scholarly journals Mutational spectrum of Mexican patients with tyrosinemia type 1: In silico modeling and predicted pathogenic effect of a novel missense FAH variant

2019 ◽  
Vol 7 (12) ◽  
Author(s):  
Isabel Ibarra‐González ◽  
Cynthia Fernández‐Lainez ◽  
Miguel Angel Alcántara‐Ortigoza ◽  
Ariadna González‐Del Angel ◽  
Liliana Fernández‐Henández ◽  
...  
Keyword(s):  
In Silico ◽  
Mutational Spectrum ◽  
Pathogenic Effect ◽  
In Silico Modeling ◽  
Tyrosinemia Type 1 ◽  
Mexican Patients

scholarly journals Structure and function insights garnered from in silico modeling of the thrombospondin type-1 domain-containing 7A antigen

2018 ◽  
Vol 87 (2) ◽  
pp. 136-145 ◽  
Author(s):  
Shana V. Stoddard ◽  
Colin L. Welsh ◽  
Maggie M. Palopoli ◽  
Serena D. Stoddard ◽  
Mounika P. Aramandla ◽  
...  
Keyword(s):  
In Silico ◽  
Structure And Function ◽  
In Silico Modeling ◽  
And Function

scholarly journals In Silico Modeling of Minimal Effective Insulin Doses Using the UVA/PADOVA Type 1 Diabetes Simulator

2017 ◽  
Vol 12 (2) ◽  
pp. 376-380 ◽  
Author(s):  
Enrique Campos-Náñez ◽  
Jennifer E. Layne ◽  
Howard C. Zisser
Keyword(s):  
Type 1 Diabetes ◽  
Blood Glucose ◽  
In Silico ◽  
Basal Insulin ◽  
Insulin Infusion ◽  
Glucose Levels ◽  
In Silico Modeling ◽  
Adolescents And Adults ◽  
Bolus Insulin

Background: The objective of this study was to identify the minimum basal insulin infusion rates and bolus insulin doses that would result in clinically relevant changes in blood glucose levels in the most insulin sensitive subjects with type 1 diabetes. Methods: The UVA/PADOVA Type 1 Diabetes Simulator in silico population of children, adolescents, and adults was administered a basal insulin infusion rate to maintain blood glucose concentrations at 120 mg/dL (6.7 mmol/L). Two scenarios were modeled independently after 1 hour of simulated time: (1) basal insulin infusion rates in increments of 0.01 U/h were administered and (2) bolus doses in increments of 0.01 U were injected. Subjects were observed for 4 hours to determine insulin delivery required to change blood glucose by 12.5 mg/dL (0.7 mmol/L) and 25 mg/dL (1.4 mmol/L) in only 5% of the in silico population. Results: The basal insulin infusion rates required to change blood glucose by 12.5 mg/dL and 25 mg/dL in 5% of children, adolescents, and adults were 0.03, 0.11, and 0.10 U/h and 0.06, 0.21, and 0.19 U/h, respectively. The bolus insulin doses required to change blood glucose by the target amounts in the respective populations were 0.10, 0.28, and 0.30 U and 0.19, 0.55, and 0.60 U. Conclusions: In silico modeling suggests that only a very small percentage of individuals with type 1 diabetes, corresponding to children with high insulin sensitivity and low body weight, will exhibit a clinically relevant change in blood glucose with very low basal insulin rate changes or bolus doses.

The PILGRIM Study: In Silico Modeling of a Predictive Low Glucose Management System and Feasibility in Youth with Type 1 Diabetes During Exercise

2014 ◽  
Vol 16 (6) ◽  
pp. 338-347 ◽  
Author(s):  
Thomas Danne ◽  
Christiana Tsioli ◽  
Olga Kordonouri ◽  
Sarah Blaesig ◽  
Kerstin Remus ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
In Silico ◽  
Management System ◽  
In Silico Modeling ◽  
Low Glucose ◽  
Glucose Management

Neuropharmacological Screening of Chiral and Non-chiral Phthalimide- Containing Compounds in Mice: in vivo and in silico Experiments

2019 ◽  
Vol 15 (1) ◽  
pp. 102-118 ◽  
Author(s):  
Carolina Campos-Rodríguez ◽  
José G. Trujillo-Ferrara ◽  
Ameyali Alvarez-Guerra ◽  
Irán M. Cumbres Vargas ◽  
Roberto I. Cuevas-Hernández ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
In Silico ◽  
Biological Properties ◽  
Chiral Molecules ◽  
Chiral Compounds ◽  
Plus Maze ◽  
In Silico Studies ◽  
The Central Nervous System

Background: Thalidomide, the first synthesized phthalimide, has demonstrated sedative- hypnotic and antiepileptic effects on the central nervous system. N-substituted phthalimides have an interesting chemical structure that confers important biological properties. Objective: Non-chiral (ortho and para bis-isoindoline-1,3-dione, phthaloylglycine) and chiral phthalimides (N-substituted with aspartate or glutamate) were synthesized and the sedative, anxiolytic and anticonvulsant effects were tested. Method: Homology modeling and molecular docking were employed to predict recognition of the analogues by hNMDA and mGlu receptors. The neuropharmacological activity was tested with the open field test and elevated plus maze (EPM). The compounds were tested in mouse models of acute convulsions induced either by pentylenetetrazol (PTZ; 90 mg/kg) or 4-aminopyridine (4-AP; 10 mg/kg). Results: The ortho and para non-chiral compounds at 562.3 and 316 mg/kg, respectively, decreased locomotor activity. Contrarily, the chiral compounds produced excitatory effects. Increased locomotor activity was found with S-TGLU and R-TGLU at 100, 316 and 562.3 mg/kg, and S-TASP at 316 and 562.3 mg/kg. These molecules showed no activity in the EPM test or PTZ model. In the 4-AP model, however, S-TGLU (237.1, 316 and 421.7 mg/kg) as well as S-TASP and R-TASP (316 mg/kg) lowered the convulsive and death rate. Conclusion: The chiral compounds exhibited a non-competitive NMDAR antagonist profile and the non-chiral molecules possessed selective sedative properties. The NMDAR exhibited stereoselectivity for S-TGLU while it is not a preference for the aspartic derivatives. The results appear to be supported by the in silico studies, which evidenced a high affinity of phthalimides for the hNMDAR and mGluR type 1.

scholarly journals Impact of Carbohydrate Counting Error on Glycemic Control in Open-Loop Management of Type 1 Diabetes: Quantitative Assessment Through an in silico Trial

2021 ◽  
pp. 193229682110123
Author(s):  
Chiara Roversi ◽  
Martina Vettoretti ◽  
Simone Del Favero ◽  
Andrea Facchinetti ◽  
Pratik Choudhary ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glycemic Control ◽  
In Silico ◽  
Open Loop ◽  
Random Errors ◽  
Linear Regression Models ◽  
Reference Case ◽  
Counting Error ◽  
The Impact

Background: In the management of type 1 diabetes (T1D), systematic and random errors in carb-counting can have an adverse effect on glycemic control. In this study, we performed an in silico trial aiming at quantifying the impact of different levels of carb-counting error on glycemic control. Methods: The T1D patient decision simulator was used to simulate 7-day glycemic profiles of 100 adults using open-loop therapy. The simulation was repeated for different values of systematic and random carb-counting errors, generated with Gaussian distribution varying the error mean from -10% to +10% and standard deviation (SD) from 0% to 50%. The effect of the error was evaluated by computing the difference of time inside (∆TIR), above (∆TAR) and below (∆TBR) the target glycemic range (70-180mg/dl) compared to the reference case, that is, absence of error. Finally, 3 linear regression models were developed to mathematically describe how error mean and SD variations result in ∆TIR, ∆TAR, and ∆TBR changes. Results: Random errors globally deteriorate the glycemic control; systematic underestimations lead to, on average, up to 5.2% more TAR than the reference case, while systematic overestimation results in up to 0.8% more TBR. The different time in range metrics were linearly related with error mean and SD ( R2>0.95), with slopes of [Formula: see text], [Formula: see text] for ∆TIR, [Formula: see text], [Formula: see text] for ∆TAR, and [Formula: see text], [Formula: see text] for ∆TBR. Conclusions: The quantification of carb-counting error impact performed in this work may be useful understanding causes of glycemic variability and the impact of possible therapy adjustments or behavior changes in different glucose metrics.

Liver Transplantation: A Safe and Definitive Alternative to Lifelong Nitisinone for Tyrosinemia Type 1

2021 ◽  
Author(s):  
Jagadeesh Menon ◽  
Naresh Shanmugam ◽  
Joseph J. Valamparampil ◽  
Abdul Hakeem ◽  
Mukul Vij ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Tyrosinemia Type 1
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