BACKGROUND Autism spectrum disorder(ASD)presents unique challenges related to feeding and nutritional management.Children with ASD often experience feeding difficulties,including food selectivity,refusal,and gastroint...BACKGROUND Autism spectrum disorder(ASD)presents unique challenges related to feeding and nutritional management.Children with ASD often experience feeding difficulties,including food selectivity,refusal,and gastrointestinal issues.Various interventions have been explored to address these challenges,including dietary modifications,vitamin supplementation,feeding therapy,and behavioral interventions.AIM To provide a comprehensive overview of the current evidence on nutritional management in ASD.We examine the effectiveness of dietary interventions,vitamin supplements,feeding therapy,behavioral interventions,and mealtime practices in addressing the feeding challenges and nutritional needs of children with ASD.METHODS We systematically searched relevant literature up to June 2024,using databases such as PubMed,PsycINFO,and Scopus.Studies were included if they investigated dietary interventions,nutritional supplements,or behavioral strategies to improve feeding behaviors in children with ASD.We assessed the quality of the studies and synthesized findings on the impact of various interventions on feeding difficulties and nutritional outcomes.Data extraction focused on intervention types,study designs,participant characteristics,outcomes measured,and intervention effectiveness.RESULTS The review identified 316 studies that met the inclusion criteria.The evidence indicates that while dietary interventions and nutritional supplements may offer benefits in managing specific symptoms or deficiencies,the effectiveness of these approaches varies.Feeding therapy and behavioral interventions,including gradual exposure and positive reinforcement,promise to improve food acceptance and mealtime behaviors.The findings also highlight the importance of creating supportive mealtime environments tailored to the sensory and behavioral needs of children with ASD.CONCLUSION Nutritional management for children with ASD requires a multifaceted approach that includes dietary modifications,supplementation,feeding therapy,and behavioral strategies.The review underscores the need for personalized interventions and further research to refine treatment protocols and improve outcomes.Collaborative efforts among healthcare providers,educators,and families are essential to optimize this population's nutritional health and feeding practices.Enhancing our understanding of intervention sustainability and long-term outcomes is essential for optimizing care and improving the quality of life for children with ASD and their families.展开更多
AIM: To analyze a large population of patients with diabetes and peripheral neuropathy(PN) to determine other meaningful comorbid etiologies for PN.METHODS: Peripheral Neuropathy is a common complication of type 1 and...AIM: To analyze a large population of patients with diabetes and peripheral neuropathy(PN) to determine other meaningful comorbid etiologies for PN.METHODS: Peripheral Neuropathy is a common complication of type 1 and 2 diabetes mellitus;however,other potential causes for PN may be co-existing in patients with diabetes.A prospective cohort study was performed to assess patients with diabetes and PN.We compared patients having PN due solely to diabetes with patients possessing co-existing comorbidities,performing clinical(Toronto Clinical Scoring System and the Utah Early Neuropathy Scale),laboratory and electrophysiological assessments in all patients.RESULTS: Patients with either type 1 or 2 diabetes mellitus and co-existing comorbidities did not have more severe clinical or electrophysiological PN phenotypes overall.However,in patients with type 1 diabetes,presence of a lipid disorder was associated with greater PN severity.In type 2 diabetes patients,both a lipid disorder and cobalamin deficiency were associated with greater PN severity.There was no additive effect upon PN severity with presence of three or more comorbid etiologies.CONCLUSION: The presence of specific,and not general,comorbidities in patients with type 1 or 2 diabetes corresponds with greater PN severity.展开更多
Anemia is a frequent finding in most diseases which cause malabsorption. The most frequent etiology is the combination of iron and vitamin B12 deficiency. Celiac disease is frequently diagnosed in patients referred fo...Anemia is a frequent finding in most diseases which cause malabsorption. The most frequent etiology is the combination of iron and vitamin B12 deficiency. Celiac disease is frequently diagnosed in patients referred for evaluation of iron deficiency anemia (IDA), being reported in 1.8%-14.6% of patients. Therefore, duodenal biopsies should be taken during endoscopy if no obvious cause of iron defi ciency (ID) can be found. Cobalamin defi ciency occurs frequently among elderly patients, but it is often unrecognized because the clinical manifestations are subtle; it is caused primarily by food-cobalamin malabsorption and pernicious anemia. The classic treatment of cobalamin deficiency has been parenteral administration of the vitamin. Recent data suggest that alternative routes of cobalamin administration (oral and nasal) may be useful in some cases. Anemia is a frequent complication of gastrectomy, and has been often described after bariatric surgery. It has been shown that banding procedures which maintain digestive continuity with the antrum and duodenum are associated with low rates of ID. Helicobacter pylori (H pylori) infection may be considered as a risk factor for IDA, mainly in groups with high demands for iron, such as some children and adolescents. Further controlled trials are needed before making solid recommendations about H pylori eradication in these cases.展开更多
To date,metformin remains the first-line oral glucose-lowering drug used for the treatment of type 2 diabetes thanks to its well-established long-term safety and efficacy profile.Indeed,metformin is the most widely us...To date,metformin remains the first-line oral glucose-lowering drug used for the treatment of type 2 diabetes thanks to its well-established long-term safety and efficacy profile.Indeed,metformin is the most widely used oral insulinsensitizing agent,being prescribed to more than 100 million people worldwide,including patients with prediabetes,insulin resistance,and polycystic ovary syndrome.However,over the last decades several observational studies and meta-analyses have reported a significant association between long-term metformin therapy and an increased prevalence of vitamin B12 deficiency.Of note,evidence suggests that long-term and high-dose metformin therapy impairs vitamin B12 status.Vitamin B12(also referred to as cobalamin)is a water-soluble vitamin that is mainly obtained from animal-sourced foods.At the cellular level,vitamin B12 acts as a cofactor for enzymes that play a critical role in DNA synthesis and neuroprotection.Thus,vitamin B12 deficiency can lead to a number of clinical consequences that include hematologic abnormalities(e.g.,megaloblastic anemia and formation of hypersegmented neutrophils),progressive axonal demyelination and peripheral neuropathy.Nevertheless,no definite guidelines are currently available for vitamin B12 deficiency screening in patients on metformin therapy,and vitamin B12 deficiency remains frequently unrecognized in such individuals.Therefore,in this“field of vision”article we propose a list of criteria for a cost-effective vitamin B12 deficiency screening in metformin-treated patients,which could serve as a practical guide for identifying individuals at high risk for this condition.Moreover,we discuss additional relevant topics related to this field,including:(1)The lack of consensus about the exact definition of vitamin B12 deficiency;(2)The definition of reliable biomarkers of vitamin B12 status;(3)Causes of vitamin B12 deficiency other than metformin therapy that should be identified promptly in metformin-treated patients for a proper differential diagnosis;and(4)Potential pathophysiological mechanisms underlying metformin-induced vitamin B12 deficiency.Finally,we briefly review basic concepts related to vitamin B12 supplementation for the treatment of vitamin B12 deficiency,particularly when this condition is induced by metformin.展开更多
We evaluated whether the dodecylamine derivative of hydroxocobalamin acts as a potent inhibitor of cobalamin-dependent enzymes in an African green monkey kidney cell, COS-7. When the dodecylamine derivative (1.0 μmol...We evaluated whether the dodecylamine derivative of hydroxocobalamin acts as a potent inhibitor of cobalamin-dependent enzymes in an African green monkey kidney cell, COS-7. When the dodecylamine derivative (1.0 μmol/L) did not show any cytotoxicity in the cultured cells, the derivative could not affect methylmalonyl-CoA mutase (holo-enzyme) activity, but significantly inhibit methionine synthase (holo-enzyme) activity in the cell homogenates of COS-7 grown in 1.0 μmol/L hydroxocobalamin-supplemented medium. An immunoblot analysis indicated that the dodecylamine derivative could not decrease the protein level of methionine synthase, but significantly inhibit the enzyme activity.展开更多
We determined vitamin B12 content of Chinese black tea leaves using a microbiological assay based on Lactobacillus delbrueckii ATCC 7830. Trace levels (0.25 - 0.69 μg/100g dry weight) of vitamin B12 were detected in...We determined vitamin B12 content of Chinese black tea leaves using a microbiological assay based on Lactobacillus delbrueckii ATCC 7830. Trace levels (0.25 - 0.69 μg/100g dry weight) of vitamin B12 were detected in Pu’er, Fu, and Brick tea leaves. However, vitamin B12 content (0.06 - 1.37 μg/100g dry weight) of Ryubao tea leaves significantly varied. To determine whether Chinese black tea leaves contain vitamin B12 or other corrinoid compounds that are inactive in humans, corrinoid compounds were purified from Ryubao tea by an immunoaffinity column chromatography and vitamin B12 was identified by liquid chromatography-electrospray ionization/tandem mass spectrometry. Vitamin B12 content in the tea drink prepared from Ryubao tea leaves was very low (0.8 ng/100mL). Our results indicate that Chinese black tea is usually not a good source of B12, although Ryubao tea leaves with the highest B12 content may be utilized as a source of this vitamin for vegerarians.展开更多
Cobalamin uptake into cells is mediated by the CD320 receptor for transcobalamin-bound cobalamin. Optimum receptor expression is associated with proliferating cells and therefore, in many cancers this receptor express...Cobalamin uptake into cells is mediated by the CD320 receptor for transcobalamin-bound cobalamin. Optimum receptor expression is associated with proliferating cells and therefore, in many cancers this receptor expression is up regulated. Delivering drugs or toxins via this receptor provides increased targeting to cancer cells while minimizing toxicity to the normal tissues. Saporin conjugated monoclonal antibodies to the extracellular domain of TCblR were effectively internalized to deliver a toxic dose of Saporin to some cancer cell lines propagating in culture. Antibody concentration of 2.5 nM was effective in producing optimum inhibition of cell proliferation. The cytotoxic effect of mAb-Saporin appears to be dictated primarily by the level of receptor expression and therefore normal primary cells expressing low levels of CD320 were spared while tumor cell lines with higher CD320 expression were destroyed. Targeting the pathway for cellular uptake of vitamin B12 via the CD320 receptor with toxin-antibody conjugates appears to be a viable treatment strategy for certain cancers that over expresses this receptor.展开更多
Introduction Vitamin B12 is very vital for the nervous system. Its deficiency can manifest with neurological symptoms like pain and paresthesias and in severe cases may cause not completely restorable neurological dam...Introduction Vitamin B12 is very vital for the nervous system. Its deficiency can manifest with neurological symptoms like pain and paresthesias and in severe cases may cause not completely restorable neurological damage, especially in elderly patients. Methods The charts of 702 patients who underwent cervical spine surgery retrospectively reviewed and data collected . All patients were preoperatively seen by an internist who ordered Vit B12 levels for some of them. We used two thresholds for the diagnosis of vitamin B12 deficiency, 200 and 300 pg/mL as recommended by Yao et al. 1992. Data were also collected on gender, payor status, myelopathy, hemoglobin level, corpuscular parameters and glycosylated hemoglobin level (HbA1c). Vitamin B12 levels were compared between patients with HbA1c levels ≥ 6.1% and <6.1%. Differences between patients ≥ and < than the median age were studied. The median age of the patient cohort was 52. Results Hemoglobin level was recorded for 659 patients. Vit B12 levels were ordered for 291 patients only. Overall, 13.7% had decreased hemoglobin level (anemia), 30.2% had decreased Vit B12 levels by the 300 threshold, 6.9% had decreased Vit B12 levels by the 200 threshold, 6.3% decreased MCV (microcytosis), and 2.8% increased MCV (macrocytosis). Only four patients (0.7%), of whom older than 52, had decreased hemoglobin level and increased MCV (macrocytic anemia) and one patient (0.4%), who was also older than 52, had decreased hemoglobin level, increased MCV and Vit B12 level < 200 pg/mL (macrocytic anemia duo to Vit B12 deficiency). Dividing the patient sample into three age groups, <40, 40-59, and ≥ 60 years, we investigated the trend of cobalamin deficiency by age and found an increase in cobalamin deficiency after 40 from 0% to 7.4% (200 threshold). Uninsured patients (25%) using the 200 pg/mL threshold and workers’ compensation (54.5%) and uninsured patients (50.0%) had the highest rate of Vit B12 deficiency using the 300 pg/mL threshold. The few patients with macrocytic anemia (N=4) and macrocytic anemia due to Vit B12 deficiency (N=1) had health coverage. Conclusion Vit B12 deficiency in cervical spine surgery patients may not necessarily mean macrocytic anemia but may precede macrocytic anemia. Therefore, Vit B12 deficiency screening on the preoperative visit is warranted especially in uninsured or older patients or both. Preoperative treatment may be indicated and correlation with postoperative outcome is suggested for future research.展开更多
We read with great interest the excellent review by Wong et al on extra intestinal manifestations of Helicobacter pylori(H.pylori) infection published in the journal.This is a well-documented and structured review.How...We read with great interest the excellent review by Wong et al on extra intestinal manifestations of Helicobacter pylori(H.pylori) infection published in the journal.This is a well-documented and structured review.However,I believe that Wong et al failed to report the relationship between H.pylori infection and cobalamin.展开更多
Background:The present study was undertaken to investigate the clinical characteristics of hemolytic uremic syndrome(HUS)secondary to cobalamin C disorder(cbl-C disorder).Methods:We reviewed retrospectively the medica...Background:The present study was undertaken to investigate the clinical characteristics of hemolytic uremic syndrome(HUS)secondary to cobalamin C disorder(cbl-C disorder).Methods:We reviewed retrospectively the medical records of 3 children with HUS secondary to cbl-C disorder who had been treated between April 1,2009 and October 31,2013.Results:The 3 patients with HUS secondary to cbl-C disorder presented with progressive hemolytic anemia,acute renal failure,thrombocytopenia,poor feeding,and failure to thrive.Two of the 3 patients once had high blood pressure.The mutations of c.609G>A(P.W203X),c.217C>T(p.R73X)and c.365A>T(p.H122L)in the methylmalonic aciduria(cobalamin deficiency)cbl-C type,with homocystinuria gene were detected in the 3 patients.In these patients the levels of lactate dehydrogenase and homocysteine in serum were elevated and the level of methylmalonic acid(MMA)in urine was also elevated.After treatment with hydroxocobalamin,2 patients were discharged with no obvious abnormal growth and neurological development and 1 patient died of multiple organ failure.Conclusions:The results of this study demonstrated that cbl-C disorder should be investigated in any child presenting with HUS.The high concentrations of homocysteine and MMA could be used for timely recognization of the disease.Once the high levels of plasma homocystein and/or plasma or urine MMA are detected,the treatment with parenteral hydroxocobalamin should be prescribed immediately.The early diagnosis and treatment would contribute to the good prognosis of the disease.展开更多
Cobalamin is an essential human vitamin widely used in the pharmaceutical,food,and feed additive industries and currently produced by bacteria or archaea.Ensifer adhaerens HY-1 is an industrial strain that also produc...Cobalamin is an essential human vitamin widely used in the pharmaceutical,food,and feed additive industries and currently produced by bacteria or archaea.Ensifer adhaerens HY-1 is an industrial strain that also produces cobalamin.However production outputs are poor and the specific synthesis pathways require characterization.In this study,the whole genome sequence of E.adhaerens HY-1 was generated and annotated,and genes associated with cobalamin biosynthesis were identified.Then,three genes,CobSV,CobQ,and CobW were identified as the most efficient ones for enhancing cobalamin synthesis.By transcriptome sequencing of E.adhaerens HY-1 cells at different growth stages,65 endogenous promoters with different gradient strengths were identified.After combined expression of different strength promoters and key genes,a high cobalamin-producing recombinant strain,‘hmm’(genotype:PmetH-CobSV-PibpA-CobQ-Pmdh-CobW),was generated.Cobalamin production was 143.8 mg/L in shaking flasks,which was 41.0%higher than the original strain.Cobalamin production was further enhanced to 171.2 mg/L using fed-batch fermentation.Importantly,our data and novel approach provide important references for the analysis of cobalamin synthesis and other metabolites in complex metabolic pathways.展开更多
In this paper,the influence of two typical ionic impurities(Na_(+)and Mg_(2+))is investigated with the focused beam reflectance measurement(FBRM)technique.In this system,the on-line FBRM is used as a tool for monitori...In this paper,the influence of two typical ionic impurities(Na_(+)and Mg_(2+))is investigated with the focused beam reflectance measurement(FBRM)technique.In this system,the on-line FBRM is used as a tool for monitoring the crystallization process of cobalamin by measuring the chord length distribution of particles and the particle counts.It is noted that impurity Mg_(2+)has a more significant effect than Na_(2+)in crystal growth of the whole crystallization process.From the microscopic observation of crystals,Mg_(2+)has an obvious effect on the crystal habit,while Na_(2+)has little effect.In addition,the crystal habit changes can be monitored by particle vision measurement(PVM).Understanding these effects is helpful to aid optimization and improve process control.展开更多
Two new coenzyme B12 analogues, 2',5'-dideoxycytidylcobalamin (2a) and 2',5'-dide-oxyuridinylcobalamin (2b), and two others, 2',5'-dideoxyadenosylcobalamin (2c), and 5'-deoxy-thymidylcobala...Two new coenzyme B12 analogues, 2',5'-dideoxycytidylcobalamin (2a) and 2',5'-dide-oxyuridinylcobalamin (2b), and two others, 2',5'-dideoxyadenosylcobalamin (2c), and 5'-deoxy-thymidylcobalamin (2d) were prepared by an improved method. All the four analogues were investigated by UV-vis and 2D 1H NMR spectroscopy. The comparisons and discussion about their spectroscopic properties were done.展开更多
Dinoflagellates are responsible for most marine harmful algal blooms (HABs) and play vital roles in many ocean processes.More than 90% of dinoflagellates are vitamin B_(12) auxotrophs and that B_(12) availability can ...Dinoflagellates are responsible for most marine harmful algal blooms (HABs) and play vital roles in many ocean processes.More than 90% of dinoflagellates are vitamin B_(12) auxotrophs and that B_(12) availability can control dinoflagellate HABs,yet the genetic basis of B_(12) auxotrophy in dinoflagellates in the framework of the ecology of dinoflagellates and particularly HABs,which was the objective of this work.Here,we investigated the presence,phylogeny,and transcription of two methionine synthase genes(B_(12)-dependent metH and B_(12)-independent metE)via searching and assembling transcripts and genes from transcriptomic and genomic databases,cloning 38 cDNA isoforms of the two genes from 14 strains of dinoflagellates,measuring the expression at different scenarios of B_(12),and comprehensive phylogenetic analyses of more than 100 organisms.We found that 1)metH was present in all 58 dinoflagellates accessible and metE was present in 40 of 58 species,2)all metE genes lacked N-terminal domains,3)metE of dinoflagellates were phylogenetically distinct from other known metE genes,and 4)expression of metH in dinoflagellates was responsive to exogenous B_(12) levels while expression of metE was not responding as that of genuine metE genes.We conclude that most,hypothetically all,dinoflagellates have either non-functional metE genes lacking N-terminal domain for most species,or do not possess metE for other species,which provides the genetic basis for the widespread nature of B_(12) auxotrophy in dinoflagellates.The work elucidated a fundamental aspect of the nutritional ecology of dinoflagellates.展开更多
文摘BACKGROUND Autism spectrum disorder(ASD)presents unique challenges related to feeding and nutritional management.Children with ASD often experience feeding difficulties,including food selectivity,refusal,and gastrointestinal issues.Various interventions have been explored to address these challenges,including dietary modifications,vitamin supplementation,feeding therapy,and behavioral interventions.AIM To provide a comprehensive overview of the current evidence on nutritional management in ASD.We examine the effectiveness of dietary interventions,vitamin supplements,feeding therapy,behavioral interventions,and mealtime practices in addressing the feeding challenges and nutritional needs of children with ASD.METHODS We systematically searched relevant literature up to June 2024,using databases such as PubMed,PsycINFO,and Scopus.Studies were included if they investigated dietary interventions,nutritional supplements,or behavioral strategies to improve feeding behaviors in children with ASD.We assessed the quality of the studies and synthesized findings on the impact of various interventions on feeding difficulties and nutritional outcomes.Data extraction focused on intervention types,study designs,participant characteristics,outcomes measured,and intervention effectiveness.RESULTS The review identified 316 studies that met the inclusion criteria.The evidence indicates that while dietary interventions and nutritional supplements may offer benefits in managing specific symptoms or deficiencies,the effectiveness of these approaches varies.Feeding therapy and behavioral interventions,including gradual exposure and positive reinforcement,promise to improve food acceptance and mealtime behaviors.The findings also highlight the importance of creating supportive mealtime environments tailored to the sensory and behavioral needs of children with ASD.CONCLUSION Nutritional management for children with ASD requires a multifaceted approach that includes dietary modifications,supplementation,feeding therapy,and behavioral strategies.The review underscores the need for personalized interventions and further research to refine treatment protocols and improve outcomes.Collaborative efforts among healthcare providers,educators,and families are essential to optimize this population's nutritional health and feeding practices.Enhancing our understanding of intervention sustainability and long-term outcomes is essential for optimizing care and improving the quality of life for children with ASD and their families.
文摘AIM: To analyze a large population of patients with diabetes and peripheral neuropathy(PN) to determine other meaningful comorbid etiologies for PN.METHODS: Peripheral Neuropathy is a common complication of type 1 and 2 diabetes mellitus;however,other potential causes for PN may be co-existing in patients with diabetes.A prospective cohort study was performed to assess patients with diabetes and PN.We compared patients having PN due solely to diabetes with patients possessing co-existing comorbidities,performing clinical(Toronto Clinical Scoring System and the Utah Early Neuropathy Scale),laboratory and electrophysiological assessments in all patients.RESULTS: Patients with either type 1 or 2 diabetes mellitus and co-existing comorbidities did not have more severe clinical or electrophysiological PN phenotypes overall.However,in patients with type 1 diabetes,presence of a lipid disorder was associated with greater PN severity.In type 2 diabetes patients,both a lipid disorder and cobalamin deficiency were associated with greater PN severity.There was no additive effect upon PN severity with presence of three or more comorbid etiologies.CONCLUSION: The presence of specific,and not general,comorbidities in patients with type 1 or 2 diabetes corresponds with greater PN severity.
文摘Anemia is a frequent finding in most diseases which cause malabsorption. The most frequent etiology is the combination of iron and vitamin B12 deficiency. Celiac disease is frequently diagnosed in patients referred for evaluation of iron deficiency anemia (IDA), being reported in 1.8%-14.6% of patients. Therefore, duodenal biopsies should be taken during endoscopy if no obvious cause of iron defi ciency (ID) can be found. Cobalamin defi ciency occurs frequently among elderly patients, but it is often unrecognized because the clinical manifestations are subtle; it is caused primarily by food-cobalamin malabsorption and pernicious anemia. The classic treatment of cobalamin deficiency has been parenteral administration of the vitamin. Recent data suggest that alternative routes of cobalamin administration (oral and nasal) may be useful in some cases. Anemia is a frequent complication of gastrectomy, and has been often described after bariatric surgery. It has been shown that banding procedures which maintain digestive continuity with the antrum and duodenum are associated with low rates of ID. Helicobacter pylori (H pylori) infection may be considered as a risk factor for IDA, mainly in groups with high demands for iron, such as some children and adolescents. Further controlled trials are needed before making solid recommendations about H pylori eradication in these cases.
文摘To date,metformin remains the first-line oral glucose-lowering drug used for the treatment of type 2 diabetes thanks to its well-established long-term safety and efficacy profile.Indeed,metformin is the most widely used oral insulinsensitizing agent,being prescribed to more than 100 million people worldwide,including patients with prediabetes,insulin resistance,and polycystic ovary syndrome.However,over the last decades several observational studies and meta-analyses have reported a significant association between long-term metformin therapy and an increased prevalence of vitamin B12 deficiency.Of note,evidence suggests that long-term and high-dose metformin therapy impairs vitamin B12 status.Vitamin B12(also referred to as cobalamin)is a water-soluble vitamin that is mainly obtained from animal-sourced foods.At the cellular level,vitamin B12 acts as a cofactor for enzymes that play a critical role in DNA synthesis and neuroprotection.Thus,vitamin B12 deficiency can lead to a number of clinical consequences that include hematologic abnormalities(e.g.,megaloblastic anemia and formation of hypersegmented neutrophils),progressive axonal demyelination and peripheral neuropathy.Nevertheless,no definite guidelines are currently available for vitamin B12 deficiency screening in patients on metformin therapy,and vitamin B12 deficiency remains frequently unrecognized in such individuals.Therefore,in this“field of vision”article we propose a list of criteria for a cost-effective vitamin B12 deficiency screening in metformin-treated patients,which could serve as a practical guide for identifying individuals at high risk for this condition.Moreover,we discuss additional relevant topics related to this field,including:(1)The lack of consensus about the exact definition of vitamin B12 deficiency;(2)The definition of reliable biomarkers of vitamin B12 status;(3)Causes of vitamin B12 deficiency other than metformin therapy that should be identified promptly in metformin-treated patients for a proper differential diagnosis;and(4)Potential pathophysiological mechanisms underlying metformin-induced vitamin B12 deficiency.Finally,we briefly review basic concepts related to vitamin B12 supplementation for the treatment of vitamin B12 deficiency,particularly when this condition is induced by metformin.
文摘We evaluated whether the dodecylamine derivative of hydroxocobalamin acts as a potent inhibitor of cobalamin-dependent enzymes in an African green monkey kidney cell, COS-7. When the dodecylamine derivative (1.0 μmol/L) did not show any cytotoxicity in the cultured cells, the derivative could not affect methylmalonyl-CoA mutase (holo-enzyme) activity, but significantly inhibit methionine synthase (holo-enzyme) activity in the cell homogenates of COS-7 grown in 1.0 μmol/L hydroxocobalamin-supplemented medium. An immunoblot analysis indicated that the dodecylamine derivative could not decrease the protein level of methionine synthase, but significantly inhibit the enzyme activity.
文摘We determined vitamin B12 content of Chinese black tea leaves using a microbiological assay based on Lactobacillus delbrueckii ATCC 7830. Trace levels (0.25 - 0.69 μg/100g dry weight) of vitamin B12 were detected in Pu’er, Fu, and Brick tea leaves. However, vitamin B12 content (0.06 - 1.37 μg/100g dry weight) of Ryubao tea leaves significantly varied. To determine whether Chinese black tea leaves contain vitamin B12 or other corrinoid compounds that are inactive in humans, corrinoid compounds were purified from Ryubao tea by an immunoaffinity column chromatography and vitamin B12 was identified by liquid chromatography-electrospray ionization/tandem mass spectrometry. Vitamin B12 content in the tea drink prepared from Ryubao tea leaves was very low (0.8 ng/100mL). Our results indicate that Chinese black tea is usually not a good source of B12, although Ryubao tea leaves with the highest B12 content may be utilized as a source of this vitamin for vegerarians.
文摘Cobalamin uptake into cells is mediated by the CD320 receptor for transcobalamin-bound cobalamin. Optimum receptor expression is associated with proliferating cells and therefore, in many cancers this receptor expression is up regulated. Delivering drugs or toxins via this receptor provides increased targeting to cancer cells while minimizing toxicity to the normal tissues. Saporin conjugated monoclonal antibodies to the extracellular domain of TCblR were effectively internalized to deliver a toxic dose of Saporin to some cancer cell lines propagating in culture. Antibody concentration of 2.5 nM was effective in producing optimum inhibition of cell proliferation. The cytotoxic effect of mAb-Saporin appears to be dictated primarily by the level of receptor expression and therefore normal primary cells expressing low levels of CD320 were spared while tumor cell lines with higher CD320 expression were destroyed. Targeting the pathway for cellular uptake of vitamin B12 via the CD320 receptor with toxin-antibody conjugates appears to be a viable treatment strategy for certain cancers that over expresses this receptor.
文摘Introduction Vitamin B12 is very vital for the nervous system. Its deficiency can manifest with neurological symptoms like pain and paresthesias and in severe cases may cause not completely restorable neurological damage, especially in elderly patients. Methods The charts of 702 patients who underwent cervical spine surgery retrospectively reviewed and data collected . All patients were preoperatively seen by an internist who ordered Vit B12 levels for some of them. We used two thresholds for the diagnosis of vitamin B12 deficiency, 200 and 300 pg/mL as recommended by Yao et al. 1992. Data were also collected on gender, payor status, myelopathy, hemoglobin level, corpuscular parameters and glycosylated hemoglobin level (HbA1c). Vitamin B12 levels were compared between patients with HbA1c levels ≥ 6.1% and <6.1%. Differences between patients ≥ and < than the median age were studied. The median age of the patient cohort was 52. Results Hemoglobin level was recorded for 659 patients. Vit B12 levels were ordered for 291 patients only. Overall, 13.7% had decreased hemoglobin level (anemia), 30.2% had decreased Vit B12 levels by the 300 threshold, 6.9% had decreased Vit B12 levels by the 200 threshold, 6.3% decreased MCV (microcytosis), and 2.8% increased MCV (macrocytosis). Only four patients (0.7%), of whom older than 52, had decreased hemoglobin level and increased MCV (macrocytic anemia) and one patient (0.4%), who was also older than 52, had decreased hemoglobin level, increased MCV and Vit B12 level < 200 pg/mL (macrocytic anemia duo to Vit B12 deficiency). Dividing the patient sample into three age groups, <40, 40-59, and ≥ 60 years, we investigated the trend of cobalamin deficiency by age and found an increase in cobalamin deficiency after 40 from 0% to 7.4% (200 threshold). Uninsured patients (25%) using the 200 pg/mL threshold and workers’ compensation (54.5%) and uninsured patients (50.0%) had the highest rate of Vit B12 deficiency using the 300 pg/mL threshold. The few patients with macrocytic anemia (N=4) and macrocytic anemia due to Vit B12 deficiency (N=1) had health coverage. Conclusion Vit B12 deficiency in cervical spine surgery patients may not necessarily mean macrocytic anemia but may precede macrocytic anemia. Therefore, Vit B12 deficiency screening on the preoperative visit is warranted especially in uninsured or older patients or both. Preoperative treatment may be indicated and correlation with postoperative outcome is suggested for future research.
文摘We read with great interest the excellent review by Wong et al on extra intestinal manifestations of Helicobacter pylori(H.pylori) infection published in the journal.This is a well-documented and structured review.However,I believe that Wong et al failed to report the relationship between H.pylori infection and cobalamin.
基金supported by a grant from the Special Program for Clinical Research of the Beijing Municipal Commission of Science and Technology and WU JIE PING Medical Foundation,China(Grant Z121107005112008)
文摘Background:The present study was undertaken to investigate the clinical characteristics of hemolytic uremic syndrome(HUS)secondary to cobalamin C disorder(cbl-C disorder).Methods:We reviewed retrospectively the medical records of 3 children with HUS secondary to cbl-C disorder who had been treated between April 1,2009 and October 31,2013.Results:The 3 patients with HUS secondary to cbl-C disorder presented with progressive hemolytic anemia,acute renal failure,thrombocytopenia,poor feeding,and failure to thrive.Two of the 3 patients once had high blood pressure.The mutations of c.609G>A(P.W203X),c.217C>T(p.R73X)and c.365A>T(p.H122L)in the methylmalonic aciduria(cobalamin deficiency)cbl-C type,with homocystinuria gene were detected in the 3 patients.In these patients the levels of lactate dehydrogenase and homocysteine in serum were elevated and the level of methylmalonic acid(MMA)in urine was also elevated.After treatment with hydroxocobalamin,2 patients were discharged with no obvious abnormal growth and neurological development and 1 patient died of multiple organ failure.Conclusions:The results of this study demonstrated that cbl-C disorder should be investigated in any child presenting with HUS.The high concentrations of homocysteine and MMA could be used for timely recognization of the disease.Once the high levels of plasma homocystein and/or plasma or urine MMA are detected,the treatment with parenteral hydroxocobalamin should be prescribed immediately.The early diagnosis and treatment would contribute to the good prognosis of the disease.
基金supported by the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(32021005)the National Science Fund for Excellent Young Scholars(21822806).
文摘Cobalamin is an essential human vitamin widely used in the pharmaceutical,food,and feed additive industries and currently produced by bacteria or archaea.Ensifer adhaerens HY-1 is an industrial strain that also produces cobalamin.However production outputs are poor and the specific synthesis pathways require characterization.In this study,the whole genome sequence of E.adhaerens HY-1 was generated and annotated,and genes associated with cobalamin biosynthesis were identified.Then,three genes,CobSV,CobQ,and CobW were identified as the most efficient ones for enhancing cobalamin synthesis.By transcriptome sequencing of E.adhaerens HY-1 cells at different growth stages,65 endogenous promoters with different gradient strengths were identified.After combined expression of different strength promoters and key genes,a high cobalamin-producing recombinant strain,‘hmm’(genotype:PmetH-CobSV-PibpA-CobQ-Pmdh-CobW),was generated.Cobalamin production was 143.8 mg/L in shaking flasks,which was 41.0%higher than the original strain.Cobalamin production was further enhanced to 171.2 mg/L using fed-batch fermentation.Importantly,our data and novel approach provide important references for the analysis of cobalamin synthesis and other metabolites in complex metabolic pathways.
基金the National Key Technologies R&D Program for financial support(No.2007BAI46B04).
文摘In this paper,the influence of two typical ionic impurities(Na_(+)and Mg_(2+))is investigated with the focused beam reflectance measurement(FBRM)technique.In this system,the on-line FBRM is used as a tool for monitoring the crystallization process of cobalamin by measuring the chord length distribution of particles and the particle counts.It is noted that impurity Mg_(2+)has a more significant effect than Na_(2+)in crystal growth of the whole crystallization process.From the microscopic observation of crystals,Mg_(2+)has an obvious effect on the crystal habit,while Na_(2+)has little effect.In addition,the crystal habit changes can be monitored by particle vision measurement(PVM).Understanding these effects is helpful to aid optimization and improve process control.
基金Project supported by the National Natural Science Foundation of China.
文摘Two new coenzyme B12 analogues, 2',5'-dideoxycytidylcobalamin (2a) and 2',5'-dide-oxyuridinylcobalamin (2b), and two others, 2',5'-dideoxyadenosylcobalamin (2c), and 5'-deoxy-thymidylcobalamin (2d) were prepared by an improved method. All the four analogues were investigated by UV-vis and 2D 1H NMR spectroscopy. The comparisons and discussion about their spectroscopic properties were done.
基金edge the financial support from the National Natural Science Foundation of China(Grant No.41776125)the Key Deployment Project of Centre for Ocean Mega-Research of Science,Chinese Academy of Sciences(Grant No.COMS2019Q09)+3 种基金the Science&Technology Basic Resources Investigation Program of China(Grant No.2018FY100200)National Natural Science Foundation of China(Grants Nos.41976134 and 61533011)the Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology(Qingdao)(Grant No.2018SDKJ0504-2)supported by the Chicago Community Trust.
文摘Dinoflagellates are responsible for most marine harmful algal blooms (HABs) and play vital roles in many ocean processes.More than 90% of dinoflagellates are vitamin B_(12) auxotrophs and that B_(12) availability can control dinoflagellate HABs,yet the genetic basis of B_(12) auxotrophy in dinoflagellates in the framework of the ecology of dinoflagellates and particularly HABs,which was the objective of this work.Here,we investigated the presence,phylogeny,and transcription of two methionine synthase genes(B_(12)-dependent metH and B_(12)-independent metE)via searching and assembling transcripts and genes from transcriptomic and genomic databases,cloning 38 cDNA isoforms of the two genes from 14 strains of dinoflagellates,measuring the expression at different scenarios of B_(12),and comprehensive phylogenetic analyses of more than 100 organisms.We found that 1)metH was present in all 58 dinoflagellates accessible and metE was present in 40 of 58 species,2)all metE genes lacked N-terminal domains,3)metE of dinoflagellates were phylogenetically distinct from other known metE genes,and 4)expression of metH in dinoflagellates was responsive to exogenous B_(12) levels while expression of metE was not responding as that of genuine metE genes.We conclude that most,hypothetically all,dinoflagellates have either non-functional metE genes lacking N-terminal domain for most species,or do not possess metE for other species,which provides the genetic basis for the widespread nature of B_(12) auxotrophy in dinoflagellates.The work elucidated a fundamental aspect of the nutritional ecology of dinoflagellates.
