analysis 2. When analyzing only curves that fit the sigmoidal model, NE + KETO induced a leftward shift in ED50 compared with NE alone with analyses 1 and 2 ( F test, P < 0.05) but only tended to shift the response leftward with analysis 3 (repeated-measures ANOVA, P = 0.08). Neither maximal vasoconstrictor capacity (Emax) in analysis 1 nor %change CVC change from baseline in analysis 3 were altered by blocking agents. In conclusion, although the overall detection of curve shifts and interpretation was similar between the two modeling methods of curve fitting, analysis 2 produced more sigmoidal curves.


2018 ◽  
Vol 6 ◽  
pp. 205031211876979 ◽  
Author(s):  
John M Baust ◽  
Anthony Robilotto ◽  
Peter Guerra ◽  
Kristi K Snyder ◽  
Robert G Van Buskirk ◽  
...  

Objectives: Cryoablation is an effective alternative treatment for cardiac arrhythmias offering shortened recovery and reduced side effects. As the use of cryoablation increases, the need for new devices and procedures has emerged. This has been driven by technological limitations including lengthy periods to generate a single lesion (3–5 min), uncertain transmurality, and differential efficacy. Furthermore, due to limited ablation capacity under high heat loads, cryo has had limited success in the treatment of ventricular arrhythmias. To this end, in this study we evaluated a new cryoablation catheter, ICEolate, for the targeted ablation of cardiac tissue. Methods: Performance assessment included calorimetry, freeze zone isothermal distribution characterization and catheter ablation capacity in a submerged, circulating, heat-loaded ex vivo tissue model. A pilot in vivo study was also conducted to assess ablative capacity of the cryocatheter in a fully beating heart. Results: Ex vivo studies demonstrated ice formation at the tip of a cryocatheter within 5 s and a tip temperature of ~−150°C within 10 s. The device repeatedly generated freeze zones of 2 cm × 3 cm in less than 2 min. Tissue model studies revealed the generation of a full thickness (5–10 mm) cryogenic lesion within 1 min with an opposite (transmural) surface temperature of <−60°C under a circulating 37°C heat load. Pilot in vivo studies demonstrated the delivery of an ablative “dose,” producing a continuous full thickness transmural linear lesion in <60 s at both atrial and ventricular sites. Conclusion: These studies suggest that the supercritical nitrogen cryodevice and ICEolate cryocatheter may provide for rapid, effective, controllable freezing of targeted tissue. The ablative power, speed, and directional freeze characteristics also offer the potential of improved safety via a reduction in procedural time compared to current cryoablation devices. These technological developments may open new avenues for the application of cryo to treat other cardiac arrhythmogenic disorders.


Author(s):  
J.B Weidhaas ◽  
J Holub ◽  
S Leibel ◽  
Z Fuks ◽  
D Eisenmann ◽  
...  

2018 ◽  
Vol 124 (3) ◽  
pp. 761-768 ◽  
Author(s):  
Ronald F. Coburn

Tissue PCOvalues have not been previously estimated under conditions where the blood carboxyhemoglobin % saturation ([COHb]) is at a normal level or increased. Tissue PCOvalues are not known for conditions when [COHb] is increased during CO therapy or during CO poisoning. Using a modified Krogh parallel capillary-tissue model, mean tissue PCOwas calculated for when [COHb] was 1, 5, 10, and 15% saturation, relevant to CO therapy, and 20, 30, and 40% saturation, relevant to CO poisoning. Calculations were made for the time during which CO was being inhaled, after cessation of CO uptake, and for different O2extractions from blood flowing in the model capillary. The T1/2of relevant CO reactions was used in these calculations. When the [COHb] increased to 5 to 10% saturation, mean tissue PCOvalues increased to 500 to 1,100% of values when the [COHb] was 1% saturation. When the [COHb] increased to 20 to 40% saturation, mean tissue PCOvalues increased to 2,300 to 5,700% of the 1% saturation value. Results indicate the utility of the modified Krogh model in furthering understanding the physiology of determinants of tissue PCOand should facilitate future studies of in vivo CO binding to different extravascular heme proteins during CO therapy and during CO poisoning.NEW & NOTEWORTHY Tissue PCOlevels resulting from carboxyhemoglobin concentrations achieved during CO therapy or during CO poisoning have not been previously estimated. Results published here show that at carboxyhemoglobin levels achieved during CO therapy there are 500 to 1,100% increases in mean tissue PCOvalues. With carboxyhemoglobin increases associated with toxic effects, there are 2,300 to 5,700% increases in the mean tissue PCO. These differences suggest a basis for understanding the therapeutic and toxic effects of CO.


2021 ◽  
Author(s):  
Junya Yoneda ◽  
Sachiko Nishikawa ◽  
Shigekazu Kurihara

Abstract Background Chemotherapy is frequently used in cancer treatment; however, it may cause adverse events, which must be managed. Reactive oxygen species (ROS) have been reported to be involved in the induction of intestinal mucositis and diarrhea, which are common side effects of treatment with fluoropyrimidine 5-fluorouracil (5-FU). Our previous studies have shown that oral administration of cystine and theanine (CT) increases glutathione (GSH) production in vivo. In the present study, we hypothesized that CT might inhibit oxidative stress, including the overproduction of ROS, and attenuate 5-FU-induced mucositis and diarrhea. Methods We investigated the inhibitory effect of CT administration on mucositis and diarrhea, as well as its mechanism, using a mouse model of 5-FU-induced intestinal mucositis. Results CT administration suppressed 5-FU-induced diarrhea and weight loss in the studied mice. After 5-FU administration, the GSH level and the GSH/GSSG ratio in the small intestine mucosal tissue decreased compared to normal control group; but CT administration improved the GSH/GSSG ratio to normal control levels. 5-FU induced ROS production in the basal region of the crypt of the small intestine mucosal tissue, which was inhibited by CT. CT did not affect the antitumor effect of 5-FU. Conclusions CT administration suppressed intestinal mucositis and diarrhea in a mouse model. This finding might be associated with the antioxidant characteristics of CT, including the improved rate of GSH redox and the reduced rate of ROS production in the small intestine mucosal tissue. CT might be a suitable candidate for the treatment of gastrointestinal mucositis associated with chemotherapy.


1981 ◽  
Vol 91 (1) ◽  
pp. 285-292 ◽  
Author(s):  
G. BOGÉ ◽  
A. RIGAL ◽  
G. PÉRES

The effects of 4 and 8 weeks fasting at 16 °C were studied in rainbow trout, Salmo gairdneri Richardson. After 4 and 8 weeks, the wet weights of the intestine of fasted animals are respectively 64% and 69% lower than those of fed animals. These effects especially concern the mucosal tissue. Glycine absorption (0.5 and 10 mm) was studied using an in vivo perfusion technique. After 4 weeks, the absolute amounts of 0.5 mm glycine absorbed by fasted and fed fish are similar. With 10 mm glycine, the absorption is slightly lower in fasted trout (−19%). After 8 weeks these differences are more marked, with glycine concentrations of 10 mm (−42%). Results expressed per 100 g body weight showed that these differences result partly from a weight gain of fed trout. Absorption expressed in terms of weight of dry intestine is higher in 4 and 8 weeks fasted animals, principally for the lower amino acid concentration (+61% and +111%). Larger differences were apparent when the absorptions were expressed in terms of dry weight of mucosal tissue (+122% and +225%).


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