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Background/Objectives: Homocysteine (Hcy) and iron are factors co-related with the progression of cardiovascular diseases. The vascular endothelium is an important barrier for physiological homeostasis, and its impairment initiates cardiovascular injury. However, the mechanism underlying Hcy-caused vascular endothelial cell injury and the participation of iron are not fully elucidated. This study aims to investigate the Hcy-induced vascular endothelial injury and iron metabolism dysfunction as well as the underlying molecular mechanism. Methods: Human umbilical vein endothelial cells (HUVECs) were employed as the experimental model to examine the Hcy-induced endothelial injury and its underlying mechanism via various biochemical assays. Results: Hcy suppressed the cell viability and proliferation and caused cell death in a concentration-dependent manner. Hcy induced cell cycle arrest, apoptosis, and autophagy as well as impairment of intracellular energy metabolism. Hcy disrupted the intracellular antioxidant system and mitochondrial function by increasing intracellular ROS, MDA and mitochondrial content, and decreasing the SOD activity and mitochondrial membrane potential. Hcy significantly reduced the GSH-Px activity along with the accumulation of intracellular GSH in a concentration-dependent manner. Ferroptosis inhibitors, Ferrostatin-1 (Fer-1), and Deferoxamine (DFO) significantly decreased the Hcy-caused cytotoxicity accompanied by a reduction in dysregulated mitochondria content, but only DFO ameliorated the elevation of intracellular ROS, and neither Fer-1 nor DFO affected the Hcy-caused reduction in intracellular ATP. In addition, Hcy decreased the intracellular concentration of iron, and supplementing Hcy with various concentrations of Fe3+ increased the cell viability and decreased the LDH release in a concentration-dependent manner. Hcy dramatically decreased the mRNA expression level of transferrin receptor while increasing the mRNA expression levels of transferrin, ferritin light chain, ferritin heavy chain, ferroportin, and SLC7A11. Moreover, Hcy suppressed the protein expression of phospho-Akt, phospho-mTOR, Beclin-1, LC3A/B, Nrf2, HO-1, phospho-MEK1/2, phospho-ERK1/2, and Caspase-3 in concentration- and time-dependent manners. Conclusions: Hcy-induced vascular endothelial injury is likely to be associated with apoptosis and autophagy, but not ferroptosis. The key underlying mechanisms are involved in the disruption of the intracellular antioxidant system and iron metabolism via regulation of PI3K/Akt/mTOR, MAPKs, Nrf2/HO-1, and iron metabolism. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency with which suspected pathogenic factors, including metals and metabolites that might contribute to Alzheimer's disease (AD), may be found in patients with cognitive impairment through commonly available blood tests. Methods: A variety of serum studies, including metals, ammonia, homocysteine, vitamin B12, folate, thyroid tests, metabolic products, and inflammatory markers, were measured in two cohorts: one meeting mild cognitive impairment (MCI) criteria and the other meeting mild-to-moderate dementia (DE) criteria. Medications these patients received were reviewed. Results: Metal abnormalities were detected in over half the subjects, including evidence of mercury, lead, and arsenic elevation as well as instances of excessive essential metals, iron (Fe), and copper. Some metal aberration was detected in 64% of the DE group and 66% of the MCI group. Females were more likely to have elevated copper, consistent with hormonal effects on copper excretion. Homocysteinemia was the most common abnormality, detected in 71% with DE and 67% with MCI, while methylmalonic acid was not elevated. Slight hyperammonemia was moderately common (38%) suggesting a hepatic factor in this subset. Findings of moderate insulin resistance were present in nearly half (44% DE, 52% MCI). Sixty of 65 (92%) had at least one abnormal biomarker and 60% had two or more. The most common drug taken by the total cohort was proton pump inhibitors at 22% DE and 38% MCI. Conclusions: This study suggests that both toxic metals and excessive vital metals such as copper and iron, as well as common metabolic and hepatic factors are detectable at both stages of MCI and DE. There appears to be a multiplicity of provocative factors leading to DE. Individualized interventions based on these parameters may be a means to reduce cognitive decline leading to DE. A more comprehensive prospective study of these environmental and metabolic factors with corrective early interventions appears warranted. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the effects of MTHFR C677T and A1298C genes as well as folate supplementation on the recurrence and improvement of ischemic stroke. METHODS: Patients with primary ischemic stroke and National Institutes of Health Stroke Neurological Deficiency Scale ( NIHSS) score from 6 to 19 points admitted to the 960th Hospital of Joint Logistics Support Force of PLA and Tai’an Central Hospital from Mar. 2018 to Feb. 2019 and Jun. 2021 to May 2022 were collected, those patients who received conventional secondary prevention after treatment and discharged from hospital were set as non-exposed group, and those patients who received folate orally (0. 4 mg for once, 3 times a day) based on conventional secondary prevention were set as exposed group. Patients in the non-exposed group and exposed group were paired according to the principle of proximity of NIHSS scores, with 117 cases in each group, which were tested for MTHFR rs677 and rs1298 genotypes. A cohort study was carried out to inspect the correlation between MTHFR gene polymorphisms and folate supplementation with stroke recurrence within 1 year and the decline degree of NIHSS scores within 1 year. RESULTS: The distribution of each genotype of MTHFR in both groups was in accordance with the Hardy-Weinberg law of genetic equilibrium. Logistic analysis showed that recurrence within 1 year in stroke patients was associated with higher NIHSS scores at the first attack ( P = 0. 042, OR = 3. 193, 95% CI = 1. 104-9. 238 ), while it was not associated with MTHFR gene polymorphisms and folate supplementation during secondary prevention. Results of multivariate linear regression showed that the decline degree of NIHSS scores within 1 year in stroke patients was associated with carrying both MTHFR C677T and A1298C genes ( P = 0. 040, 95% CI = 0. 081-3. 178 ) and with the complication of hyperhomocysteinemia (HHcy) at the first attack (P = 0. 046, 95%CI = 0. 021-4. 059), while it was not associated with folate supplementation during secondary prevention. CONCLUSIONS: Under the condition of conventional secondary prevention implementation, ischemic stroke recurrence is associated with the severity at the first attack and independent of MTHFR gene polymorphisms. MTHFR C677T and A1298C as well as HHcy worked against ischemic stroke recovery within a year, yet is not associated with folate supplementation. [ABSTRACT FROM AUTHOR]

Background/Objectives: Homocysteine (Hcy) and iron are factors co-related with the progression of cardiovascular diseases. The vascular endothelium is an important barrier for physiological homeostasis, and its impairment initiates cardiovascular injury. However, the mechanism underlying Hcy-caused vascular endothelial cell injury and the participation of iron are not fully elucidated. This study aims to investigate the Hcy-induced vascular endothelial injury and iron metabolism dysfunction as well as the underlying molecular mechanism. Methods: Human umbilical vein endothelial cells (HUVECs) were employed as the experimental model to examine the Hcy-induced endothelial injury and its underlying mechanism via various biochemical assays. Results: Hcy suppressed the cell viability and proliferation and caused cell death in a concentration-dependent manner. Hcy induced cell cycle arrest, apoptosis, and autophagy as well as impairment of intracellular energy metabolism. Hcy disrupted the intracellular antioxidant system and mitochondrial function by increasing intracellular ROS, MDA and mitochondrial content, and decreasing the SOD activity and mitochondrial membrane potential. Hcy significantly reduced the GSH-Px activity along with the accumulation of intracellular GSH in a concentration-dependent manner. Ferroptosis inhibitors, Ferrostatin-1 (Fer-1), and Deferoxamine (DFO) significantly decreased the Hcy-caused cytotoxicity accompanied by a reduction in dysregulated mitochondria content, but only DFO ameliorated the elevation of intracellular ROS, and neither Fer-1 nor DFO affected the Hcy-caused reduction in intracellular ATP. In addition, Hcy decreased the intracellular concentration of iron, and supplementing Hcy with various concentrations of Fe3+ increased the cell viability and decreased the LDH release in a concentration-dependent manner. Hcy dramatically decreased the mRNA expression level of transferrin receptor while increasing the mRNA expression levels of transferrin, ferritin light chain, ferritin heavy chain, ferroportin, and SLC7A11. Moreover, Hcy suppressed the protein expression of phospho-Akt, phospho-mTOR, Beclin-1, LC3A/B, Nrf2, HO-1, phospho-MEK1/2, phospho-ERK1/2, and Caspase-3 in concentration- and time-dependent manners. Conclusions: Hcy-induced vascular endothelial injury is likely to be associated with apoptosis and autophagy, but not ferroptosis. The key underlying mechanisms are involved in the disruption of the intracellular antioxidant system and iron metabolism via regulation of PI3K/Akt/mTOR, MAPKs, Nrf2/HO-1, and iron metabolism.

The perioperative neurocognitive disorder (PND) is a severe complication that affects millions of surgical patients each year. Homocysteine (Hcy) is known to increase the risk of developing PND in both young and elderly mice. However, whether Hcy alone can induce cognitive deficits in middle-aged mice (12-month-old), whether exercise can attenuate Hcy-induced hippocampus-related cognitive deficits after surgery through suppressing neuroinflammation, synaptic elimination, and the level of Hcy remains unknown. The present study aimed to answer these questions through testing the possibility of establishing a PND model using 12-month-old mice which received homocysteine injections before exploratory laparotomy and the therapeutic mechanism of exercise. In the present study, it was found that levels of serum homocysteine were age-dependently increased in mice with a significant difference between that of 18-month-old mice and 6-week, 6-month, and 12-month-old mice. PND occurred in 18-month but not in 12-month-old mice after exploratory laparotomy under isoflurane anesthesia. Intraperitoneal injection of Hcy for 3 consecutive days before surgery rendered 12-month-old mice to develop PND after abdominal laparotomy under isoflurane anesthesia at a minimal dosage of 20 mg/kg. Neuroinflammation and synaptic elimination was present in 12-month-old preoperative Hcy-injected mice. Preoperative voluntary wheel exercise could prevent PND in 12-month-old mice that have received Hcy injection before surgery, which might be related to the decreased level of serum Hcy. Activation of glial cells, proinflammatory phenotype markers and synaptic elimination were attenuated in the hippocampus of 12-month-old preoperative Hcy-injected mice by this exercise. These results provide direct evidence that hyperhomocysteinemia can induce postoperative cognitive deficits in middle-aged mice. Pre-surgery exercise can effectively prevent Hcy-precipitated postoperative cognitive dysfunction.

To study the biochemical, clinical and molecular characteristics of 5,10- methylenetetrahydrofolate reductase (MTHFR) deficiency in Pakistani patients from a single center. Medical charts, urine organic acid chromatograms, plasma methionine and Hcys levels, and molecular testing results of MTHFR gene of patients presenting at the Biochemical Genetics Clinic, AKUH from 2016 to 2022 were reviewed. Neonatal MTHFR deficiency was found in five patients. The median (IQR) age of symptom onset and diagnosis were 18 (8.5–22) and 26 (16.5–31) days. The median lag between symptom onset and diagnosis was 8 (4.5–12.5) days. The median age of treatment initiation and duration of treatment were 26 (16.5–49) and 32 (25.5–54) days. The most common clinical features were lethargy, poor feeding, and seizures. The MTHFR gene sequencing revealed homozygous variants p.K510K, p.R567*, and p.R157W. Renal insufficiency manifesting as elevated serum creatinine and responding to betaine therapy was noted in one patient. This has not been previously reported in neonatal MTHFR deficiency and may reflect engagement of alternate pathways of remethylation. Adult onset MTHFR deficiency was found in six patients, with a heterogeneous neurological presentation. The median lag between symptoms onset and diagnosis was 7 (3–11) years. MTHFR gene sequencing revealed homozygous variant p.A195V in five patients from one family and p.G261V in the other. Two of the five reported variants are novel that include p.R157W and p.G261V. Eleven patients of this rare disorder from a single center indicate the need for clinical awareness and appropriate biochemical evaluation to ensure optimal outcomes. [ABSTRACT FROM AUTHOR]

BackgroundThe most common disorder of the intracellular cobalamin metabolism pathway is the combined methylmalonic acidemia and homocysteinemia, cblC type (cblC). There is a variation in its clinical spectrum ranging from severe neonatal-onset forms that are highly fatal to later-onset forms which are milder. In this study, the first case of an asymptomatic Chinese woman with a defect in congenital cobalamin (cblC type) metabolism at prenatal diagnosis due to elevated homocysteine level is identified.Case presentationThe proband, a male child born to a 29-year-old G1P0 mother, admitted to local hospital with feeding disorder, intellectual disability, seizures, microcephaly, as well as heterophthalmos. The level of the urine methylmalonic was elevated. Equally found were increased blood propionylcarnitine (C3) and propionylcarnitine/free carnitine ratio (C3/C0) and decreased methionine levels. The plasma total homocysteine level was elevated at 101.04 μmol/L (normal < 15 μmol/L). The clinical diagnosis of combined methylmalonic acidemia and homocysteinemia was supported. Four years later, the mother of the boy married again and came to us for prenatal diagnosis exactly 15 weeks after her last menstrual period. Subsequently, there is an increase in the amniotic fluid methylmalonate. The level of the amniotic fluid total homocysteine was marginally high. A considerably elevated amniotic fluid C3 was equally observed. In addition, there is a respective significant increase in the plasma and urine total homocysteine at 31.96 and 39.35 μmol/L. After the sequencing of MMACHC genes, it is found that the boy, a proband carried a homozygous mutation of the MMACHC at c.658_660delAAG. While the boy's mother, she carries two mutations in MMACHC: c.658_660delAAG and c.617G>A. The fetus is a carrier of the MMACHC gene. Following the administration of routine treatment, the mother remained symptom-free in the course of pregnancy, and she gave birth to a healthy boy.ConclusionVariable and nonspecific symptoms characterized the cblC type of methylmalonic acidemia combined with homocysteinemia. Both biochemical assays and mutation analysis are recommended as crucial complementary techniques.

Myocardial infarction (MI) is a cardiovascular disease that occurs due to the blockage of the coronary artery. Subsequently, cardiac muscles receive a lower oxygen supply, which leads to the death of cardiac muscles. The etiology of MI is linked to various environmental, occupational, and genetic factors. Various studies have been conducted on the polymorphism of genes involved in MI. Previous studies have shown that different variants of the methylene tetrahydrofolate reductase (MTHFR) gene are involved in causing MI by altering the metabolism of folate and homocysteine. However, the genetic polymorphism of MTHFR C677T (rs1801133) and its association with MI in the presence of diabetes mellitus (DM) as a risk factor still needs to be investigated. This study recruited 300 participants who were divided into three groups, i.e., the control, MI, and MI-DM. The blood samples collected from the study participants were subjected to various biochemical tests and their clinical parameters were monitored. MTHFR C677T (rs1801133) genotyping was performed by Tetra ARMS PCR using predetermined primers. The MTHFR C677T (rs1801133) polymorphism was associated with MI in the presence of DM as a risk factor among the participants. The MTHFR C677T (rs1801133) T/T homozygous genotype was found to be significant among MI patients in the presence of DM as a risk factor. [ABSTRACT FROM AUTHOR]

Septoplasty is a common operative procedure in ENT for correction of nasal septal deformity. Rarely it may result into devastating complication like vision loss. This may be related to other causes apart from septoplasty. The author presents a 27 yrs old male admitted to our hospital for septoplasty, 1 h after septoplasty the patient suffered from unilateral vision loss. After thorough examination and investigation the vision loss was found to be due to homocysteinemia. Hence homocysteinemia is one of the rare cause of vision loss in post septoplasty. Thus this is a rare presentation. [ABSTRACT FROM AUTHOR]

Homocysteine, an intermediate amino acid, is involved in methionine metabolism, which is crucial for various physiological pathways, including protein synthesis and DNA methylation. Elevated levels of homocysteine have been implicated as both a modifiable and unmodifiable risk factor in cardiovascular disease, influencing atherosclerotic disease formation and hypercoagulability. Mechanisms linking elevated homocysteine levels to vascular occlusion involve endothelial dysfunction, inflammation, and enhanced thrombotic potential. We present the case of a 54-year-old female with hyperhomocysteinemia-induced hypercoagulability causing acute limb ischemia, necessitating below-knee amputation., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Finlayson et al.)

Combined methylmalonic acidemia and homocystinuria, is a rare autosomal recessive disorder due to defective intracellular cobalamin metabolism. We report an 18-year-old Chinese male who presented with hypermyotonia, seizures, and congenital heart diseases. Mutation analysis revealed c.365A>T and c.482 G>A mutations in the MMACHC gene, diagnosed with methylmalonic aciduria and homocystinuria (CblC type). After treatment with vitamin B12, L-carnitine, betaine, and folate, which resulted in an improvement in his clinical symptoms and laboratory values. This case emphasizes that inborn errors of metabolism should be considered for a teenager presenting with challenging or neurologic symptoms, especially when combined with unexplained heart diseases. [ABSTRACT FROM AUTHOR]

Methylmalonic acidemia is a rare autosomal recessive metabolic disease. However, because of the atypical clinical symptoms, the type of late-onset methylmalonic academia is often misdiagnosed. Especially when the blood vitamin B12 and folic acid levels are normal, it is not easy to think of this disease. Herein we report a 9-year-old girl who developed normally on a relatively balanced diet before 7 years of age. However, she presented with fatigue and attention deficit when she followed a vegetarian diet. Laboratory examination showed moderate macrocytic anemia, high levels of homocysteine, high level of propionylcarnitine/acetylcarnitine, urinary methylmalonic acid and methyl citrate. Gene mutation analysis showed c.609G > A and c.80A > G compound heterozygous mutations in the MMACHC gene, supported late-onset combined methylmalonic academia with homocysteinemia. Then treatment performed with add meat to the diet, vitamin B12, folic acid betaine and L-carnitine supplement. One week later, the child's clinical symptoms and the laboratory examinations were significantly improved.

Background: Methylmalonic acidemia (MMA) can display many clinical manifestations, among which acute lymphoblastic leukemia (ALL) has not been reported, and congenital heart disease (CHD) is also rare. Case presentation: We report an MMA case with ALL and CHD in a 5.5-year-old girl. With developmental delay and local brain atrophy in MRI, she was diagnosed with cerebral palsy at 9 months old. Rehabilitation was performed since then. This time she was admitted to hospital because of weakness and widespread bleeding spots. ALL-L2 (pre-B-cell) was confirmed by bone marrow morphology and immunophenotyping. Echocardiography showed patent foramen ovale. The girl was treated with VDLD and CAML chemotherapy, during which she developed seizures, edema and renal insufficiency. Decrease of muscle strength was also found in physical examination. Screening for inherited metabolic disorders showed significantly elevated levels of methylmalonate-2, acetylcarnitine (C2), propionylcarnitine (C3), C3/C2 and homocysteine. Gene analysis revealed a compound heterozygous mutaion in MMACHC (NM_015,560): c.80A > G (p.Gln27Arg) and c.609G > A (p.Trp203*). CblC type MMA was diagnosed. Intramuscular injection of cyanocobalamin and intravenous L-carnitine treatment were applied. The edema vanished gradually, and chemotherapy of small dosage of vindesine was given intermittently when condition permitted. 2 months later, muscle strength of both lower limbs were significantly improved to nearly grade 5. The levels of methylmalonic acid and homocysteine were improved. Conclusion: Metabolic disease screening and gene analysis are very necessary for diseases with complex clinical symptoms. ALL can be a rare manifestation for MMA. Synopsis: We report a case of methylmalonic acidemia with acute lymphoblastic leukemia and congenital heart disease, which uncovered the importance of genetic testing and metabolic diseases screening in patients with multiple systemic organ involvement. [ABSTRACT FROM AUTHOR]

Background: Methylmalonic acidemia (MMA) can display many clinical manifestations, among which acute lymphoblastic leukemia (ALL) has not been reported, and congenital heart disease (CHD) is also rare.Case presentation: We report an MMA case with ALL and CHD in a 5.5-year-old girl. With developmental delay and local brain atrophy in MRI, she was diagnosed with cerebral palsy at 9 months old. Rehabilitation was performed since then. This time she was admitted to hospital because of weakness and widespread bleeding spots. ALL-L2 (pre-B-cell) was confirmed by bone marrow morphology and immunophenotyping. Echocardiography showed patent foramen ovale. The girl was treated with VDLD and CAML chemotherapy, during which she developed seizures, edema and renal insufficiency. Decrease of muscle strength was also found in physical examination. Screening for inherited metabolic disorders showed significantly elevated levels of methylmalonate-2, acetylcarnitine (C2), propionylcarnitine (C3), C3/C2 and homocysteine. Gene analysis revealed a compound heterozygous mutaion in MMACHC (NM_015,560): c.80A > G (p.Gln27Arg) and c.609G > A (p.Trp203*). CblC type MMA was diagnosed. Intramuscular injection of cyanocobalamin and intravenous L-carnitine treatment were applied. The edema vanished gradually, and chemotherapy of small dosage of vindesine was given intermittently when condition permitted. 2 months later, muscle strength of both lower limbs were significantly improved to nearly grade 5. The levels of methylmalonic acid and homocysteine were improved.Conclusion: Metabolic disease screening and gene analysis are very necessary for diseases with complex clinical symptoms. ALL can be a rare manifestation for MMA.Synopsis: We report a case of methylmalonic acidemia with acute lymphoblastic leukemia and congenital heart disease, which uncovered the importance of genetic testing and metabolic diseases screening in patients with multiple systemic organ involvement.

Abstract Background Disorders of the metabolism and absorption of vitamin B12 can lead to decrease in activity of methionine synthetase and methylmalonate coenzyme A mutase (MMUT), which results in increased levels of methylmalonic acid and homocysteine in blood and urine. Often, combined methylmalonic acidemia (MMA) and homocysteinemia is misdiagnosed due to a lack of specific symptoms. The clinical manifestations are diverse, but proteinuria as the initial presentation is rare. Case presentation Two cases of MMA with homocysteinemia in children are reported. Proteinuria were a primary presenting symptom, followed by anemia and neurologic symptoms (frequent convulsions and unstable walking, respectively). Screening of amino acids and acyl carnitine in serum showed that the propionyl carnitine:acetylcarnitine ratio increased. Profiling of urinary organic acids by gas chromatography–mass spectrometry revealed high levels of methylmalonic acid. Homocysteine content in blood was increased. Comprehensive genetic analyses of peripheral blood-derived DNA demonstrated heterozygous variants of methylmalonic aciduria type C and homocystinuria (MMACHC) and amnionless (AMN) genes in our two patients, respectively. After active treatment, the clinical manifestations in Case 1 were relieved and urinary protein ceased to be observed; Case 2 had persistent proteinuria and was lost to follow-up. Conclusions Analyses of the organic acids in blood and urine suggested MMA combined with homocysteinemia. In such diseases, reports of renal damage are uncommon and proteinuria as the initial presentation is rare. Molecular analysis indicated two different genetic causes. Although the pathologic mechanisms were related to vitamin B12, the severity and prognosis of renal lesions were different. Therefore, gene detection provides new insights into inherited metabolic diseases.

Myocardial infarction (MI) is a cardiovascular disease that occurs due to the blockage of the coronary artery. Subsequently, cardiac muscles receive a lower oxygen supply, which leads to the death of cardiac muscles. The etiology of MI is linked to various environmental, occupational, and genetic factors. Various studies have been conducted on the polymorphism of genes involved in MI. Previous studies have shown that different variants of the methylene tetrahydrofolate reductase (MTHFR) gene are involved in causing MI by altering the metabolism of folate and homocysteine. However, the genetic polymorphism of MTHFR C677T (rs1801133) and its association with MI in the presence of diabetes mellitus (DM) as a risk factor still needs to be investigated. This study recruited 300 participants who were divided into three groups, i.e., the control, MI, and MI-DM. The blood samples collected from the study participants were subjected to various biochemical tests and their clinical parameters were monitored. MTHFR C677T (rs1801133) genotyping was performed by Tetra ARMS PCR using predetermined primers. The MTHFR C677T (rs1801133) polymorphism was associated with MI in the presence of DM as a risk factor among the participants. The MTHFR C677T (rs1801133) T/T homozygous genotype was found to be significant among MI patients in the presence of DM as a risk factor.

Hyperhomocysteinemia is a rare condition which predisposes to arterial and venous thrombosis. Plasma homocysteine levels are influenced by many genetic factors and environmental factors. Increased levels of homocysteine at high-altitude areas (HAA) can predispose to upper-extremity deep-vein thrombosis (UEDVT). Therefore, awareness by the medical authorities regarding this entity at HAA as a sole cause of UEDVT needs to be established. Prompt reduction in the homocysteine level can be therapeutic as well as prophylactic in preventing the morbidity.

There are not enough recent studies on arterial ischemic stroke (AIS) in Indian children. We retrospectively reviewed data on 95 children (69 boys), aged 3 months to 17 years, with AIS. Focal signs were noted in 84 (88%) with hemiparesis in 72 (76%). Diffuse signs were present in 33 (35%) with fever in 22 (23%), altered mental status in 20 (21%), and headache in 12 (13%). Seizures occurred in 29 (31%) children. Arteriopathy was observed in 57 (60%) children with mineralizing lenticulostriate vasculopathy (mLSV) in 22 (23%) being the most common, followed by moyamoya in 14 (15%), arterial dissection in 9 (10%), and focal cerebral arteriopathy (FCA) in 8 (8%). Preceding head/neck trauma was present in 27 (28%) children: 23 had minor head trauma (MHT), 3 neck trauma, and 1 unspecified. Other common risk factors (RFs) were iron deficiency in 10 children, homocysteinemia in 8 children, and tuberculous meningitis in 5 children. Complete or nearly complete recovery occurred in 42 (44%). Nine children developed epilepsy and five cognitive and language disability. Stroke recurrences occurred in nine children. Overall, arteriopathies accounted for majority of the cases of childhood AIS in our study with mLSV and moyamoya being the most frequent. Compared with data from Western countries, FCAs, postvaricella arteriopathy, and arterial dissections were less common. Of the nonarteriopathic RFs, MHT, iron deficiency, homocysteinemia, and neuroinfections were most frequent in our cohort in contrast to cardioembolic diseases and inherited procoagulant conditions, which are common in developed countries. [ABSTRACT FROM AUTHOR]

The perioperative neurocognitive disorder (PND) is a severe complication that affects millions of surgical patients each year. Homocysteine (Hcy) is known to increase the risk of developing PND in both young and elderly mice. However, whether Hcy alone can induce cognitive deficits in middle-aged mice (12-month-old), whether exercise can attenuate Hcy-induced hippocampus-related cognitive deficits after surgery through suppressing neuroinflammation, synaptic elimination, and the level of Hcy remains unknown. The present study aimed to answer these questions through testing the possibility of establishing a PND model using 12-month-old mice which received homocysteine injections before exploratory laparotomy and the therapeutic mechanism of exercise. In the present study, it was found that levels of serum homocysteine were age-dependently increased in mice with a significant difference between that of 18-month-old mice and 6-week, 6-month, and 12-month-old mice. PND occurred in 18-month but not in 12-month-old mice after exploratory laparotomy under isoflurane anesthesia. Intraperitoneal injection of Hcy for 3 consecutive days before surgery rendered 12-month-old mice to develop PND after abdominal laparotomy under isoflurane anesthesia at a minimal dosage of 20 mg/kg. Neuroinflammation and synaptic elimination was present in 12-month-old preoperative Hcy-injected mice. Preoperative voluntary wheel exercise could prevent PND in 12-month-old mice that have received Hcy injection before surgery, which might be related to the decreased level of serum Hcy. Activation of glial cells, proinflammatory phenotype markers and synaptic elimination were attenuated in the hippocampus of 12-month-old preoperative Hcy-injected mice by this exercise. These results provide direct evidence that hyperhomocysteinemia can induce postoperative cognitive deficits in middle-aged mice. Pre-surgery exercise can effectively prevent Hcy-precipitated postoperative cognitive dysfunction. • Levels of serum homocysteine were increased with age. • Hyperhomocysteinemia increases susceptibility of middle-aged mice to perioperative neurocognitive disorders. • Exercise decreases serum Hcy and prevents surgery induced hippocampal injury. [ABSTRACT FROM AUTHOR]

Background: Heart failure represents a major health problem leading to considerable mortality morbidity. High total homocysteine concentrations have been related to increased risk of atherosclerosis and its sequel, including coronary heart disease, cardiovascular mortality, and stroke. Brain Natriuretic peptide is a member of a group of peptide hormones similar in structure, used as a specific marker for diagnosing heart failure. This marker increases gradually with the progression of the grade of heart failure. Objective: The current study aims to measure and investigate the difference in the level of homocysteine between patients with heart failure and without, to find the relationship between the level of homocysteine and grade of heart failure, and to find out the correlation between homocysteine levels with Brain Natriuretic peptide levels. Patients and Methods: This case-control study involved 200 participants, 100 patients with a history of chronic heart failure, and 100 control participants.A self-constructed questionnaire form prepared to collect selected variables, the participant’s weight, height, temperature, electrocardiography measured by trained staff, Brain Natriuretic peptide used as a specific marker for diagnosing heart failure. Blood samples were taken early in the morning from the patient and control groups, after at least 12-hours of fasting and a 20-minute rest. Analysis of all samples of blood was performed in the Biochemistry Laboratory of Baqubah teaching hospital to measure the levels of homocysteine by Human Homocysteine ELISA kit. Results: The sample was selected homogenously in terms of age and gender. Overweight, obesity, current and ex-smoker, history of hypertension, and history of diabetes mellitus were significantly higher in patients with heart failure than control. The fasting mean homocysteine level was significantly higher in patients (20.049nmol/ml) than in control (2.734nmol/ml). The fasting mean homocysteine level was significantly elevated in the patients with a positive history of hypertension and diabetes mellitus (p-value ≤0.05) than patients with a negative history. The level of homocysteine was correlated significantly and positively with the level of Brain Natriuretic peptide(r=0.39, p=0.001). The fasting mean homocysteine level was significantly increased with an increase in the severity (grades) of the heart failure (p-value = 0.001). Conclusion: There was a relationship between the homocysteine level with the development, and severity (grades) of the heart failure as well as significantly and positively correlated with the Brain Natriuretic peptide level.

Methionine (MET) rich diets, smoking, coffee and alcohol consumption , low physical activity, and aging are related to high plasma concentrations of homocysteine, which can jeopardize the heart health. Although hyperhomocysteinemia has been considered a recognized risk factor for cardiac dysrhythmia, the structural changes of the conductive system, including Sinoatrial (SA) node of the heart involved in the disorder, have not been completely clarified. Curcumin is the main component of turmeric and has shown some cardioprotective effects. This study aimed to evaluate the effect of curcumin on the structural changes of the SA node in L-MET-treated rats. These alterations were evaluated by means of stereological techniques, namely cavalieri principle for volume estimation and optical disector counting technique for cell counting. Both techniques used two-dimensional images for obtaining three-dimensional parameters. The rats were divided into four groups, including control, MET-treated (1 g/kg/day), curcumin-treated, (100 mg/kg/day), and MET + curcumin. The treatments were performed for 28 days. On the final day, SA nodes were dissected out for stereological investigation. Compared to the control rats, the volume of SA node, total volume of grape-like cell clusters, and number of SA node cells were respectively decreased by 42%, 34%, and 37% in the MET-treated group (p < 0.04). However, collagen density remained constant in all the study groups. Furthermore, treatment with curcumin could protect the SA node from cellular decline in the MET + curcumin group (p < 0.01). It can be concluded that curcumin could prevent the structural changes of the SA node in the rats treated with methionine. [ABSTRACT FROM AUTHOR]

Background: Heart failure represents a major health problem leading to considerable mortality morbidity. High total homocysteine concentrations have been related to increased risk of atherosclerosis and its sequel, including coronary heart disease, cardiovascular mortality, and stroke. Brain Natriuretic peptide is a member of a group of peptide hormones similar in structure, used as a specific marker for diagnosing heart failure. This marker increases gradually with the progression of the grade of heart failure. Objective: The current study aims to measure and investigate the difference in the level of homocysteine between patients with heart failure and without, to find the relationship between the level of homocysteine and grade of heart failure, and to find out the correlation between homocysteine levels with Brain Natriuretic peptide levels. Patients and Methods: This case-control study involved 200 participants, 100 patients with a history of chronic heart failure, and 100 control participants.A self-constructed questionnaire form prepared to collect selected variables, the participant's weight, height, temperature, electrocardiography measured by trained staff, Brain Natriuretic peptide used as a specific marker for diagnosing heart failure. Blood samples were taken early in the morning from the patient and control groups, after at least 12-hours of fasting and a 20-minute rest. Analysis of all samples of blood was performed in the Biochemistry Laboratory of Baqubah teaching hospital to measure the levels of homocysteine by Human Homocysteine ELISA kit. Results: The sample was selected homogenously in terms of age and gender. Overweight, obesity, current and ex-smoker, history of hypertension, and history of diabetes mellitus were significantly higher in patients with heart failure than control. The fasting mean homocysteine level was significantly higher in patients (20.049nmol/ml) than in control (2.734nmol/ml). The fasting mean homocysteine level was significantly elevated in the patients with a positive history of hypertension and diabetes mellitus (p-value =0.05) than patients with a negative history. The level of homocysteine was correlated significantly and positively with the level of Brain Natriuretic peptide(r=0.39, p=0.001). The fasting mean homocysteine level was significantly increased with an increase in the severity (grades) of the heart failure (p-value = 0.001). Conclusion: There was a relationship between the homocysteine level with the development, and severity (grades) of the heart failure as well as significantly and positively correlated with the Brain Natriuretic peptide level. [ABSTRACT FROM AUTHOR]

Introduction: Lipid metabolism disorder or hyperlipidemia is known as a risk factor for cardiovascular disease, the increase in serum homocysteine and leptin are associated with atherosclerotic disease. The purpose of the present study was to examine the effects of bovine lactoferrin (bLF) on serum homocysteine (Hcy), apolipoproteinA-I (ApoA-I) and B (ApoB), leptin and lipid profile changes in high-cholesterol-diet (HCD) fed rats. Methods: The Healthy Adult Sprague-Dawley (SD) male rats were randomly assigned into three experimental groups. Each group consisted of eleven male rats including control group, HCD rats and hypercholesterolemic rats, which were treated with bLF (HCD+bLF). bLF was given by gavage (200 mg/kg/d). After 4 weeks of feeding and overnight fasting, total blood samples were collected. Results: The results showed the elevated level of Hcy, leptin, total cholesterol, low density lipoprotein cholesterol (LDL-C), ApoB and decrease in ApoA-I in non-treated HCD group compared to the control rats. Administration of bLF significantly ameliorated the Hcy and leptin levels with decrease in LDL-C and total cholesterol in rats fed with a high-cholesterol diet. bLF also tended to increase low serum concentration of ApoA-I and high density lipoprotein cholesterol (HDL-C) in HCD rats. Meanwhile, upon bLF-treated rats, there was a significant decrease in ApoB in HCD group. Conclusion: The findings indicated that bLF can improve the alteration of serum Hcy, leptin, apolipproteins and lipid changes in male rats fed with high-cholesterol diet. So, bLF can counteract with HCD elicited hyper-homocysteinemia and hyper-leptinemia, suggesting it to have the useful therapeutic potential in patients with atherosclerosis and lipid disorder.

Deep vein thrombosis and venous thromboembolism is a major health problem and one of the leading causes of maternal morbidity and mortality Recurrent pregnancy loss either early or late is a serious problem and has both psychological and physical impact. Thrombophilia are one of the most important causes of DVT as well as Recurrent pregnancy loss as it worsens the physiological hypercoagulable case which exists in pregnancy. Homocysteinemia is rare but an important cause of deep vein thrombosis and recurrent pregnancy loss. Serum homocysteine levels in pregnancy have been linked to preeclampsia,recurrent abortions and low birth weight. Diagnosis of this condition is missed on routine basis due to extremely less frequency of the evaluation of serum homocysteine levels on a routine basis. Here we report a case of hyperhomocysteinemia as underlying cause of bad obstetric history and DVT which are few of the classic presentations of the entity seen in the single patient. the condition was diagnosed by multidisciplinary approach. [ABSTRACT FROM AUTHOR]

Methylenetetrahydrofolate reductase (MTHFR) defi- ciency is an autosomal recessive disorder that results in hyperhomocysteinemia. Elevated homocysteine levels in the blood can cause arterial and venous thrombosis, atherosclerosis, recurrent pregnancy loss, and neurologic symptoms. Emerging research suggests links to other chronic illnesses as well. Anesthetic management of patients with MTHFR deficiency should focus on decreasing the risk of arterial or venous thrombosis and minimizing elevations in homocysteine levels. Thrombosis prevention includes the use of antiembolism compression stockings, intermittent pneumatic compression sleeves, subcutaneous heparin or low-molecular-weight heparin, early ambulation, and adequate hydration. Nitrous oxide is known to inhibit methionine synthase, a vitamin B12-dependent enzyme responsible for the breakdown of homocysteine, resulting in homocysteine elevation, and should be avoided in these patients. Intravenous vitamin B12 infusion before surgery may help decrease homocysteine levels; however, it is not readily available in most operating rooms. Propofol and sevoflurane do not increase homocysteine levels and are considered safe for patients with MTHFR deficiency. This case study describes a 58-year-old man with known MTHFR defi- ciency and his subsequent uneventful anesthetic care during a total knee replacement. [ABSTRACT FROM AUTHOR]

Intracranial aneurysms (IAs) are common lesions in the brain. There is a strong relation between hyperhomocysteinemia (HHcy) and cerebrovascular disease; we perform a retrospective study within the Chinese Han population to explore the association between HHcy and IAs. Two hundred six patients with IAs and 206 control subjects were evaluated for their serum total homocysteine levels. With multiple logistic regression analysis, the association between HHcy and the risk of IAs was estimated. Interaction and stratified analyses were conducted according to age, sex, BMI, smoking status, drinking status, and chronic disease histories. The threshold effect was examined by the two-piecewise linear regression model. The multivariate logistic regression analyses revealed a significant association between HHcy and IAs (odds ratio (OR) = 1.68; 95% confidence interval (CI), 1.02–2.75) after adjusting for classical vascular risk factors. And a 2% higher risk of IAs was observed, which was associated with a 1-μmol/L increase in serum total homocysteine level. The interaction analysis showed that age played an interactive role in the association between HHcy and IAs. In summary, our study provides evidence that HHcy is an independent risk factor for IAs in the Chinese Han population, especially in the elderly subgroup. Taking all the findings into consideration, longitudinal studies and clinical trials of homocysteine-lowering therapy via dietary or medical intervention are needed to assess the causal nature of these relationships. [ABSTRACT FROM AUTHOR]

Atypical hemolytic uremic syndrome (aHUS) is a rare, progressive, life-threating disease that frequently has a genetic component; it is usually caused by familial, sporadic or idiopathic reasons. We report a case of aHUS in a 21-month-old girl with coexisting of methylenetetrahydrofolate reductase mutations, homocysteinemia and thalassemia minor complicated by peripheral gangrene as extrarenal manifestation. [ABSTRACT FROM AUTHOR]

Objectives: To determine the frequency of elevated plasma homocysteine (Hcy) levels among type 2 diabetes mellitus (T2DM) patients. Study Design: Cross sectional study. Setting: Department of Medicine, Abbasi Shaheed Hospital, Karachi. Period: From 28 September 2012 to 26 March 2015. Material & Methods: Type 2 Diabetic patients fulfilling inclusion criteria were enrolled. Patients with conditions known to cause altered homocysteine levels were excluded. Patients' HbA1c and fasting serum homocysteine levels were obtained. Level >15 μmol/L was labeled as elevated. Data was collected with the help of Performa. Data was analyzed using SPSS version 21. Results: (90) ninety patients were enrolled in this study during study period with mean age of 61.5±7.3 years. Of (90) ninety patients, 45 (50%) were male and 45 (50%) were female with male to female ratio of 1:1. Mean duration of diabetes was 6.9±1.7 years. 40 (44.44%) cases were of controlled diabetes and 43 (47.7%) were on treatment. Of 90 patients 36 (40%) patients had Homocysteinemia. Homocysteine levels were found to be significantly raised in males 51.1% v/s 28.8% (p<0.03), older patients (>60 years of age) 55.5% v/s 16.6% (p<0.001), having diabetes for > 7 years, 59.2% v/s 17%(p<0.00004), in 21% v/s 57.4% cases who were and were not on treatment respectively (p<0.0004), in 22.5% patients with controlled diabetes and 54% patients with uncontrolled diabetes respectively (p<0.002). Conclusion: Hyperhomocystenemia is prevalent (40%) in type 2 diabetics with statistically significant raised levels in males, >60 years of age, non-compliant diabetics, have long duration diabetes, and uncontrolled disease. [ABSTRACT FROM AUTHOR]

La liste des anomalies à rechercher dans le cadre du bilan de thrombophilie n'a pas changé dans les dix dernières années, mais les évolutions technologiques et les résultats des travaux de recherche ont fait évoluer la place du génotypage dans le cadre du diagnostic des anomalies constitutionnelles des inhibiteurs de la coagulation, et tout particulièrement de l'antithrombine. Les travaux de recherche n'ont pas pour l'instant abouti à la mise en évidence de nouveaux marqueurs de risque susceptibles d'influencer les attitudes thérapeutiques. L'intérêt de l'évaluation des D-Dimères a été établi dans le cadre de scores de récidive. D'autres scores comportant plusieurs paramètres faiblement associés au risque sont en cours d'évaluation. Established biological thrombosis risk factors to be searched for in subjects with clinical thrombophilia are still, at the present time, the same as 10 years ago. No novel strong thrombosis risk factor has been identified in the past recent years. For coagulation inhibitors antithrombin, protein C and protein S, novel information on genotype-phenotype relationship lead to assign a larger place to genotyping for the diagnosis of inherited deficiency AT and deficiency in other inhibitors. There is also now a place for D-Dimer measurement in subjects with thrombophilia, a parameter which has been included in several scores evaluating risk of thrombosis recurrence. Other scores that include parameters tightly associated to thrombosis are currently being evaluated. [ABSTRACT FROM AUTHOR]

Acute ischemic stroke is rare in children, but it is one of the important causes of neurological morbidity. The etiology of AIS in childhood includes cardiac pathologies, cerebral arteriopathies, hypercoagulation, chemicals, drugs, inflammatory and autoimmune causes. In this article, we present an infant who has a genetic predisposition to hypercoagulation and comes with AIS clinic when multifactorial risk factors are added. The diagnosis, the underlying etiology, the risk factors affecting the process, the treatment of acute phase, the secondary treatment and the associated preventive approach on prognosis were discussed. [ABSTRACT FROM AUTHOR]

Homocysteinemia is a metabolic condition characterized by abnormally high level of homocysteine in the blood and is considered to be a risk factor for peripheral neuropathy. However, the cellular mechanisms underlying toxic effects of homocysteine on the processing of peripheral nociception have not yet been investigated comprehensively. Here, using a rodent model of experimental homocysteinemia, we report the causal association between homocysteine and the development of mechanical allodynia. Homocysteinemia-induced mechanical allodynia was reversed on pharmacological inhibition of T-type calcium channels. In addition, our in vitro studies indicate that homocysteine enhances recombinant T-type calcium currents by promoting the recycling of Cav3.2 channels back to the plasma membrane through a protein kinase C-dependent signaling pathway that requires the direct phosphorylation of Cav3.2 at specific loci. Altogether, these results reveal an unrecognized signaling pathway that modulates the expression of T-type calcium channels, and may potentially contribute to the development of peripheral neuropathy associated with homocysteinemia. [ABSTRACT FROM AUTHOR]

Combined homocysteinemia with methylmalonic aciduria (MMA/HCY) are genetic disorders of intracellular cobalamin (cbl) transport and processing that cause downstream deficiencies in methylcobalamin and adenosylcobalamin. Untreated disease is characterized biochemically by methylmalonic aciduria and hyperhomocysteinemia, while the clinical features are variable. When spastic paraplegia (SP) dominates, it is difficult to differentiate from hereditary spastic paraplegia (HSP). Clinical, biochemical and imaging features were reviewed in eight patients with MMA/HCY that mimicked HSP. Seven males and one female were enrolled. The median onset age was 13 years old (range 7–26 years old). The median time delay of diagnosis was 20.5 months (range 2–60 months). Spastic gait was the first symptom in four patients, while the other four patients presented with chronic emotional abnormalities or cognitive impairment. The main clinical manifestation was SP, and other neurological symptoms included cognitive impairment (5/8), spastic dysuria (3/8), personality change and depression (3/8), ataxia (2/8), seizures (2/8), limb numbness (2/8), and developmental delay (2/8). When patients were diagnosed, the mean serum homocysteine level, the methylmalonic acid level in urine, the serum propionylcarnitine (C3) level and the ratios of C3-to-acetylcarnitine (C2) and free carnitine (C0) were all dramatically elevated. Cranial MRIs showed nothing remarkable except mild brain atrophy. All spinal MRIs were normal except for case 8. Definite compound heterozygous mutations in MMACHC were detected in five cases. Follow-up indicated partial improvement in all the patients after intramuscular cbl, oral betaine and folate, supporting the diagnosis of MMA/HCY. Our data highlight the need for extensive investigation of intracellular cbl transport and processing, when spastic paraparesis is a prominent component of the clinical picture. Testing for urine methylmalonic acid and serum homocysteine levels is a simple but critical approach in suspected cases. Genetic testing, especially for MMACHC gene mutations, is needed. Raising awareness of this disorder could result in the timely initiation of targeted treatment, which may significantly improve patient outcomes. [ABSTRACT FROM AUTHOR]

Les folates et cobalamines sont des cofacteurs nécessaires à la synthèse de l'ADN via des réactions de transfert d'unités monocarbonées. Les conséquences d'une carence en l'une ou l'autre de ces vitamines portent d'abord sur les processus tissulaires à haut niveau de renouvellement, au premier rang desquels l'hématopoïèse et les tissus muqueux. L'atteinte hématologique est variable, de la classique « anémie mégaloblastique » à des formes moins expressives telles que des thrombopénies isolées. Mais le diagnostic doit également être évoqué devant des manifestations extrahématologiques qui dépendent de fonctions métaboliques propres à chacune de ces vitamines. Ainsi, la vitamine B12 est impliquée dans la synthèse de la myéline, et les carences peuvent induire des manifestations neuropsychiatriques parfois irréversibles. Les carences en folates chez la femme enceinte ont, elles, été associées à des défauts de fermeture du tube neural, et une supplémentation systématique dès la phase de conception est recommandée. Le diagnostic de routine est basé sur les dosages immunologiques des folates et de la vitamine B12 sériques dont l'interprétation doit toujours tenir compte du tableau clinique car ils manquent de spécificité et parfois de sensibilité. Dans des situations diagnostiques difficiles, des tests complémentaires tels que le dosage de l'homocystéine dans ces deux carences, de l'holo-transcobalamine et de l'acide méthyl-malonique dans les carences en B12, ou des folates érythrocytaires dans les carences en folates peuvent être proposés. Folates and cobalamins are cofactors both involved in DNA synthesis through one carbon metabolism. Any deficiency in one of these vitamins will impact tissues with a high mitotic index, particularly mucosa and hematopoiesis, leading to the classical glossitis and megaloblastic anemia. However, hematological impairment may be more discreet and difficult to recognize, restricted to macrocytosis or isolated thrombocytopenia. Of note, deficiency may lead to extra hematological features that depend on specific metabolic functions of each vitamin. Cobalamins are involved in myelin synthesis and deficiency may lead to sometimes irreversible neuropsychiatric complications. Folates deficiency in pregnant women has been associated with neural tube defects and peri-conception folic acid supplementation is now recommended. Routine biological diagnosis is based on serum folates and vitamin B12 immuno-assays that should be interpreted carefully and confronted with clinical data. In difficult cases, other tests with a higher sensitivity and/or specificity such as homocysteine, methylmalonic acid, holotranscobalamin and red blood cell folates level can be used. [ABSTRACT FROM AUTHOR]

Résumé Contexte Les caractéristiques lésionnelles coronaires ainsi que la thrombogénicité du patient peuvent expliquer la survenue d'événements coronariens. Chez les sujets jeunes, les conditions locales sont habituellement moindres et la thrombogénicité pourrait jouer un rôle plus significatif. La réalisation d'un bilan de thrombophilie se justifierait chez les sujets les plus jeunes et pourrait conduire à modifier la prise en charge thérapeutique. Objectif Évaluer la prévalence de la thrombophilie et les modifications thérapeutiques chez les adultes d'âge ≤ 55 ans admis pour un syndrome coronarien aigu avec sus-décalage du segment ST (SCA ST+). Méthodes De janvier 2013 à janvier 2017, les données de tous les patients d'âge ≤ 55 ans avec un SCA ST+ admis en urgence ont été rétrospectivement extraites de notre base de données. Un bilan de thrombophilie avait été réalisé selon l'orientation clinique (présence ou non de facteurs de risque cardiovasculaire [FRCV]), biologique et/ou angiographique. Résultats Un total de 133 patients ≤ 55 ans avec un SCA ST+ ont été inclus. Un arrêt cardiaque est survenu chez 15 patients (11 %). Aucun ou un seul FRCV était noté chez 47 patients (35 %). Un tabagisme actif était retrouvé chez 93 patients (70 %), une addiction aux drogues (cannabis, cocaïne) chez 19 patients (14 %). Un sous-groupe de 51 patients (38 %) a bénéficié d'un bilan de thrombophilie. Les patients avec un bilan de thrombophilie étaient plus jeunes, moins souvent tabagiques et présentaient moins de FRCV que les patients sans investigation (p < 0,001). Une maladie mono-tronculaire était retrouvée chez 88 patients (66 %). Il n'y avait pas de différence entre les 2 groupes concernant les caractéristiques angiographiques. L'étiologie la plus fréquemment retenue, retrouvée chez 122 patients (92 %), était une thrombose intra-artérielle de novo en rapport avec une maladie athérosclérotique. Chez les patients ayant bénéficié d'un bilan de thrombophilie (n = 51), les résultats biologiques ont montré au moins une anomalie chez 22 patients (43 %) et un ajustement de la thérapeutique a été fait chez 6 patients (12 %). Conclusion La recherche d'un facteur de thrombophilie chez les jeunes adultes avec SCA ST+ permet de mettre en évidence une anomalie dans 43 % des cas. Sa mise en évidence peut amener à modifier le traitement antithrombotique. Abstract Background Coronary lesions characteristics as well as patient thrombogenicity can explain coronary events manifestation. In young patient, local conditions are usually less important and thrombogenicity could play a significant role. Assessing thrombophilia could be justified in young patients and may induce an adapted therapeutic management. Purpose We aimed to assess the prevalence of thrombophilia and therapeutic modification in young adults aged ≤ 55 years admitted in our department for ST elevation myocardial infarction (STEMI). Methods From January 2013 to January 2017, data on all patients aged ≤ 55 years with STEMI admitted in emergency were retrospectively retrieved from our database. Thrombophilia investigation was made regarding clinical (with or without cardiovascular risk factors [CVRF]), biological and/or angiographic evaluation. Results A total of 133 patients aged ≤ 55 years with STEMI were included. Cardiac arrest occurred in 15 patients (11%). One or less CVRF were found in 47 patients (35%). Smoking was reported in 93 patients (70%) and drug addiction (cannabis, cocaine) in 19 patients (14%). A subset of 51 patients (38%) were screened for thrombophilia. Patients with thrombophilia assessment were younger, less active smokers and presented less CVRF than patients without investigation (P < 0.001). Single vessel diseased was found in 88 patients (66%). No differences regarding coronary procedural characteristic were found between the two groups. The most frequently encountered aetiology, found in 122 patients (92%), was de novo intra-arterial thrombosis related to atherosclerosis. In patients with thrombophilia assessment (n = 51), one or more abnormal biological results was found in 22 patients (43%) and a therapeutic adjustment was made in 6 patients (12%). Conclusion Thrombophilia screening in young STEMI adults showed an abnormality in 43% of cases. Antithrombotic treatment can be modified after its demonstration. [ABSTRACT FROM AUTHOR]

Chronic Obstructive Pulmonary Disease(COPD) is well-known with the high rate of incidence and mortality worldwide, which leads significant burden, disordered individual's or families' quality of life in a certain degree. Homocysteinemia damages the whole organ system, with the deepening of the research, researchers pay more attention to hcy-related pulmonary diseases. Some scientist puts forward that Hcy maybe a meanningful factor during the pathogenesis of COPD. Part study finds that the plasmof Homocysteinemia in patients with copd is in a high level, even is related to COPD severity. Hcy can produce a large number of ROS and free ions, lead endothelial stress, which is regulated by the oxidation of Hcy, also can reduce content of glutathione in the lungs. This article will discuss the metabolic pathways and stress-responest of Hcy in the development of COPD, which all happens to damage the lung. The author also sorts out the latest treatment. [ABSTRACT FROM AUTHOR]

Sugar production is a significant worldwide agro-based industry generally produced by extraction mostly from sugar plants, principally Beta vulgaris var. saccharifera and sugarcane Saccharum officinarum L. Other plant resources for sucrose include grape, mulberry, apricot, prune, fig, apple, and carob. During sucrose production, molasses is typically recovered as a side product and exceeds 50 million tons, posing it as a potential human food source. Molasses is an essential source of monosaccharides (glucose, fructose, galactose, arabinose, xylose), disaccharides (sucrose), and trisaccharides (raffinose). It is also rich in vitamins, betaine, and minerals such as potassium and calcium, meditating for several health benefits and treating ailments such as hyperhomocysteinemia, reproductive functions, pediatric constipation, ulcerative colitis, and immune modulation. In addition to these health benefits, molasses has improved food palatability and sensory attributes, lessening sucrose consumption and providing a better nutritional profile in processed foods. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Lipid metabolism disorder or hyperlipidemia is known as a risk factor for cardiovascular disease, the increase in serum homocysteine and leptin are associated with atherosclerotic disease. The purpose of the present study was to examine the effects of bovine lactoferrin (bLF) on serum homocysteine (Hcy), apolipoproteinA-I (ApoA-I) and B (ApoB), leptin and lipid profile changes in high-cholesterol-diet (HCD) fed rats. Methods: The Healthy Adult Sprague-Dawley (SD) male rats were randomly assigned into three experimental groups. Each group consisted of eleven male rats including control group, HCD rats and hypercholesterolemic rats, which were treated with bLF (HCD+bLF). bLF was given by gavage (200 mg/kg/d). After 4 weeks of feeding and overnight fasting, total blood samples were collected. Results: The results showed the elevated level of Hcy, leptin, total cholesterol, low density lipoprotein cholesterol (LDL-C), ApoB and decrease in ApoA-I in non-treated HCD group compared to the control rats. Administration of bLF significantly ameliorated the Hcy and leptin levels with decrease in LDL-C and total cholesterol in rats fed with a high-cholesterol diet. bLF also tended to increase low serum concentration of ApoA-I and high density lipoprotein cholesterol (HDL-C) in HCD rats. Meanwhile, upon bLF-treated rats, there was a significant decrease in ApoB in HCD group. Conclusion: The findings indicated that bLF can improve the alteration of serum Hcy, leptin, apolipproteins and lipid changes in male rats fed with high-cholesterol diet. So, bLF can counteract with HCD elicited hyper-homocysteinemia and hyper-leptinemia, suggesting it to have the useful therapeutic potential in patients with atherosclerosis and lipid disorder. [ABSTRACT FROM AUTHOR]

• Vitamin B 12 deficiency is prevalent in the elderly and has been reported to be associated with ischemic stroke. • The mechanisms maybe include the disorder of methylation metabolism and accumulation of toxic metabolites (homocysteine and methylmalonic acid), immune dysfunction, induce oxidative stress and endoplasmic reticulum stress, affect gut microbial composition and gut-brain immune homeostasis and toxic stress responses to the brain. • Vitamin B 12 deficiency will lead to cerebral artery atherosclerosis, changes in myelination, influence the metabolism and transmission between nerve tissue, and ultimately cause the occurrence and development of ischemic stroke. • Vitamin B 12 supplementation can reduce the incidence of stroke, delay the progression and improve the prognosis of stroke. Ischemic stroke is the most prevalent form of stroke and has a high incidence in older adults, characterized by high morbidity, mortality, disability, and recurrence rate. Vitamin B 12 deficiency is prevalent in the elderly and has been reported to be associated with ischemic stroke. The mechanisms maybe include the disorder of methylation metabolism, accumulation of toxic metabolites, immune dysfunction, affecting gut microbial composition and gut-brain immune homeostasis, and toxic stress responses to the brain. Vitamin B 12 deficiency may lead to cerebral artery atherosclerosis, change myelination, influence the metabolism and transmission between nerve tissue, and ultimately causes the occurrence and development of ischemic stroke. This paper reviews the correlation between vitamin B 12 deficiency and ischemic stroke, looking forward to improving clinicians' understanding and providing new therapeutic directions for ischemic stroke. [ABSTRACT FROM AUTHOR]

Autistic spectrum disorder (ASD) is a developmental disability of the central nervous system with rapid worsening. A subset of patients also has mitochondrial dysfunction leading to increased sensitivity to various anesthetic agents. Rarely, gene mutation in these patients results in homocysteinemia which causes higher incidences of thromboembolism, hypoglycemia, and seizures. Anesthetic management of ASD with homocysteinemia and refractory seizures has not been previously reported.

Combined methylmalonic acidemia (MMA) and homocysteinemia are a group of autosomal recessive disorders caused by inborn errors of cobalamin metabolism, including CblC, D, F, and J, with cblC being the most common subtype. The clinical manifestations of combined MMA and homocysteinemia vary, but typically include neurologic, developmental and hematologic abnormalities.We report 4 children with combined MMA and homocysteinemia who presented predominantly with late-onset diffuse lung diseases (DLD). Of these, 3 accompanied by pulmonary arterial hypertension (PAH), 1 accompanied by hypertension, and 2 accompanied by renal thrombotic microangiopathy (TMA), which was confirmed by renal biopsy. This confirms combined MMA and homocysteinemia should be considered in the differential diagnosis of DLD with or without PAH or renal TMA. [ABSTRACT FROM AUTHOR]

The most common cause of isolated inherited homocysteinemia is a deficiency of the enzyme cystathionine β-synthase (CBS). Clinical manifestations of CBS deficiency can include ectopia lentis, thromboembolism, marfanoid habits, and intellectual disability. CBS deficiency, which affects the transsulfuration pathway, is marked biochemically by elevated serum homocysteine and plasma methionine. We report a patient with homocysteinemia, low plasma methionine, and no significant neurological abnormalities who presented with bilateral subluxated crystalline lenses due to a 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency. MTHFR deficiency, a disorder in the remethylation pathway, can cause mild to severe disease, although most presentations include neurological involvement. MTHFR deficiency has not been previously associated with lens subluxation or complete dislocation. Prolonged exposure to elevated serum homocysteine levels is most likely the explanation for her ectopia lentis. This case expands the differential diagnosis of homocysteinemia and highlights the need for a correct diagnosis to optimize the clinical outcome of patients with this condition. [ABSTRACT FROM PUBLISHER]