PP238 Budget Impact Of Methionine-Free Amino Acid Formula For Homocystinuria

2019 ◽  
Vol 35 (S1) ◽  
pp. 75-75
Author(s):  
Eduardo Mulinari ◽  
Nayara Castelano Brito ◽  
Lays Pires Marra

IntroductionThe National Committee for Health Technology Incorporation (CONITEC) evaluates health technologies to recommend their inclusion or exclusion within the Brazilian Public Health System (SUS), and uses the budget impact assessment to estimate costs to the system. This study estimated the budget impact of the supply of methionine-free amino acid formula (MFAAf) for patients with classical homocystinuria (HCU) in the SUS.MethodsThe incidence of one case per 250,000 live births in Brazil and the registration of a Brazilian association of patients with HCU was assumed to calculate the population. Mortality and responsiveness to pyridoxine rates were applied. The costs of treatment were estimated according to the recommended dosage in literature and public purchasing prices. For calculating the dose of MFAAf patients, a median age of 19 years and weight of 60 kg were assumed, according to Brazilian study data.ResultsThe annual cost of treatment was estimated at BRL 77,000 (USD 21,084) per patient. The incorporation of MFAAf for HCU would generate a budget impact in SUS of around BRL 37 million (USD 10.1 million) in 2019 and BRL 188 million (USD 51.5 million) after five years which considers the epidemiological data, and a budget impact of around BRL 6.4 million (USD 1.75 million) in 2019 and BRL 33 million (USD 9 million) after five years which considers the information of a Brazilian association of patients with HCU. The wide range of values in the incremental budgetary impact is due to the lack of information on the epidemiology of the disease in Brazil.ConclusionsThe incorporation of the MFAAf in the SUS represents an important budgetary impact and covers a small number of patients. CONITEC recommended the incorporation of the MFAAf in the SUS, according to clinical protocol.

2004 ◽  
Vol 129 (5) ◽  
pp. 653-659 ◽  
Author(s):  
Guohai Xia ◽  
Lailiang Cheng

One-year-old `Concord' grapevines (Vitis labruscana Bailey) were fertigated with 0, 5, 10, 15, or 20 mm N in a modified Hoagland's solution for 8 weeks during summer. Half of the vines fertigated at each N concentration were sprayed with 3% foliar urea twice in late September while the rest served as controls. Four vines from each treatment combination were destructively sampled during dormancy to determine the levels and forms of N and carbohydrates. Nitrogen fertigation during the summer did not significantly alter vine N concentration whereas foliar urea application in the fall significantly increased vine N concentration. In response to foliar urea application, concentrations of both free amino acid-N and protein-N increased, but the ratio of protein-N to free amino acid-N decreased. Arginine was the most abundant amino acid in free amino acids and proteins, and its concentration was linearly correlated with vine N concentration. Concentrations of total nonstructural carbohydrates (TNC) decreased slightly in response to N supply from fertigation. Foliar urea application in the fall significantly decreased TNC concentration at each N fertigation level. Starch, glucose, and fructose decreased in response to foliar urea applications, but sucrose concentration remained unaffected. Approximately 60% of the carbon decrease in TNC caused by foliar urea application was recovered in proteins and free amino acids. We conclude that free amino acids account for a larger proportion of the N in vines sprayed with foliar urea compared with the unsprayed vines, but proteins remain as the main form of N storage. In response to foliar urea application, part of the carbon from TNC is incorporated into proteins and free amino acids, leading to a decrease in the carbon stored in TNC and an increase in the carbon stored in proteins and free amino acids.


1987 ◽  
Vol 11 (6) ◽  
pp. 533-539 ◽  
Author(s):  
Patricia A. Heller ◽  
Eva Shronts ◽  
Salim Akrabawi ◽  
Steven B. Heymsfield

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 616
Author(s):  
Lionel Tarrago ◽  
Sandrine Grosse ◽  
David Lemaire ◽  
Laetitia Faure ◽  
Mathilde Tribout ◽  
...  

In proteins, methionine (Met) can be oxidized into Met sulfoxide (MetO). The ubiquitous methionine sulfoxide reductases (Msr) A and B are thiol-oxidoreductases reducing MetO. Reversible Met oxidation has a wide range of consequences, from protection against oxidative stress to fine-tuned regulation of protein functions. Bacteria distinguish themselves by the production of molybdenum-containing enzymes reducing MetO, such as the periplasmic MsrP which protects proteins during acute oxidative stress. The versatile dimethyl sulfoxide (DMSO) reductases were shown to reduce the free amino acid MetO, but their ability to reduce MetO within proteins was never evaluated. Here, using model oxidized proteins and peptides, enzymatic and mass spectrometry approaches, we showed that the Rhodobacter sphaeroides periplasmic DorA-type DMSO reductase reduces protein bound MetO as efficiently as the free amino acid L-MetO and with catalytic values in the range of those described for the canonical Msrs. The identification of this fourth type of enzyme able to reduce MetO in proteins, conserved across proteobacteria and actinobacteria, suggests that organisms employ enzymatic systems yet undiscovered to regulate protein oxidation states.


2019 ◽  
Vol 35 (S1) ◽  
pp. 40-40
Author(s):  
Eduardo Mulinari ◽  
Nayara Castelano Brito ◽  
Lays Pires Marra

IntroductionThe National Committee for Health Technology Incorporation (CONITEC) evaluates health technologies to recommend their inclusion or exclusion within the Brazilian Public Health System (SUS), and uses the budget impact assessment to estimate costs to the system. The Ministry of Health (MS) guideline recommends treatment of phenylketonuria (PKU) with restricted phenylalanine diet and phenylalanine-free amino acid formula (PFAAf) supplementation. CONITEC evaluated the inclusion of sapropterin dihydrochloride for PKU in the SUS.MethodsThe population eligible for treatment was evaluated by the number of patients receiving PFAAf between 2014 and 2017 registered in the SUS. Patients were stratified by age/weight and a simple linear regression was performed to estimate the future population. The costs of treatment and testing the responsiveness of sapropterin dihydrochloride were estimated according to the recommended dosage guideline of the MS, leaflet and public purchasing prices. A univariate deterministic sensitivity analysis was performed to evaluate different prices, responsiveness test methods and variations in the reduction of formula use.ResultsThe incorporation of sapropterin dihydrochloride would generate an incremental budget impact in the SUS of around BRL 79 million (USD 21.7 million) in 2019 and BRL 300 million (USD 82.1 million) in five years (2019-2023). The univariate sensitivity analysis estimated that the incremental budget impact could be between BRL 66 and BRL 103 million (USD 18 and USD 28 million) in the first year and between BRL 251 and BRL 388 million (USD 69 and USD 106 million) in five years. Sensitivity analysis showed that the price of sapropterin dihydrochloride was the most sensitive variable in the model.ConclusionsThe incorporation of sapropterin dihydrochloride in the SUS represents a significant budgetary impact and covers a small number of patients. Sapropterin dihydrochloride was recommended by CONITEC for the treatment of women with PKU, with a positive drug responsiveness test, and who are in the preconception period or in the gestational period.


Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
EJ Cho ◽  
XL Piao ◽  
MH Jang ◽  
SY Park ◽  
SW Kwon ◽  
...  

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
BM Silva ◽  
AP Oliveira ◽  
DM Pereira ◽  
C Sousa ◽  
RM Seabra ◽  
...  

Author(s):  
Omer Tammo ◽  
Hacer Uyanikoglu ◽  
İsmail Koyuncu

Aim and Objective: This study aimed to explore the plasma free amino acid (FAA) and carnitine levels in pregnant women with cesarean scar pregnancy (CSP), and to compare them with those of healthy pregnant women. Materials and Methods: This prospective and randomized controlled study was conducted in patients admitted to Harran University Medical Faculty Hospital Obstetrics Clinic between January 2018 and January 2019. A total of 60 patients were included in the study, and the patients were divided into two groups: CSP group (n = 30) and healthy pregnant group as the control group (n = 30). The blood samples were taken from the participants between 7 - 12 weeks of gestation. Twentyseven carnitines and their esters and 14 FAAs were analysed by liquid chromatography – mass spectrometry (LC-MS/MS). Results: The mean plasma concentrations of some carnitines, including C2, C5, C5-OH, C5-DC, C6, C8-1, C12, C14, C14- 1, C14-2, C16, C16-1, C18, and C18-1 were significantly higher in CSP group than in the control group. However, other carnitines, including C0, C3, C4, C4-DC, C5-1, C6-DC, C8, C8-DC, C10, C10-1, C18-1-OH, and C18-2 were similar in both groups. The plasma levels of some FAAs, including Methyl Glutaryl, Leu, Met, Phe, Arg, Orn, and Glu values were significantly higher in CSP group than in the control group. However, there was no statistically significance in other FAA levels, including Val, Asa, Tyr, Asp, Ala, Cit, and Gly between the two groups. Additionally, Pearson’s correlation analysis showed that there were significantly positive correlations between many FAA and carnitine values. Conclusion: Since several plasma carnitine and FAA levels were higher in CSP group than in the control group, we think that scar pregnancy increases metabolic need for myometrial invasion. Also, we think that these results may be useful in clinical practice for CSP diagnosis.


2020 ◽  
Vol 22 (9) ◽  
pp. 657-662 ◽  
Author(s):  
Mustafa Celik ◽  
Alper Şen ◽  
İsmail Koyuncu ◽  
Ataman Gönel

Aim and Objective:: To determine the mechanisms present in the etiopathogenesis of nasal polyposis. It is not clear whether amino acids contribute in a causal way to the development of the disease. Therefore, the aim of this study was to determine the plasma-free amino acid profile in patients with nasal polyposis and to compare the results with a healthy control group. Materials and Methods:: This was a prospective controlled study that took place in the Otolaryngology Department at the Harran University Faculty of Medicine between April 2017 and April 2018. Plasmafree amino acid profile levels were studied in serum samples taken from a patient group and a healthy control group. Patients who were diagnosed with bilateral diffuse nasal polyposis and were scheduled for surgical interventions were included in this study. Individuals whose age, gender, and body mass index values were compatible with that of the patient group and who did not have any health problems were included in the control group. All the participants whose levels of plasma-free amino acid were thought to be affected by one or more of the following factors were excluded from the study: smoking and alcohol use, allergic rhinitis presence, the presence of acute or chronic sinusitis, a history of endoscopic sinus surgery, unilateral nasal masses, a history of chronic drug use, systemic or topical steroid use in the last three months for any reason, and liver, kidney, hematological, cardiovascular, metabolic, neurological, or psychiatric disorders or malignancies. Results: In patients with nasal polyposis, 3-methyl histidine (3-MHIS: nasal polyposis group (ng) = 3.22 (1.92 – 6.07); control group (cg) = 1.21 (0.77 – 1.68); p = 0.001); arginine (arg: ng = 98.95 (70.81 – 117.75); cg = 75.10 (54.49 – 79.88); p = 0.005); asparagine (asn: ng = 79.84 (57.50 – 101.44); cg = 60.66 (46.39 – 74.62); p = 0.021); citrulline (cit: ng = 51.83 (43.81 – 59.78); cg = 38.33 (27.81 – 53.73); p = 0.038); cystine (cys: ng = 4.29 (2.43 – 6.66); cg = 2.41 (1.51 – 4.16); p = 0.019); glutamic acid (glu: ng = 234.86 (128.75 – 286.66); cg = 152.37 (122.51 – 188.34); p = 0.045); histidine (his: ng = 94.19 (79.34 – 113.99); cg = 74.80 (62.76 – 98.91); p = 0.018); lysine (lys: ng = 297.22 (206.55 – 371.25); cg = 179.50 (151.58 – 238.02); p = 0.001); ornithine (ng = 160.62 (128.36 – 189.32); cg = 115.91 (97.03 – 159.91); p = 0.019); serine (ser: ng = 195.15 (151.58 – 253.07); cg = 83.07 (67.44 – 92.44); p = 0.001); taurine (tau: ng = 74.69 (47.00 – 112.13); cg = 53.14 (33.57 – 67.31); p = 0.006); tryptophan (trp: ng = 52.31 (33.81 – 80.11); cg = 34.44 (25.94 – 43.07); p = 0.005), homocitrulline (ng = 1.75 (1.27 – 2.59); cg = 0.00 (0.00 – 0.53); p = 0.001); norvaline (ng = 6.90 (5.61 – 9.18); cg = 4.93 (3.74 – 7.13); p = 0.021); argininosuccinic acid (ng = 14.33 (10.06 – 25.65); cg = 12.22 (5.77 – 16.87) p = 0.046); and plasma concentrations were significantly higher than in the healthy control group (p <0.05). However, the gamma-aminobutyric acid (gaba: ng = 0.16 (0.10 – 0.24); cg = 0.21 (0.19 – 0.29); p = 0.010) plasma concentration was significantly lower in the nasal polyposis group than in the healthy control group. Conclusion: In this study, plasma levels of 15 free amino acids were significantly higher in the nasal polyposis group than in the healthy control group. A plasma level of 1 free amino acid was found to be significantly lower in the nasal polyposis group compared to the healthy control group. Therefore, it is important to determine the possibility of using the information obtained to prevent the recurrence of the condition and to develop effective treatment strategies. This study may be a milestone for studies of this subject. However, this study needs to be confirmed by further studies conducted in a larger series.


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