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Molecular Genetics & Genomic Medicine Oct 2022Typical patients with KCNQ2 (OMIM# 602235) epileptic encephalopathy present early neonatal-onset intractable seizures with a burst suppression EEG pattern and severe... (Review)
Review
BACKGROUND
Typical patients with KCNQ2 (OMIM# 602235) epileptic encephalopathy present early neonatal-onset intractable seizures with a burst suppression EEG pattern and severe developmental delay or regression, and those patients always fail first-line treatment with sodium channel blockers. Vitamin B6, either pyridoxine or pyridoxal 50-phosphate, has been demonstrated to improve seizure control in intractable epilepsy.
METHODS
Here, we collected and summarized the clinical data for four independent cases diagnosed with pyridoxine-responsive epileptic encephalopathy, and their exome sequencing data. Moreover, we reviewed all published cases and summarized the clinical features, genetic variants, and treatment of pyridoxine-responsive KCNQ2 epileptic encephalopathy.
RESULTS
All four cases showed refractory seizures during the neonatal period or infancy, accompanied by global development delay. Four pathogenetic variants of KCNQ2 were uncovered and confirmed by Sanger sequencing: KCNQ2 [NM_172107.4: c.2312C > T (p.Thr771Ile), c.873G > C (p.Arg291Ser), c.652 T > A (p.Trp218Arg) and c.913-915del (p. Phe305del)]. Sodium channel blockers and other anti-seizure medications failed to control their seizures. The frequency of seizures gradually decreased after treatment with high-dose pyridoxine. In case 1, case 2, and case 4, clinical seizures relapsed when pyridoxine was withdrawn, and seizures were controlled again when pyridoxine treatment was resumed.
CONCLUSION
Our study suggests that pyridoxine may be a promising adjunctive treatment option for patients with KCNQ2 epileptic encephalopathy.
Topics: Electroencephalography; Epilepsy, Generalized; Humans; Infant, Newborn; KCNQ2 Potassium Channel; Phosphates; Pyridoxal; Pyridoxine; Sodium Channel Blockers
PubMed: 35906921
DOI: 10.1002/mgg3.2024 -
International Journal of Molecular... Mar 2024Enzymes reliant on pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B, hold significant importance in both biology and medicine. They facilitate... (Review)
Review
Enzymes reliant on pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B, hold significant importance in both biology and medicine. They facilitate various biochemical reactions, particularly in amino acid and neurotransmitter metabolisms. Vitamin B is absorbed by organisms in its non-phosphorylated form and phosphorylated within cells via pyridoxal kinase (PLK) and pyridox-(am)-ine 5'-phosphate oxidase (PNPOx). The flavin mononucleotide-dependent PNPOx enzyme converts pyridoxine 5'-phosphate and pyridoxamine 5'-phosphate into PLP. PNPOx is vital for both biosynthesis and salvage pathways in organisms producing B vitamers. However, for those depending on vitamin B as a nutrient, PNPOx participates only in the salvage pathway. Transferring the PLP produced via PNPOx to client apo-enzymes is indispensable for their catalytic function, proper folding and targeting of specific organelles. PNPOx activity deficiencies due to inborn errors lead to severe neurological pathologies, particularly neonatal epileptic encephalopathy. PNPOx maintains PLP homeostasis through highly regulated mechanisms, including structural alterations throughout the catalytic cycle and allosteric PLP binding, influencing substrate transformation at the active site. Elucidation at the molecular level of the mechanisms underlying PNPOx activity deficiencies is a requirement to develop personalized approaches to treat related disorders. Finally, despite shared features, the few PNPOx enzymes molecularly and functionally studied show species-specific regulatory properties that open the possibility of targeting it in pathogenic organisms.
Topics: Humans; Infant, Newborn; Oxidoreductases; Phosphates; Pyridoxaminephosphate Oxidase; Pyridoxal Phosphate; Vitamin B 6; Pyridoxine; Metabolic Diseases; Vitamins
PubMed: 38542149
DOI: 10.3390/ijms25063174 -
Journal of Fluorescence Mar 2023Anions and cations have a key role in our normal life. Cu ion is a crucial trace element accountable for the part of several cellular enzymes and proteins, including... (Review)
Review
Anions and cations have a key role in our normal life. Cu ion is a crucial trace element accountable for the part of several cellular enzymes and proteins, including cytochrome c oxidase, dopamine monooxygenase, Cu/Zn superoxide dismutase, and ceruloplasmin. WHO has found the extreme acceptable level of Cu ions in drinking water is up to 2.0 ppm. Excess use of Cu ions is associated with various human genetic disorders. Thus, the visualization of Cu ions to avoid its toxic effects in chemical and biological systems is significant. In this review we have summarized sensors based on catalytic hydrolysis of picolinate to detect Cu ions. The sensors based on hydrolysis of picolinate are very selective as compared to the other sensors for Cu ions detection. We have focused on describing the structure, spectral properties, detection limits, and bioimaging model of the sensors.
Topics: Humans; Copper; Hydrolysis; Cations; Fluorescent Dyes
PubMed: 36480123
DOI: 10.1007/s10895-022-03078-y -
Canadian Journal of Gastroenterology &... Nov 2014Constipation is an uncomfortable and common condition that affects many, irrespective of age. Since 1500 BC and before, health care practitioners have provided... (Review)
Review
BACKGROUND
Constipation is an uncomfortable and common condition that affects many, irrespective of age. Since 1500 BC and before, health care practitioners have provided treatments and prevention strategies to patients for chronic constipation despite the significant variation in both medical and personal perceptions of the condition.
OBJECTIVE
To review relevant research evidence from clinical studies investigating the efficacy and safety of commercially available pharmacological laxatives in Canada, with emphasis on studies adopting the Rome criteria for defining functional constipation.
SEARCH METHODS
PubMed, Medline, Embase and Evidence-Based Medicine Reviews databases were searched for blinded or randomized clinical trials and meta-analyses assessing the efficacy of nonstimulant and stimulant laxatives for the treatment of functional constipation.
RESULTS
A total of 19 clinical studies and four meta-analyses were retrieved and abstracted regarding study design, participants, interventions and outcomes. The majority of studies focused on polyethylene glycol compared with placebo. Both nonstimulant and stimulant laxatives provided better relief of constipation symptoms than placebo according to both objective and subjective measures. Only one study compared the efficacy of a nonstimulant versus a stimulant laxative, while only two reported changes in quality of life. All studies reported minor side effects due to laxative use, regardless of treatment duration, which ranged from one week to one year. Laxatives were well tolerated by both adults and children.
Topics: Bisacodyl; Canada; Citrates; Constipation; Dioctyl Sulfosuccinic Acid; Humans; Lactulose; Laxatives; Magnesium Oxide; Organometallic Compounds; Paraffin; Picolines; Polyethylene Glycols; Psyllium; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25390617
DOI: 10.1155/2014/631740 -
Open Biology Mar 2020A perturbed uptake of micronutrients, such as minerals and vitamins, impacts on different human diseases, including cancer and neurological disorders. Several data... (Review)
Review
A perturbed uptake of micronutrients, such as minerals and vitamins, impacts on different human diseases, including cancer and neurological disorders. Several data converge towards a crucial role played by many micronutrients in genome integrity maintenance and in the establishment of a correct DNA methylation pattern. Failure in the proper accomplishment of these processes accelerates senescence and increases the risk of developing cancer, by promoting the formation of chromosome aberrations and deregulating the expression of oncogenes. Here, the main recent evidence regarding the impact of some B vitamins on DNA damage and cancer is summarized, providing an integrated and updated analysis, mainly centred on vitamin B. In many cases, it is difficult to finely predict the optimal vitamin rate that is able to protect against DNA damage, as this can be influenced by a given individual's genotype. For this purpose, a precious resort is represented by model organisms which allow limitations imposed by more complex systems to be overcome. In this review, we show that can be a useful model to deeply understand mechanisms underlying the relationship between vitamin B and genome integrity.
Topics: Animals; DNA Damage; Disease Models, Animal; Drosophila; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Neoplasms; Vitamin B 6
PubMed: 32208818
DOI: 10.1098/rsob.200034 -
Nutrients Jun 2022Vitamin B6, B12 and folate are required for energy metabolism and have been identified as nutrients of concern for certain population groups. This study examined the...
Vitamin B6, B12 and folate are required for energy metabolism and have been identified as nutrients of concern for certain population groups. This study examined the cross-sectional association between the consumption of dairy (total dairy, milk, yogurt and cheese) and biomarkers and adequacy for these nutrients in a nationally representative sample. Twenty-four-hour dietary recall data and concentrations of RBC folate (ng/mL), serum folate (ng/mL), and serum vitamins B6 (nmol/L) and B12 (pg/mL) were obtained from the National Health and Nutrition Examination Survey 2001−2018 (n = 72,831) and were analyzed by linear and logistic regression after adjusting for demographic variables. Significance was set at p < 0.01. Mean intakes of total dairy were 2.21, 2.17, 1.83 and 1.51 cups eq among consumers aged 2−8, 9−18, 19−50 and 51+ years, respectively. Higher intakes of total dairy as well as individual dairy foods (especially milk and yogurt) were positively associated with serum and RBC folate, serum vitamin B6 and serum B12, and generally, with 9−57% lower risk of inadequate or deficient levels of these vitamins. These findings suggest that encouraging dairy consumption may be an effective strategy for improving micronutrient status and provide continued evidence to support the current dietary recommendations for dairy and dairy products.
Topics: Animals; Biomarkers; Cross-Sectional Studies; Folic Acid; Milk; Nutrition Surveys; Pyridoxine; Vitamin B 12; Vitamin B 6; Vitamins
PubMed: 35745171
DOI: 10.3390/nu14122441 -
Current Opinion in Biotechnology Apr 2017Vitamin B encompasses a group of related compounds (vitamers) that can only be biosynthesised de novo by plants and microorganisms. Enzymatic cofactor and antioxidant... (Review)
Review
Vitamin B encompasses a group of related compounds (vitamers) that can only be biosynthesised de novo by plants and microorganisms. Enzymatic cofactor and antioxidant functions for vitamin B are established in all kingdoms. Human vitamin B dietary insufficiency or genetic defects in B vitamer interconversion result in various neurological and inflammatory pathologies with several populations at-risk or marginal for vitamin B status. Three (rice, wheat and cassava) of the world's top five staple crops do not meet the recommended dietary allowance for vitamin B, when consumed as a major proportion of the diet. In addition, controlled enhancement of the appropriate B vitamer in crops has the potential to confer stress resistance. Thus, crop biofortification strategies represent an opportunity to reduce the risk of deficiency in populations with limited diet diversity and quality, as well as improving stress tolerance.
Topics: Biofortification; Crops, Agricultural; Humans; Vitamin B 6
PubMed: 28086191
DOI: 10.1016/j.copbio.2016.12.004 -
Current Topics in Medicinal Chemistry 2016There is growing evidence to suggest that chronic, low-grade inflammation occurs in abdominal obesity, insulin resistance, type 2 diabetes mellitus and related... (Review)
Review
There is growing evidence to suggest that chronic, low-grade inflammation occurs in abdominal obesity, insulin resistance, type 2 diabetes mellitus and related complications, and that proinflammatory cytokines play an important role in the onset and progression of type 2 diabetes. These findings consequently provide new opportunities for the use of anti-inflammatory strategies to correct the metabolic disorders. Discovery of new synthetic bioactive small molecules to interfere with chronic, low-grade inflammation and type 2 diabetes has attracted considerable attention in medicinal chemistry. To date, a number of organoselenium small molecules and chromium(III) complexes have been shown to have the potential to alleviate chronic low-grade inflammation and type 2 diabetes, including ebselen, selenomethionine, chromium picolinate, chromium dinicocysteinate, chromium phenylalaninate, trinuclear chromium propionate, chromium histidinate, chromium nicotinate, etc. Here, we review recent advances in development of organoselenium small molecules and chromium(III) complexes to intervene in chronic low-grade inflammation and type 2 diabetes, and discuss their mode of action, potential molecular mechanisms and toxicity.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Azoles; Chromium Compounds; Cysteine; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Inflammation; Isoindoles; Obesity; Organometallic Compounds; Organoselenium Compounds; Picolinic Acids; Small Molecule Libraries
PubMed: 26311428
DOI: 10.2174/1568026615666150827094815 -
Scandinavian Journal of Gastroenterology Jan 2019Bisacodyl and sodium picosulfate are classified both as stimulant laxatives, approved for short-term treatment of constipation and sold without prescription (OTC).... (Review)
Review
OBJECTIVES
Bisacodyl and sodium picosulfate are classified both as stimulant laxatives, approved for short-term treatment of constipation and sold without prescription (OTC). Stimulant laxatives are associated with harmful long-term colonic effects and possible carcinogenic risk - and evidence support that these agents are used for longer periods. We aimed to compile and review the clinical trial evidence describing the effectiveness and safety of long-term treatment (>14 continuous days) with stimulant laxatives.
METHODS
The PubMed database was searched for all randomised clinical trials (RCTs) examining the effect of bisacodyl or sodium picosulfate in adult patients diagnosed with constipation.
RESULTS
Five RCTs (one open-label and four double-blinded) with intervention periods of four weeks duration were eligible. These included 1008 patients, whereof 26% dropped out. A positive global assessment of efficacy was obtained in 78-99% of the patients treated with bisacodyl or sodium picosulfate. Notably, the same global assessment was obtained in 46-54% of the placebo-treated patients. Compared to placebo, an improvement in stool consistency and a significant increase in number of bowel movements peer week were seen in favor of bisacodyl and sodium picosulfate. However, for pyridostigmine, a significant difference was seen compared to bisacodyl. AEs were generally mild, but frequent (up to 72%) mostly diarrhea and abdominal pain.
CONCLUSION
The evidence base does not support use of stimulant laxatives for more than four weeks. Due to the substantial use of stimulant laxatives including sold OTC, longer term RCTs and epidemiological studies investigating effects and safety on the longer term are warranted.
Topics: Bisacodyl; Citrates; Colon; Constipation; Humans; Laxatives; Long-Term Care; Organometallic Compounds; Picolines; Randomized Controlled Trials as Topic
PubMed: 30700194
DOI: 10.1080/00365521.2018.1563806 -
European Journal of Paediatric... Jul 2018
Topics: Aldehyde Dehydrogenase; Epilepsy; Humans; Pyridoxine
PubMed: 29887411
DOI: 10.1016/j.ejpn.2018.05.004