scholarly journals Dietary Mannose Supplementation in Phosphomannomutase 2 Deficiency (PMM2-CDG)

2020 ◽  
Author(s):  
Roman Taday ◽  
Marianne Grüneberg ◽  
Ingrid DuChesne ◽  
Janine Reunert ◽  
Thorsten Marquardt
Keyword(s):  
Biological Effects ◽  
Protein Glycosylation ◽  
Therapeutic Approaches ◽  
Short Term ◽  
Everyday Clinical Practice ◽  
Time Period ◽  
Mannose Metabolism ◽  
Mean Time

Abstract BackgroundPMM2-CDG (CDG-Ia) is the most frequent N-glycosylation disorder. While supplying mannose to PMM2-deficient fibroblasts corrects the altered N-glycosylation in vitro, short term therapeutic approaches with mannose supplementation in PMM2-CDG patients have been unsuccessful. Mannose found no further mention in the design of a potential therapy for PMM2-CDG in the past years, as it applies as ineffective. This retrospective study analyzes the first long term mannose supplementation in 20 PMM2-CDG patients. Mannose was given at a total of 1–2 g mannose/kg b.w./d divided into 5 single doses over a mean time of 60,7 months. Protein glycosylation, blood mannose concentration and clinical presentation were monitored in everyday clinical practice.ResultsAfter a mean time period of more than 1 year the majority of patients showed significant improvements in protein glycosylation.ConclusionLong-term dietary D-mannose supplementation shows biological effects in PMM2-CDG, an inherited disorder of mannose metabolism. It improves glycosylation in the majority of patients and could become the first cornerstone in the treatment of this disease.

scholarly journals Dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG)

2020 ◽  
Author(s):  
Roman Taday ◽  
Marianne Grüneberg ◽  
Ingrid DuChesne ◽  
Janine Reunert ◽  
Thorsten Marquardt
Keyword(s):  
Biological Effects ◽  
Protein Glycosylation ◽  
Therapeutic Approaches ◽  
Short Term ◽  
Everyday Clinical Practice ◽  
Time Period ◽  
Mannose Metabolism ◽  
Mean Time

Abstract Background PMM2-CDG (CDG-Ia) is the most frequent N-glycosylation disorder. While supplying mannose to PMM2-deficient fibroblasts corrects the altered N-glycosylation in vitro, short term therapeutic approaches with mannose supplementation in PMM2-CDG patients have been unsuccessful. Mannose found no further mention in the design of a potential therapy for PMM2-CDG in the past years, as it applies as ineffective. This retrospective study analyzes the first long term mannose supplementation in 20 PMM2-CDG patients. Mannose was given at a total of 1-2 g mannose/kg b.w./d divided into 5 single doses over a mean time of 60,7 months. Protein glycosylation, blood mannose concentration and clinical presentation were monitored in everyday clinical practice. Results After a mean time period of more than 1 year the majority of patients showed significant improvements in protein glycosylation. Conclusion Long-term dietary D-mannose supplementation shows biological effects in PMM2-CDG, an inherited disorder of mannose metabolism. It improves glycosylation in the majority of patients and could become the first cornerstone in the treatment of this disease.

scholarly journals Dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG)

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Roman Taday ◽  
Marianne Grüneberg ◽  
Ingrid DuChesne ◽  
Janine Reunert ◽  
Thorsten Marquardt
Keyword(s):  
Biological Effects ◽  
Randomized Study ◽  
Protein Glycosylation ◽  
Therapeutic Approaches ◽  
Double Blind ◽  
Time Period ◽  
Mean Time

Abstract Background PMM2-CDG (CDG-Ia) is the most frequent N-glycosylation disorder. While supplying mannose to PMM2-deficient fibroblasts corrects the altered N-glycosylation in vitro, short term therapeutic approaches with mannose supplementation in PMM2-CDG patients have been unsuccessful. Mannose found no further mention in the design of a potential therapy for PMM2-CDG in the past years, as it applies to be ineffective. This retrospective study analyzes the first long term mannose supplementation in 20 PMM2-CDG patients. Mannose was given at a total of 1–2 g mannose/kg b.w./d divided into 5 single doses over a mean time of 57,75 ± 25,85 months. Protein glycosylation, blood mannose concentration and clinical presentation were monitored in everyday clinical practice. Results After a mean time period of more than 1 year the majority of patients showed significant improvements in protein glycosylation. Conclusion Dietary mannose supplementation shows biological effects in PMM2-CDG patients improving glycosylation in the majority of patients. A double-blind randomized study is needed to examine the role of mannose in the design of a therapy for children with PMM2-CDG in more detail.

scholarly journals Effect of polyphenols on the intestinal and placental transport of some bioactive compounds

2010 ◽  
Vol 23 (1) ◽  
pp. 47-64 ◽  
Author(s):  
Fátima Martel ◽  
Rosário Monteiro ◽  
Conceição Calhau
Keyword(s):  
Bioactive Compounds ◽  
Biological Effects ◽  
Alcoholic Beverages ◽  
Short Term ◽  
Intestinal Epithelia ◽  
The Past ◽  
Cell Culture Systems ◽  
Epithelial Barriers

Polyphenols are a group of widely distributed phytochemicals present in most foods of vegetable origin. A growing number of biological effects have been attributed to these molecules in the past few years and only recently has their interference with the transport capacity of epithelial barriers received attention. This review will present data obtained concerning the effect of polyphenols upon the transport of some compounds (organic cations, glucose and the vitamins thiamin and folic acid) at the intestinal and placental barriers. Important conclusions can be drawn: (i) different classes of polyphenols affect transport of these bioactive compounds at the intestinal epithelia and the placenta; (ii) different compounds belonging to the same phenolic family often possess opposite effects upon transport of a given molecule; (iii) the acute and chronic/short-term and long-term exposures to polyphenols do not produce parallel results and, therefore, care should be taken when extrapolating results; (iv) the effect of polyphenolics in combination may be very different from the expected ones taking into account the effect of each of these compounds alone, and so care should be taken when speculating on the effect of a drink based on the effect of one component only; (v) care should be taken in drawing conclusions for alcoholic beverages from results obtained with ethanol alone. Although most of the data reviewed in the present paper refer to in vitro experiments with cell-culture systems, these studies raise a concern about possible changes in the bioavailability of substrates upon concomitant ingestion of polyphenols.

Ultrastructural investigations of MDL 19,660-induced effects on the canine platelet and megakaryocyte

1990 ◽  
Vol 48 (3) ◽  
pp. 374-375
Author(s):  
D.E. Loudy ◽  
J. Sprinkle-Cavallo ◽  
J.T. Yarrington ◽  
F.Y. Thompson ◽  
J.P. Gibson
Keyword(s):  
Antidepressant Drug ◽  
Beagle Dogs ◽  
Long Term Effects ◽  
Short Term ◽  
Platelet Counts ◽  
Toxicological Studies ◽  
Induced Aggregation ◽  
Internal Architecture

Previous short term toxicological studies of one to two weeks duration have demonstrated that MDL 19,660 (5-(4-chlorophenyl)-2,4-dihydro-2,4-dimethyl-3Hl, 2,4-triazole-3-thione), an antidepressant drug, causes a dose-related thrombocytopenia in dogs. Platelet counts started to decline after two days of dosing with 30 mg/kg/day and continued to decrease to their lowest levels by 5-7 days. The loss in platelets was primarily of the small discoid subpopulation. In vitro studies have also indicated that MDL 19,660: does not spontaneously aggregate canine platelets and has moderate antiaggregating properties by inhibiting ADP-induced aggregation. The objectives of the present investigation of MDL 19,660 were to evaluate ultrastructurally long term effects on platelet internal architecture and changes in subpopulations of platelets and megakaryocytes.Nine male and nine female beagle dogs were divided equally into three groups and were administered orally 0, 15, or 30 mg/kg/day of MDL 19,660 for three months. Compared to a control platelet range of 353,000- 452,000/μl, a doserelated thrombocytopenia reached a maximum severity of an average of 135,000/μl for the 15 mg/kg/day dogs after two weeks and 81,000/μl for the 30 mg/kg/day dogs after one week.

ON THE CONSUMPTION/DISTRIBUTION THEOREM UNDER THE LONG-RUN GROWTH CRITERION SUBJECT TO A DRAWDOWN CONSTRAINT

2010 ◽  
Vol 13 (06) ◽  
pp. 931-957 ◽  
Author(s):  
MICHAEL J. KLASS ◽  
KRZYSZTOF NOWICKI
Keyword(s):  
Growth Rate ◽  
Short Term ◽  
Long Run ◽  
Time Period ◽  
Total Capital ◽  
Growth Criterion ◽  
Drawdown Constraint ◽  
Riskless Asset ◽  
Distribution Theorem

Consider any discrete time sequence of investment fortunes Fn which has a finite long-run growth rate [Formula: see text] when subject to the present value capital drawdown constraint Fne-rn ≥ λ* max 0≤k≤nFke-rk, where 0 ≤ λ* < 1, in the presence of a riskless asset affording a return of er dollars per time period per dollar invested. We show that money can be withdrawn for consumption from the invested capital without either reducing the long-run growth rate of such capital or violating the drawdown constraint for our capital sequence, while simultaneously increasing the amount of capital withdrawn for consumption at the identical long-term rate of V(r, λ*). We extend this result to an exponentially increasing number of consumption categories and discuss how additional yearly contributions can temporarily augment the total capital under management. In addition, we assess the short-term practicality of creating such an endowment/consumption/distribution program.

Long-term Safety and Efficacy of Mexiletine in Myotonic Dystrophy Types 1 and 2

2021 ◽  
pp. 10.1212/CPJ.0000000000001073
Author(s):  
Christina Mousele ◽  
Emma Matthews ◽  
Robert Pitceathly ◽  
Michael Hanna ◽  
Susan McDonald ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Sodium Channels ◽  
Genetic Disorders ◽  
Clinical Feature ◽  
Efficacy And Safety ◽  
Voltage Gated Sodium Channels ◽  
Time Period ◽  
Mean Time

AbstractBackground:Myotonic dystrophy types 1 and 2 are progressive multisystem genetic disorders, whose core clinical feature is myotonia. Mexiletine, an antagonist of voltage-gated sodium channels, is a recommended anti-myotonic agent in the non-dystrophic myotonias, but its use in myotonic dystrophy is limited due to lack of data regarding its long-term efficacy and safety profile.Methods:To address this issue, this study retrospectively evaluated patients with myotonic dystrophy receiving mexiletine over a mean time-period of 32.9 months (range 0.1 to 216 months).Results:This study demonstrated that 96% of patients reported some improvement in myotonia symptoms with mexiletine treatment. No clinically relevant cardiac adverse events were associated with the long-term use of mexiletine.Conclusions:These findings support that mexiletine is both safe and effective when used long-term in myotonic dystrophy.Classification of Evidence:This study provides class IV evidence that mexiletine is a well-tolerated and effective treatment for myotonic dystrophy types 1 and 2.

The effect of the financing structure on the return on the market share in Saudi companies An Empirical Study: أثر هيكل التمويل على عائد السهم السوقي في الشركات السعودية: دراسة تطبيقية

2020 ◽  
Vol 4 (11) ◽  
Author(s):  
Fatimah Mohammad Asiri
Keyword(s):  
Market Share ◽  
Food Production ◽  
Analytical Approach ◽  
Negative Impact ◽  
Short Term ◽  
Financing Structure ◽  
Time Period ◽  
Comprehensive Survey ◽  
Study Population

The study aimed to identify the influence of the financing structure on the return of the market share in Saudi corporations/companies. The study applied the descriptive-analytical approach, and the study population consisted of some joint-stock companies in the Saudi stock market, where the study sample consisted of (75) companies in five productive sectors where concentration was made on the following sectors: (basic materials, long-term commodities, energy, food production, capital goods). Method of the comprehensive survey was used for all companies. The data was analyzed using the Panel Data method through the STATA program. The study concluded several findings, the most important of which are that short-term debt (liabilities) have a negative impact on the return on the market share, as increasing short debts (liabilities) lead to a decrease in the return on the market share, and that long-term debt (liabilities) have no effect on the return on the market share, and equity has a negative impact on the return on the market share, as the increase in financing through equity leads to a decrease in the return on the market share. The study recommended the necessity of diversification between sources of financing and not limited to debt and long & short-term liabilities only. It also recommended conducting such a study on other sectors or conducting it on the whole market which may result in improving results, and also recommends expanding the time period more than five years, which may lead to improve results.

Short-term effect of aldosterone on NEM-sensitive ATPase in rat collecting tubule

1989 ◽  
Vol 257 (2) ◽  
pp. F177-F181 ◽  
Author(s):  
C. Khadouri ◽  
S. Marsy ◽  
C. Barlet-Bas ◽  
A. Doucet
Keyword(s):  
Atpase Activity ◽  
Affinity Constant ◽  
Short Term ◽  
Collecting Tubule ◽  
Lag Period ◽  
In Vitro Effects ◽  
Collecting Tubules

Because previous studies indicated that in the collecting tubule, N-ethylmaleimide (NEM)-sensitive ATPase, the biochemical equivalent of the proton pump, is controlled by mineralocorticoids in the long term, the present study was designed to investigate whether such control also exists in the short term. Therefore we investigated the in vivo and in vitro effects of aldosterone on the enzyme activity in cortical and outer medullary collecting tubules (CCT and MCT, respectively) from adrenalectomized rats. Administration of aldosterone (10 micrograms/kg body wt) markedly stimulated NEM-sensitive ATPase activity in the CCT and MCT within 3 h. Similarly, incubating CCT or MCT for 3 h in the presence of 10(-8) M aldosterone enhanced NEM-sensitive ATPase activity up to values similar to those previously measured in the corresponding nephron segments of normal rats. In vitro stimulation of NEM-sensitive ATPase was dose dependent in regard to aldosterone (apparent affinity constant approximately 10(-9) M), appeared after a 30-min lag period, and reached its maximum after 2-2.5 h. Finally, actinomycin D and cycloheximide totally abolished the in vitro action of aldosterone, demonstrating the involvement of protein synthesis in this process.

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