Cobalamin Deficiency Research Articles

Methionine synthase supports tumour tetrahydrofolate pools.

Mammalian cells require activated folates to generate nucleotides for growth and division. The most abundant circulating folate species is 5-methyl tetrahydrofolate (5-methyl-THF), which is used to synthesize methionine from homocysteine via the cobalamin-dependent enzyme methionine synthase (MTR). Cobalamin deficiency traps folates as 5-methyl-THF. Here, we show using isotope tracing that methionine synthase is only a minor source of methionine in cell culture, tissues, or xenografted tumors. Instead, methionine synthase is required for cells to avoid folate trapping and assimilate 5-methyl-THF into other folate species. Under conditions of physiological extracellular folates, genetic MTR knockout in tumor cells leads to folate trapping, purine synthesis stalling, nucleotide depletion, and impaired growth in cell culture and as xenografts. These defects are rescued by free folate but not one-carbon unit supplementation. Thus, MTR plays a crucial role in liberating tetrahydrofolate for use in one-carbon metabolism.

EXOCRINE PANCREATIC INSUFFICIENCY-LIKE SYNDROME IN FOUR CAPTIVE TIGERS (PANTHERA TIGRIS).

Exocrine pancreatic insufficiency (EPI) is a condition characterized by a decreased synthesis and secretion of pancreatic enzymes, which results in weight loss, poor hair coat, and diarrhea. The diagnostic test of choice for EPI in domestic cats is feline serum trypsin-like immunoreactivity (fTLI). This paper details four tigers (Panthera tigris) with clinical signs compatible with EPI. On the basis of domestic cat reference ranges, fTLI assays for all four clinically affected tigers were diagnostic for EPI (median 1.0 µg/L; range 0.5-1.2 µg/L). All four tigers had a rapid clinical response to pancreatic enzyme supplementation. Serum from 10 clinically healthy tigers was submitted for the fTLI assay, for comparative purposes. The healthy tigers' fTLI assays were also within range for a diagnosis of EPI in domestic cats (median 3.1 µg/L; range 1.9-4.5 µg/L); however, clinically affected tigers had significantly lower serum fTLI concentrations than healthy tigers (P = 0.0058). Serum cobalamin was below the detection limit in both the affected and healthy tigers (<150 ng/L). Measuring fTLI appears to be a useful tool in the diagnosis of EPI-like syndrome in tigers. As in other species, EPI-like syndrome in tigers may also be associated with cobalamin deficiency.

CLINICOETIOLOGICAL EVALUATION OF THE PATIENTS OF MACROCYTIC ANEMIA PRESENTING AT A TERTIARY CARE CENTRE IN KUMAON REGION OF UTRRAKHAND

INTRODUCTION: Macrocytosis is common in various clinical settings and it is found in approximately 1.7– 3.6% of people admitted for care for any cause [1, 2, 3]. Macrocytic anemia is generally classified as megaloblastic or nonmegaloblastic anemia. The causes of macrocytosis fall into two groups: (a) deficiency of vitamin B12 (cobalamin) or folate (or rarely abnormalities of their metabolism) in which the bone marrow is megaloblastic and (b) other causes,in which the bone marrow is usually normoblastic.A high level of suspicion,proper elicitation of the history and thorough examination and investigation of the patient helps in the diagnosis of macrocytic anemia. AIM AND OBJECTIVES: To evaluate the etiology of macrocytic anemia at a tertiary care centre. To determine the etiology of macrocytic anemia.To evaluate clinical manifestations associated with macrocytic anemia. MATERIAL AND METHOD: This 21 month Cross sectional observational study was carried out in OPD/IPD Department of Medicine, Government Medical College Haldwani (Uttarakhand). Full clinical examination and information regarding alcohol intake, dietary habit, drug intake, thyroid disorder and other comorbid illnesses was obtained.All patients were investigated with a completeHaemogramLiver function tests Serum TSH fasting vitamin B12 was measured Ultrasound as and when required. RESULT: In this study106 patients were taken 58 (45.3% ) were male and 48(54.7%) were females. Mean age was 44.83+16.85 years.Hemoglobin and MCV was in the range of 6.42 ± 2.09,(108.24 ± 7.10) respectively .The majority of patient,28 (52.83%) had vit B12 level in the range of 101 – 200 pg/ml,The majority of patients,44 (41.1%) had LDH level in the range of 281 – 1000 IU/L . CONCLUSION: In this study, there was a preponderance of young people.Vegetarians were most susceptible to MA especially cobalamin deficiency. Nutritional deficiency was the most common cause of MA, followed by alcohol and alcoholic liver disease.Data regarding the magnitude of the problem in different parts of India and the factors that might influence its incidence were lacking. Macrocytic anemia must be considered in the differential diagnosis of patients presenting with pyrexia of unknown origin,mild icterus or pancytopenia.

Symposium Title: Viscera-Brain Axis and Mental Health

Cobalamin deficiency is a common disorder associated with numerous neuropsychiatric presentations. Prior literature addresses the neurocognitive and affective symptoms, which include psychotic presentations. We present the first reported case of an individual with isolated auditory and visual hallucinations in the absence of other neurocognitive, mood, or psychotic symptoms.Mr. C, a 74-year-old male with a psychiatric history of PTSD (in remission), presented to the emergency department with one month of gait instability, frequent urinary incontinence while sleeping, and near-daily auditory and visual hallucinations. Given hallucinations, psychiatry was consulted. Mr. C had no other active psychiatric symptoms at time of interview and demonstrated a high degree of insight about his hallucinations. There were no cognitive deficits, delusions, or confusion discernible on exam. Medical work-up was remarkable for vitamin B12 of 148 pg/mL (normal 200-900 pg/mL) and increased red cell distribution width of 17% (normal 11.5-14.5%) with normal folate. Cobalamin was replenished with a 1000 mcg injection of cyanocobalamin and daily oral supplementation (100 mcg). He experienced complete resolution of hallucinations over five days.Our case demonstrates that hallucinations can be a presenting symptom of cobalamin deficiency without other neurocognitive, psychotic, or mood symptoms. We will review the literature on psychosis and cobalamin deficiency, discuss the neurobiological explanations for neuropsychiatric effects of cobalamin deficiency, and provide diagnostic and treatment recommendations.Consultation-liaison psychiatrists should be aware of isolated auditory and visual hallucinations as a presentation of cobalamin deficiency since prompt treatment can lead to rapid resolution of symptoms.

A Research on the Mechanism of Excellent Social Belief of Learning Records, Affection, Driving out Laziness and Maintaining

Cobalamin deficiency is a common disorder associated with numerous neuropsychiatric presentations. Prior literature addresses the neurocognitive and affective symptoms, which include psychotic presentations. We present the first reported case of an individual with isolated auditory and visual hallucinations in the absence of other neurocognitive, mood, or psychotic symptoms.Mr. C, a 74-year-old male with a psychiatric history of PTSD (in remission), presented to the emergency department with one month of gait instability, frequent urinary incontinence while sleeping, and near-daily auditory and visual hallucinations. Given hallucinations, psychiatry was consulted. Mr. C had no other active psychiatric symptoms at time of interview and demonstrated a high degree of insight about his hallucinations. There were no cognitive deficits, delusions, or confusion discernible on exam. Medical work-up was remarkable for vitamin B12 of 148 pg/mL (normal 200-900 pg/mL) and increased red cell distribution width of 17% (normal 11.5-14.5%) with normal folate. Cobalamin was replenished with a 1000 mcg injection of cyanocobalamin and daily oral supplementation (100 mcg). He experienced complete resolution of hallucinations over five days.Our case demonstrates that hallucinations can be a presenting symptom of cobalamin deficiency without other neurocognitive, psychotic, or mood symptoms. We will review the literature on psychosis and cobalamin deficiency, discuss the neurobiological explanations for neuropsychiatric effects of cobalamin deficiency, and provide diagnostic and treatment recommendations.Consultation-liaison psychiatrists should be aware of isolated auditory and visual hallucinations as a presentation of cobalamin deficiency since prompt treatment can lead to rapid resolution of symptoms.

Endothelium-derived Microparticles Are Increased in Teenagers With Cobalamin Deficiency.

Vitamin B 12 (cobalamin) deficiency may be a significant cause of hyperhomocysteinemia, and high homocysteine (Hcy) levels are associated with an increased risk of cardiovascular disease. Endothelium-derived microparticles (EMPs) are a new marker in endothelial dysfunction and atherosclerosis, which play a role in cardiovascular diseases' pathogenesis. This study aimed to evaluate the EMPs, the markers of endothelial dysfunction and atherosclerosis, and lipid profile in teenagers with cobalamin deficiency. This prospective study included 143 teenagers, 75 vitamin B 12 deficient patients and 68 healthy controls between 11 and 18 years of age. Routine laboratory tests, hemogram, vitamin B 12 , folic acid, ferritin, Hcy, lipid profile and EMPs were examined and compared. EMP subgroups were analyzed by flow cytometry method according to the expression of membrane-specific antigens. The microparticles released from the endothelium studied were VE-cadherin (CD144), S-endo1 (CD146), and Endoglin (CD105). The present study demonstrates that circulating CD105+ EMP, CD144+ EMP, CD146+ EMPs, and Hcy were increased, and high-density lipoprotein (HDL) cholesterol was reduced in teenagers with cobalamin deficiency. Vitamin B 12 showed a negative correlation with EMPs and Hcy, positive correlation with folate and HDL. All EMPs showed a significant positive correlation with triglyceride, vitamin B 12 , and HDL. Vitamin B 12 deficiency may predispose to endothelial damage and atherosclerosis by increasing EMPs and harms lipid metabolism in the long term.

Abstract 1223: Simultaneous knockdown of CD320 and LRP2 receptors is selectively toxic to cancer cells but not normal cells

Abstract Designing effective therapies with selective toxicity in cancer cells is a priority of cancer research. Porphyrins are known to selectively accumulate in cancerous tissue, a feature that has been exploited in cancer diagnostics and therapeutics. The porphyrin TCPP is used in the CyPath® Lung test for diagnosis of lung cancer. During efforts to elucidate the mechanism by which TCPP selectively accumulates in cancer cells, we discovered that simultaneous knockdown of two LDLR-family receptors, CD320 and LRP2, was selectively cytotoxic to cancer cells and not to normal cells. CD320 is a receptor that internalizes the complex of cobalamin (Vitamin B12)/transcobalamin II. LRP2 is a receptor strongly expressed in the kidney which also internalizes the cobalamin/transcobalamin II complex, in addition to more than 50 other ligands. Cobalamin is the catalytic cofactor for the enzymes methionine synthase and methylmalonyl CoA mutase, which play direct and indirect roles in folate metabolism, nucleotide biosynthesis, DNA methylation, and metabolism of fatty acids and amino acids, which suggests that cobalamin deprivation might be particularly deleterious to metabolically active cancer cells. We designed siRNAs to effectively silence CD320 and LRP2 protein expression and transfected these siRNAs into normal and cancer cell lines using commercial transfection reagents. Effective gene knockdown (up to 90%) was confirmed by western blotting. Simultaneous siRNA knockdown of CD320 and LRP2 in normal fibroblasts did not affect their cell proliferation, as measured by the Cell Titer-GLO assay. However, knockdown of CD320 and LRP2 in cancer cell lines derived from diverse tissues (lung, breast, prostate, brain, and skin cancers) inhibited cell proliferation or killed the cells by up to 80%. Interestingly, in some cell lines, when either CD320 or LRP2 were silenced individually, a concurrent increase in protein expression of the other receptor was observed, suggesting that CD320 and LRP2 compensate for each other's function; hence, silencing both receptors is required for optimal cell killing. Ongoing studies will test the hypothesis that cobalamin deficiency is a mechanism for the selective cytotoxicity observed in cancer cells. Further studies include in vivo animal studies to study the effects on CD320 and LRP2 knockdown on human tumor xenograft models. In summary, we have found that inhibiting CD320 and LRP2 expression strongly and selectively inhibits cancer cell growth, leading to a promising therapeutic strategy for diverse cancers. Citation Format: David J. Elzi, William Bauta, Shao-Chiang Lai, Trisha Das, Shweta Mogare, Vivienne I. Rebel. Simultaneous knockdown of CD320 and LRP2 receptors is selectively toxic to cancer cells but not normal cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1223.

The marker of cobalamin deficiency, plasma methylmalonic acid, may help identifying lysosomal iron trapping in patients. Its possible utility for heart failure

Iron deficiency is known to aggravate the prognosis of patients with heart failure. Iron has functions in the mitochondrial respiratory chain. In patients with reduced mitochondrial respiration, the mitochondrial ratio between the level of nicotinamide adenine dinucleotide and its reduced form decreases. Due to the mitochondrial-lysosomal interplay, decreased mitochondrial respiration also leads to inhibition of lysosomal hydrolysis. As a result, cobalamin and iron will be trapped in lysosomes. This will, even if iron and cobalamin have been consumed and absorbed in sufficient amounts, lead to their functional deficiencies.1 Functional iron deficiency can further impede mitochondrial respiration. Increased plasma levels of methylmalonic acid were shown to predict all-cause and cardiovascular mortality in the general population. Treatments targeting mitochondrial and lysosomal function may correct the functional deficiencies and improve prognosis in a subgroup of patients with heart failure, notably those with skeletal muscle wasting. Methylmalonic acid levels may be used for monitoring response to treatment, thereby identifying patients of the subgroup in which disease outcome may improve.

Development, optimization and in-vivo evaluation of cyanocobalamin loaded orodispersible films using hot-melt extrusion technology: A quality by design (QbD) approach

Vitamin B12 deficiency is associated with high risks of cognitive decline, neuropathy, megaloblastic anaemia and depression. Therefore, there is a need to develop an innovative formulation of vitamin B12 to restore optimal serum vitamin B12 levels (200–900 pg/mL), particularly in dysphagia patients. The present investigation deals with developing novel cyanocobalamin-loaded orodispersible films (ODFs) using Soluplus® as a film-forming polymer by hot-melt extrusion technology and application of Box-Behnken statistical design for formulation and process optimization. The amount of Soluplus®, glycerine and menthol were the critical formulation variables influencing critical quality attributes of films such as tensile strength, disintegration time, dissolution and permeation rate. Satisfactory results were obtained from melt-extruded films when subjected to physicochemical characterization tests. All melt-extruded films exhibited immediate disintegration and complete dissolution within 10 min. Ex-vivo permeation studies disclosed better permeation of cyanocobalamin from melt-extruded films as compared to plain drug solution. SEM and AFM analysis showed the uniform distribution of cyanocobalamin throughout the surface of the optimized film. Raman spectroscopy confirmed the stability of cyanocobalamin after HME processing. A rabbit animal model was employed to determine the pharmacokinetics of ODFs and marketed Quicobal® film using LC-MS/MS bioanalytical method. The in-vivo bioavailability of cyanocobalamin from optimized ODFs and marketed product showed similar plasma concentration-time profiles. The stability studies showed no appreciable physicochemical change up to six months. In conclusion, the ODFs of cyanocobalamin could be a better alternative formulation strategy for achieving rapid oral bioavailability in cobalamin deficiency.

Pernicious anemia: Pathophysiology and diagnostic difficulties.

Pernicious anemia (PA) is the most common cause of vitamin B12 (cobalamin) deficiency anemia in the world. It is an autoimmune disease, comprising of salient features of autoimmune chronic atrophic gastritis (CAG) and cobalamin deficiency (CD). Although the anemia was first described as pernicious, it may well be controlled with vitamin B12 replacement. The onset and progression of PA is often insidious. Alternatively, patients may have no anemic symptoms since they become acclimatized to the subtle nature of the disease. Oftentimes, there is a possibility that the underlying disease may be missed unless a full blood count (FBC) is investigated, leading to hindrance in the treatment journey. Diagnostic challenges remain tangible for many practicing clinicians, since there is lack of reliable cobalamin assays to diagnose CD as well as clinical mimics, which simulate many other hematological conditions, such as myelodysplastic syndrome, acute leukemia, sideroblastic anemias, bone marrow failure states, thrombotic microangiopathy, and thromboembolism. Moreover, prompt recognition of the symptoms of CD is also vital, because some neurologic sequalae may become irreversible despite replenishing cobalamin. Herein, we discuss a literature review on the pathophysiology, challenging clinical presentations and diagnostic difficulties of PA. Since the cobalamin replacement therapy for PA is straightforward, it will not be discussed in this review.

Tongue disorders due to megaloblastic anaemia and its management: A case report.

The presence of megaloblasts and macrocytes in the bone marrow characterizes megaloblastic anaemia. Megaloblastic anaemia is the result of folate and vitamin B12 deficiency in more than 95% of cases. We hereby report a case of megaloblastic anaemia in a 23-year old female having glossitis and a burning sensation on the tongue. The blood picture showed megaloblastic anaemia and haematological tests confirmed the diagnosis. The patient positively responded to vitamin B12 and folic acid supplementation. The presence of oral signs and symptoms offer the dentist an opportunity to participate in the diagnosis of this condition. Early diagnosis is important to prevent deficiency. This paper explains the oral changes induced by dietary deficiency of cobalamin or folate in a patient with megaloblastic anaemia.&#x0D; Update Dent. Coll. j: 2021; 11 (1): 26-28

Vitamin Cobalamin deficiency in macrocytic anemia reporting at a Tertiary Care Hospital.

Objective: Determine the frequency of vitamin cobalamin deficiency in macrocytic anemia cases reporting at tertiary care hospital. Study Design: Cross Sectional study. Setting: Faculty of Medicine and Allied Medical Sciences, Isra University, Hyderabad, Sindh Pakistan. Period: January 2017 to October 2018. Material &amp; Methods: 450 cases of both genders, diagnosed as macrocytic- megaloblastic anemia were studied for the vitamin Cobalamin levels. Cases were collected through non- probability convenient sampling by inclusion and exclusion criteria. Consenting volunteers were asked for blood sampling. 5 mL blood was taken from ante – cubital fossa. Samples were centrifuged and sera were collected for the estimation of vitamin cobalamin by ELISA – assay kit. Continuous and categorical variables were entered in SPSS (version 21.0) and analyzed by Student t-test and Chi-square test respectively at 95% CI (P ≤ 0.05). Results: Male and female comprised 225 (43.3%) and 294 (56.6%) of 519 subjects. Male to female ratio was noted 1.30:1. MCV, MCH and MCHC show statistically significant difference between male and female (P&lt;0.05). MCV in male was 96.8±9.92 fl vs. 105.5±12.04 fl in female (P=0.0001). Normal cobalamin was noted in 15.2% (n= 79) and any type of cobalamin deficiency was noted in 84.7% (n= 440) (P=0.0001). Conclusion: The present study reports frequency of 84.7% Cobalamin deficiency in macrocytic anemia reporting at Indus Medical College Hospital. Further studies are recommended by the treating physicians.

Plasma Exosomes From Healthy Individuals Could Protect Against Hippocampal Neuron Injury Induced by MMACHC Variants in Cobalamin (cblC) Deficiency

Background: Methylmalonic acid (MMA) combined with homocysteine (HCY) limits the survival and function of neurons during the development of cobalamin C (cblC) deficiency, yet no effective medication currently exists to ameliorate the damage. Methods: We designed a novel second-tier assay utilizing ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Plasma exosomes were isolated by ultracentrifugation and identified by RT-qPCR assays combined with luciferase activity. Additionally, DNA sequencing followed by tandem mass spectrometry (MS/MS) was performed to characterize individuals with cblC deficiency. Findings: Two previously unreported variants (c.228_231del and c.626_627del) in the MMACHC gene were identified. Second-tier test were offered dramatic power in predicting cblC deficiency outcomes. By demonstrating a proof-of-concept for plasma exosomal therapy methodology, we found that plasma exosomes can penetrate the blood-brain barrier (BBB) with accumulation in the hippocampus, and healthy plasma exosomes substantially can reduce neuronal apoptosis and repaired neurological deficits in cells and mouse models. Mechanistically, plasma exosomal miR-382-5p bound to the 3’-untranslated region (UTR) with downregulating MMACHC target gene transcription. Interpretation: The second-tier approach reduced false positives by 92% in individuals with cblC deficiency. Challenges remain in newborn screeing, and plasma exosomes might be therapeutically exploited to improve neural recovery of cblC deficiency. Funding: This work was supported by grants from the National Natural Science Foundation of China (No. 81671164, 81171075); Postgraduate Research & Practice Innovation Program of Jiangsu Province (Grant number: KYCX19_2211); Jiangsu Province Maternal and Child Health Project (Grant number: F201912) and Xuzhou Science and Technology Program (Grant number: KC19028). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The protocol was reviewed and approved by the Ethics Committee of the Affiliated Xuzhou Maternity and Child Health Care Hospital of Xuzhou Medical University, the committee’s reference number: [2019] No.9.All animal experiments were conducted after the approval of the local animal care committees (License ID: SYXK(Su)2015- 0030) and in accordance with the guidelines of the animal facility of Xuzhou Medical University.

The Level of Serum Pepsinogen in Diagnosing and Evaluating the Severity of Subacute Combined Degeneration Due to Vitamin B12 Deficiency.

Subacute combined degeneration (SCD) is a neurological complication of cobalamin deficiency, which is usually caused by chronic autoimmune atrophic gastritis. Serum pepsinogen 1 and the ratio of pepsinogen 1/pepsinogen 2 (PG1/2) can reflect the severity of gastric atrophy.Objective: This work aims to investigate whether decreased serum PG1 and PG1/2 ratio are helpful in diagnosing SCD and reflecting the severity of SCD.Methods: We retrospectively analyzed the clinical and laboratory tests of 65 cases of SCD due to vitamin B12 deficiency and compared the laboratory parameters of SCD with 65 age- and sex-matched amyotrophic lateral sclerosis (ALS) patients.Results: PG1 and PG1/2 ratio were decreased in 80 and 52.3% of SCD patients, respectively. Compared to patients with PG1/2 ratio ≥3.0, patients with PG1/2 ratio <3.0 had more severe anemia, larger mean corpuscular volume (MCV), lower level of vitamin B12, higher folate and homocysteine (Hcy), more severe changes in somatosensory evoked potential (SEP), and higher rate of lesions in spinal MRI (P < 0.05). PG1 and PG1/2 ratio had inverse correlation with MCV and N20 latency in SEP examination (P < 0.05). PG1/2 ratio, RBC count, and Hcy were independent risk factors for SCD in logistic regression analyses. The ROC curve analysis revealed that the diagnostic accuracy of PG1 and PG1/2 ratio was 72.2 and 73.0%, respectively, while the cutoff values were 22.4 ng/ml and 2.43 for SCD, respectively.Conclusions: Decreased PG1 and PG1/2 ratio are helpful for the diagnosis and evaluation of the severity of SCD due to vitamin B12 deficiency.

Pyoderma gangrenosum and cobalamin deficiency in systemic lupus erythematosus: a rare but non fortuitous association

BackgroundPyoderma gangrenosum (PG) is an uncommon, idiopathic, ulcerative neutrophilic dermatosis. In many cases, PG is associated with a wide variety of different disorders but SLE in association with PG is relatively uncommon. In this article we present the case of a middle aged patient with PG as the initial clinical presentation of SLE. We also provide a brief review of cobalamin deficiency which occurred in our patient and evidence-based management options.Case presentationA 35 years old man presented with a 5 month history of debilitating painful lower limb and scrotal ulcers. This was associated with polyarthralgia and morning stiffness involving both hands. He also complained of swallowing difficulties. He had unintentional weight loss of 10 kg and fatigue. Physical examination revealed alopecia, multiple cervical lymphadenopathies, bilateral parotid gland enlargement and atrophic glossitis. There was Raynaud’s phenomenon noted over both hands and generalised hyper-pigmented fragile skin. Laboratory results disclosed anaemia, leukopenia, hyponatraemia and hypocortisolism. Detailed anaemic workup revealed low serum ferritin and cobalamin level. The autoimmune screen showed positive ANA, anti SmD1, anti SS-A/Ro 52, anti SSA/Ro 60, anti U1-snRNP with low complement levels. Upper gastrointestinal endoscopy with biopsies confirmed atrophic gastritis and duodenitis. Intrinsic factor antibodies and anti-tissue transglutaminase IgA were all negative. Punch biopsies of the leg ulcer showed neutrophilic dermatosis consistent with pyoderma gangrenosum. Based on the clinical findings and positive immunologic studies, he was diagnosed as systemic lupus erythematosus. His general condition improved substantially with commencement of corticosteroids, immunosuppressants and vitamin supplements.ConclusionsWe report a case of PG as the first manifestation of SLE which was treated successfully with immunosuppressants and vitamin supplements. Our report highlighted the need to consider connective tissue diseases such as SLE in a patient presenting with PG in order for appropriate treatment to be instituted thereby achieving a good outcome.

Cobalamin Deficiency In Children With Sickle Cell Disease: An Unanticipated Risk For Use Of Nitrous Oxide Gas

Cobalamin Deficiency In Children With Sickle Cell Disease: An Unanticipated Risk For Use Of Nitrous Oxide Gas

Cold Adaptation in Antarctic Notothenioids: Comparative Transcriptomics Reveals Novel Insights in the Peculiar Role of Gills and Highlights Signatures of Cobalamin Deficiency

Far from being devoid of life, Antarctic waters are home to Cryonotothenioidea, which represent one of the fascinating cases of evolutionary adaptation to extreme environmental conditions in vertebrates. Thanks to a series of unique morphological and physiological peculiarities, which include the paradigmatic case of loss of hemoglobin in the family Channichthyidae, these fish survive and thrive at sub-zero temperatures. While some of the distinctive features of such adaptations have been known for decades, our knowledge of their genetic and molecular bases is still limited. We generated a reference de novo assembly of the icefish Chionodraco hamatus transcriptome and used this resource for a large-scale comparative analysis among five red-blooded Cryonotothenioidea, the sub-Antarctic notothenioid Eleginops maclovinus and seven temperate teleost species. Our investigation targeted the gills, a tissue of primary importance for gaseous exchange, osmoregulation, ammonia excretion, and its role in fish immunity. One hundred and twenty genes were identified as significantly up-regulated in Antarctic species and surprisingly shared by red- and white-blooded notothenioids, unveiling several previously unreported molecular players that might have contributed to the evolutionary success of Cryonotothenioidea in Antarctica. In particular, we detected cobalamin deficiency signatures and discussed the possible biological implications of this condition concerning hematological alterations and the heavy parasitic loads typically observed in all Cryonotothenioidea.

Cobalamin Deficiency and the Presence of Gastrointestinal Symptoms in Patients with Chronic Urticaria

Despite the previously reported presence of systemic symptoms in patients with chronic urticaria, the frequency and characteristics of gastrointestinal symptoms have not been described in a Canadian population.

Response of Human Glioblastoma Cells to Vitamin B12 Deficiency: A Study Using the Non-Toxic Cobalamin Antagonist.

Simple SummaryThe most important biological function of vitamin B12 (cobalamin) is to accomplish DNA synthesis, which is necessary for cell division. Cobalamin deficiency may be especially acute for rapidly dividing cells, such as glioblastoma cells. Therefore, cobalamin antagonists offer a medicinal potential for developing anti-glioma agents. In the present study, we revealed, for the first time, that the induction of cobalamin deficiency by vitamin B12 antagonist with affinity to key transporter of cobalamins, inhibited glioblastoma cells growth and promoted cell cycle arrest. The effect was observed for non-toxic concentration of the agent, as demonstrated on zebrafish. Moreover, as compared to our previous study, the cytostatic effect of the agent was more pronounced in glioblastoma cells than in normal astrocytes. We believe that the study may become the basis for further in vitro and in vivo experiments concerning cobalamin deprivation as a potential therapeutic strategy for glioblastoma.The most important biological function of vitamin B12 is to accomplish DNA synthesis, which is necessary for cell division. Cobalamin deficiency may be especially acute for rapidly dividing cells, such as glioblastoma cells. Therefore, cobalamin antagonists offer a medicinal potential for developing anti-glioma agents. In the present study, we developed an in vitro model of cobalamin deficiency in glioblastoma cells. Long-term treatment of cells with the cobalamin analogue, hydroxycobalamin [c-lactam] (HCCL) was applied to induce an increase of hypocobalaminemia biomarker. Cytometric assays demonstrated that vitamin B12 promoted glioblastoma cells proliferation, whereas the treatment of cells with HCCL caused a dramatic inhibition of cell proliferation and an induction of cell cycle arrest at the G2/M phase. Vitamin B12 counteracted all the observed effects of HCCL. In the in silico study, we characterized the molecular interactions between HCCL and transcobalamin II (TCII). We have demonstrated that HCCL shares similar interactions with TCII as naturally occurring cobalamins and therefore may act as a competitive inhibitor of this key transporter protein. We assessed the impact of HCCL on the mortality or developmental malformations of zebrafish embryos. Collectively, our findings suggest that the use of cobalamin transport antagonists as potential anti-glioma agents would be worth exploring further.

Common Pitfalls in the Management of Patients with Micronutrient Deficiency: Keep in Mind the Stomach.

Micronutrient deficiencies are relatively common, in particular iron and cobalamin deficiency, and may potentially lead to life-threatening clinical consequences when not promptly recognized and treated, especially in elderly patients. The stomach plays an important role in the homeostasis of some important hematopoietic micronutrients like iron and cobalamin, and probably in others equally important such as ascorbic acid, calcium, and magnesium. A key role is played by the corpus oxyntic mucosa composed of parietal cells whose main function is gastric acid secretion and intrinsic factor production. Gastric acid secretion is necessary for the digestion and absorption of cobalamin and the absorption of iron, calcium, and probably magnesium, and is also essential for the absorption, secretion, and activation of ascorbic acid. Several pathological conditions such as Helicobacter pylori-related gastritis, corpus atrophic gastritis, as well as antisecretory drugs, and gastric surgery may interfere with the normal functioning of gastric oxyntic mucosa and micronutrients homeostasis. Investigation of the stomach by gastroscopy plus biopsies should always be considered in the management of patients with micronutrient deficiencies. The current review focuses on the physiological and pathophysiological aspects of gastric acid secretion and the role of the stomach in iron, cobalamin, calcium, and magnesium deficiency and ascorbate homeostasis.