Higher Homocysteine Levels Research Articles

Study of homocysteine and its correlation with biochemical parameters in patients with chronic renal failure

Homocysteine is an amino acid produced when proteins are broken down. A high homocysteine level, also called hyperhomocysteinemia, can contribute to arterial damage and blood clots in your blood vessels. Hyperhomocysteinemia (Hhcy) occurs in chronic kidney disease (CKD) patients because of impaired renal metabolism and reduced renal excretion Chronic renal failure is a condition involving a decrease in the kidneys' ability to filter waste and fluid from the blood. It is chronic, meaning that the condition develops over a long period of time and is not reversible. The condition is also commonly known as chronic kidney disease (CKD). The aim of the study is to measure homocysteine levels for patients with chronic renal failure before dialysis and to find the relationship between homocysteine and biochemical parameters such as B12, folic acid, ferritin and albumin. Study Design: Blood samples were obtained from (130) men and women. It was divided into (68) hemodialysis patients, aged from (20-80) years and (62) control, aged from (20-80) years, and they were campared.

Assessment of role of homocysteine in coronary heart disease

Background: Homocysteine has been under a lot of speculation since its discovery in 1932. The present study was conducted to assess the role of homocysteine in coronary heart disease. Materials and Methods: 76 patients of coronary heart disease of both genders were included. The body mass index was calculated as weight (kg)/height (m)2. Blood pressures were measured. Serum total homocysteine was measured. Serum total and HDL cholesterol were determined with standard methods. Serum creatinine was determined with a modified Jaffe´ method. Results: Out of 76 patients, males were 52 and females were 24. The mean BMI (Kg/m2) was 25.4, SBP (mm Hg) was 154.2, DBP (mm Hg) was 86.4, serum cholesterol (mmol/L) was 6.52, serum HDL (mmol/L) was 1.08, serum creatinine (µmmol/L) was 112.9. Co-morbidities comprise of hypertension in 34, diabetes mellitus in 8, myocardial infarction in 14, stroke in 7 and smoking in 26. The difference was significant (P< 0.05). Crude value was 1.09 and adjusted value was 1.56 in CHD and crude value was 1.88, adjusted value was 1.27, normotensive adjusted value was 6.17 and hypertensive adjusted value was 1.64. Conclusion: A high homocysteine level is common and is strongly associated with the prevalence of coronary heart disease and cerebrovascular disease.

The determinants of collateral circulation status in patients with chronic cerebral arterial circle occlusion: A STROBE Study.

The condition of collateral pathways is an important predictor of stroke prognoses; however the major determinants of collaterals are still unknown. The purpose of this study is to identify potentially determinants for collateral circulation status in patients with chronic occlusion of cerebral arterial circle.All patients with chronic occlusion of either unilateral internal carotid artery or middle cerebral artery M1 or M2 segment, diagnosed by digital subtraction angiography at the neurology department of the First Medical Centre of Chinese PLA General Hospital from January 2015 to December 2017, were retrospectively collected in our sample. After screening according to inclusion and exclusion criteria, the patients’ relevant clinical data were collected and analyzed. Collateral circulations were assessed by 2 independent raters using the American society of interventional and therapeutic neuroradiology/society of interventional radiology flow-grading system.Baseline characteristics (n = 163): our sample consists of 116 (71.2%) male and 47 (28.8%) female patients with an average age of 57.5 ± 11.9 years. Cerebral collateral flow was poor in 59 (36.2%) patients. Our univariate analyses showed that poor collateral circulation was associated with lower high-density lipoproteins cholesterol (HDL), elevated homocysteine levels, aging and hyperlipidemia. A multivariate analysis identified HDL, homocysteine levels and ageing as major predictors for collateral circulation status. In the subgroup analysis, the HDL contributed to collateral angiogenesis internal carotid artery occlusion group. In the middle cerebral artery occlusion group, the homocysteine and ageing were related to the poor collateral status.Low HDL, high levels of homocysteine and ageing are identified as possible risk factors for a poor collateral vessel blood flow in patients with chronic anterior circulation occlusion.

VITAMIN B 12 AND HOMOCYSTEINE LEVELS IN PRIMI GRAVIDA PATIENTS WITH PRE-ECLAMPSIA: AN EXPERIENCE FROM A TERTIARY CARE HOSPITAL OF PAKISTAN

Objective: To determine the frequency of serum vitamin B12 and homocysteine levels in patients with Pre-ec­lampsia. Methodology: This cross-sectional study was carried out in Department of Gynecology and Obstetrics, Lady Read­ing Hospital, Peshawar in collaboration with the Department of Biochemistry of Khyber Medical University (KMU), from May 2019 to December 2019 after obtaining ethical approval from Advanced Study and Research Board (ASRB). Using non-probability convenient sample technique, 60 patients who were Primi Gravida with Pre-eclamp­sia were admitted via OPD or labour room. Data was collected from hospital record , charts and documented and analyzed in SPSS version 22. Results: The mean age of the patients in this study was 21.75 ± 2.05 years. The mean vitamin B 12 levels recorded in our study was 175 ± 34.39 pmol/l. Vitamin B 12 levels in most of the participants, 45(75%) were in normal ranges. 12(20%) patients were deficient in vitamin B 12 levels while 03(05%) patients had high levels of vitamin B12. The mean serum Homocysteine level in our study was 9.63 ± 3.46 umol/l. Most of the participants 48 (80%) had normal levels while 09(15%) patients had high levels of serum Homocysteine while only 03 (05%) patients were deficient in serum Homocysteine levels. Conclusion: Majority of the patients with Pre eclampsia had normal levels of Homocysteine and vitamin B12. There was an inverse correlation between serum Vitamin B12 and Homocysteine levels in Pre-eclamptic patients

Association of pentosidine and homocysteine levels with number of teeth present in Japanese postmenopausal women.

Little is known about whether substances inducing tissue protein degeneration in the oral cavity are associated with the number of teeth present in postmenopausal women. We sought to investigate the association of urinary pentosidine and serum homocysteine levels with the number of teeth and subsequent tooth loss in Japanese postmenopausal women. Among participants in the Nagano Cohort Study, 785 postmenopausal women (mean age, 68.1years) participated in the present study. The number of teeth was re-counted at the time of follow-up in 610 women. Poisson regression analysis was used to investigate differences in the number of teeth among quartiles of pentosidine or homocysteine, adjusting for covariates that correlated with the number of teeth. A Cox proportional hazard model was used to evaluate the association of subsequent tooth loss with pentosidine or homocysteine levels. Pentosidine quartiles were not associated with the number of teeth at baseline. Participants in the highest homocysteine quartile had significantly fewer teeth at baseline than those in the third and lowest quartiles (p < 0.001 for both). Those in the second quartile had fewer teeth than those in the third (p = 0.001) and lowest (p < 0.001) quartiles. An increased risk of tooth loss during follow-up was significantly associated with higher urinary pentosidine (hazard ratio = 1.073 for 10pmol/mgCre; p = 0.001). Postmenopausal women with higher homocysteine levels had fewer teeth at baseline. A higher pentosidine concentration increased the risk of subsequent tooth loss. High pentosidine or homocysteine concentrations may be associated with tooth loss in postmenopausal women.

SYNERGISTIC EFFECT OF HIGH HOMOCYSTEINE AND LOW VITAMIN B12 LEVELS ON CARDIOVASCULAR AND STROKE RISK OF HYPERTENSIVE PATIENTS

Objective: Arterial hypertension is a risk factor for cardiovascular (CV) events, including stroke. High blood homocysteine levels (hyperhomocysteinemia) are also considered to increase CV risk and are associated with vitamin B12 deficiency that possibly increase CV and stroke risk, as well. The present study assessed the possible relation of high homocysteine and low vitamin B12 levels with the underlying CV and stroke risk of hypertensive patients. Design and method: This retrospective study comprised all hypertensives referred to our institutions and had a blood sample measurement of homocysteine and B12 (n = 32800). The 10-year fatal CV risk and stroke risk were calculated with the HeartScore and the FraminghamStrokeScore, respectively. The population was divided in quartiles according to homocysteine levels (groups 1, 2, 3 and 4 for increasing levels) and B12 levels (groups 1, 2, 3 and 4 for decreasing levels). Cardiovascular and stroke risk were calculated for each homocysteine and B12 quartile group as well as for each of the 16 homocysteine/B12 combination quartile subgroups. Results: The mean values for homocysteine were 13.3 ± 7.2 μmol/l and for B12 525 ± 196 pg/ml. For homocysteine quartiles 1, 2, 3, 4, CV risk was 3.4%, 5.5%, 9.0%, 17.9%, respectively (pfor trend 0.05). For B12 quartiles 1, 2, 3, 4, CV risk was 3.0%, 6.2%, 9.5%, 15.1%, respectively (pfor trend 0.01). Correlation coefficient ® between homocysteine and CV risk values was 0.416 (p &lt; 0.0001) while between B12 and CV risk values was -0.369 (p &lt; 0.0001). For homocysteine quartiles 1, 2, 3, 4, stroke risk was 4.2%, 7.3%, 12.9%, 25.0%, respectively (pfor trend 0.04). For B12 quartiles 1, 2, 3, 4, stroke risk was 5.4%, 9.2%, 13.4%, 19.3%, respectively (pfor trend 0.08). Correlation coefficient ® between homocysteine and stroke risk values was 0.474 (p &lt; 0.0001) while between B12 and stroke risk values was -0.348 (p &lt; 0.0001). The synergistic effect of increasing homocysteine and decreasing B12 values on CV and stroke risk increase is presented in Figure. Conclusions: High homocysteine levels and low vitamin B12 levels are individually and synergistically associated with the underlying CV and stroke risk of hypertensive individuals. Possible mechanisms merit further examination.

SYNERGISTIC EFFECT OF HIGH HOMOCYSTEINE AND LOW VITAMIN B12 LEVELS ON THE PREVALENCE OF ATRIAL FIBRILLATION IN HYPERTENSIVE PATIENTS

Objective: Atrial fibrillation (AF) is common arrhythmia in hypertensive patients. Besides hypertension, several other conditions are deemed to be associated with AF. High blood homocysteine levels (hyperhomocysteinemia) is a known risk factor for cardiovascular disease and are associated with vitamin B12 deficiency that possibly increase cardiovascular risk, as well. The present study assessed the possible effect of high homocysteine and low B12 levels on AF prevalence in hypertensive patients. Design and method: This retrospective study comprised all hypertensives referred to our institutions and had a blood sample measurement of homocysteine and B12 (n = 32800). The presence of sustained AF (SAF; Long-standing/Persistent or Permanent AF) was recorded with a resting electrocardiogram (ECG). Paroxysms of AF (PAF) were confirmed with previous relevant ECGs provided by the patient. The population was divided in quartiles according to homocysteine levels (groups 1, 2, 3 and 4 for increasing levels) and B12 levels (groups 1, 2, 3 and 4 for decreasing levels). The prevalence of AF (SAF and PAF) was calculated for each homocysteine and B12 quartile group as well as for each of the 16 homocysteine/B12 combination quartile subgroups. Results: The mean values for homocysteine were 13.3 ± 7.2 ?mol/l and for B12 525 ± 196 pg/ml. The prevalence of SAF, PAF and all-type AF (SAF and PAF) was 5.0%, 6.1% and 11.1%, respectively. For homocysteine quartiles 1, 2, 3, 4, SAF prevalence was 2.9%, 5.3%, 11.7%, 24.3% (pfor trend 0.049), PAF prevalence was 0.6%, 0.9%, 4.6%, 14.0% (pfor trend 0.090) and all-type AF prevalence was 3.2%, 5.4%, 11.5%, 22.2% (pfor trend 0.051), respectively. For B12 quartiles 1, 2, 3, 4, SAF prevalence was 2.9%, 6.4%, 11.0%, 20.2% (pfor trend 0.030), PAF prevalence was 2.5%, 5.1%, 7.7%, 9.0% (pfor trend 0.009) and all type-AF prevalence was 2.4%, 7.1%, 16.8% 21.0% (pfor trend 0.019), respectively. The synergistic effect of increasing homocysteine and decreasing B12 values on SAF, PAF and all-type AF prevalence is presented in Figure. Conclusions: High homocysteine levels and low vitamin B12 levels are individually and synergistically associated with the prevalence of AF in hypertensive individuals. Underlying mechanisms merit further examination.

The Role of Dietary Sulfur-Containing Antioxidants on the Reducing Effects of Lifestyle Modification Program on the NAFLD-Associated CVDs

ObjectivesNon-Alcoholic Fatty Liver Disease (NAFLD) is a silent disease linked to behavioral habits (poor diet and sedentary lifestyle) with inflammatory and oxidative stresses as background, leading to cardiovascular diseases (CVDs) as the worse outcome. These point out to lifestyle modification program(LSMP) as a potential non-pharmacological strategy in modulation NAFLD and CVDs risks. Purpose: To evaluate the LSMP on sulfur-containing markers in the NAFLD- high-risk CVDs course. MethodsIntervention study with 170 subjects with algorithm-diagnosed NAFLD(Fatty Liver Index ≥ 60) undergoing a 10 wks of the LSMP with daily supervised mixed physical exercise and nutritional counseling. Participants, adults (>35 yrs) had data collected before and after 10 wks for variables: demographic, socioeconomic, dietary, anthropometric and plasma biochemistry (inflammatory-oxidative and sulfur-containing markers). CVDs risk was indicated by higher risk of both Plasma Atherogenic Index (PAI) and Coronary Artery Disease (CAD). Statistical analyzes were performed for p = 0.05. ResultsThe sample of 73% women and 51.8% under 60 yrs old presented 37.6% low-physical activity level (PAL) and 95.3% poor-quality diet. At baseline the 30% NAFLD patients presented 13.5% high risk of PAI and 11.2% high-risk CAD along with 90% low PAL and 100% poor-quality diet. Inadequate-food ingestion was detected in protein, lipid, fiber, methionine (Met), Phosphatidylcholine (Pho), choline (Cho) and betaine (Bet). Their plasma profile showed higher inflammatory (us-CRP) and oxidative stress (MDA and GSSG) with lower antioxidant status (GSH) along with higher levels of homocysteine (Hcy) and Trimetylamine N-oxide (TMAO). The 10-wk LSMP improved VO2max (20%) and protein, lipid, fiber, Met, Pho, Cho and Bet intake. There was a reduction of 27% in NAFLD as well as in those with higher-PAI (46.2%) and higher-CAD (45%) associated with improvements in plasma Met, Pho, Cho and Bet, as well in Hcy, and TMAO. ConclusionsBy improving sulfur-containing anti-oxidants and aerobic conditioning (anti-inflammatory effect) the present LSMP was effective in reducing the NAFLD recrudescence to CVDs. Funding SourcesCAPES and CNPq

Investıgatıon of The Effect of Serum Homocysteıne Level on Cognıtıve Functıons in Multıple Sclerosıs Patıents

Objective: In this study, we aimed to investigate whether serum homocysteine level was higher in patients with MS, and evaluate the effect of this situation on cognitive functions. In addition, we aimed to determine whether high blood homocysteine level is associated with socio-demographic and clinical features and determine the affected cognitive functions with neuropsychological tests.Methods: We looked at changes in the levels of vitamin B12 and folic acid associated with high levels of serum homocysteine levels. Cognitive performance, and laboratory values of 60 cases with Relapsing-remitting MS (RRMS) patient, and 30 healthy volunteers were compared. The frontal lobe activities, information processing speed, flexibility, and the ability of the calculation, as well as cognitive functions of attention and visuospatial perception and construction of complex skills were also evaluated. For these purposes, Paced Auditory Serial Addition Test (PASAT), Line Orientation Test (LOT) and Stroop Test were used.Results: Test performance for all of the test steps were found to be defective in MS group more than the control group subjects. In addition, all steps of the test performance were found to be impaired in both patients and healthy subjects with high levels of homocysteine(p&amp;lt;0.001).Conclusion: In this study visual memory processes, visual-spatial functions, construction skills, planning, programming and executive functions were found to be significantly deteriorated and the reaction time prolonged in RRMS patients with high levels of homocysteine compared with healthy control group

Serum Homocysteine Level Predictive Capability for Severity of Restenosis Post Percutaneous Coronary Intervention

Background: In stent restenosis (ISR) is one of the major complications after stent implantation. Thus, there is a growing interest in identifying a biomarker for the onset of ISR. High levels of serum homocysteine (Hcy) have been associated with the progression of cardiovascular disease. Therefore, the study was carried out to quantify the correlation between serum Hcy and ISR severity. Compared with coronary angiography (CAG), Hcy levels provided a significantly better clinical detection of ISR severity after PCI. Methods: A total of 155 patients were recruited from Shanxi Bethune hospital, from 6 months to 2 years post PCI. Serum Hcy levels and postoperative angiography results were used to differentiate the patients into two experimental groups: ISR (>50% diametrical stenosis), and non-ISR. The non-ISR included two subgroups: intimal hyperplasia (10–50% diametrical stenosis), and recovery (<10% diametrical stenosis). In addition, a group of 80 healthy individuals was used as a negative control. The correlation between homocysteine level and ISR severity t was analyzed for all groups. In addition, the correlation between serum Hcy level and the severity of ISR in the experimental group was analyzed by the Pearson correlation test. Results: The serum Hcy level in the experimental group and control group was determined to be (20.21 ± 11.42) μmol/L and (15.11 ± 10.25) μmol/L respectively. The level of serum Hcy in the experimental group was significantly higher than in the control group (t-value of 2.385; p-value of 0.019). The serum Hcy level in the restenosis and the intimal hyperplasia group was (25.72 ± 13.71) μmol/L and (17.35 ± 7.70) μmol/L respectively. The serum Hcy level in the restenosis group was significantly higher than in the intimal hyperplasia group (t-value of 2.215; p-value of 0.033). The level of serum Hcy in the group without a plaque in the stent was (16.30 ± 6.08) μmol/L, whereas in the control group was (15.11 ± 10.25) μmol/L. The no plaque group had a slightly higher serum Hcy level than the control group (t-value of 0.634; p-value of 0.528). All included patients were divided into four quartiles based on the serum Hcy concentration: quartile 1 (8.90–13.20 μmol/L), quartile 2 (13.30–16.45 μmol/L), quartile 3 (16.60–24.25 μmol/L) and quartile 4 (24.30-65.30 μ mol/L). The incidence of ISR was 5, 6.25, 7.5 and 15%, in the 1,2,3 and four quartiles respectively. The serum Hcy level in the experimental group was (20.21 ± 11.42) μmol/L, the severity of in-stent restenosis was (0.25 ± 0.31), (R-value was 0.234; p-value was 0.037), indicating a correlation between serum Hcy and the severity of restenosis (p < 0.05). Taking coronary angiography as the gold standard, a ROC curve analysis was performed on the serum Hcy levels for the experimental group. The area under the curve (AUC) was 0.718 (95% CI 0.585-0.854, p < 0.001), indicating that the serum Hcy concentration could predict ISR. On the ROC curve, the best critical value of serum Hcy concentration for predicting ISR was 20.05 μmol/L, with a sensitivity of 45% and specificity of 88.1%. Conclusion: A positive correlation was observed between homocysteine and the severity of restenosis after PCI, The level of Hcy could serve as a predictive biomarker for the severity of ISR.

Hyperhomocysteinemia Increases Cortical Excitability and Aggravates Mechanical Hyperalgesia and Anxiety in a Nitroglycerine-Induced Migraine Model in Rats.

Homocysteine is a sulfur-containing endogenous amino acid leading to neurotoxic effects at high concentrations. Population studies suggest an association between plasma homocysteine levels and the risk of migraine headaches. The aim of this study was to analyze the sensitivity of rats with prenatal hyperhomocysteinemia (hHCY) in respect of the development of behavioral correlates of headache and spreading cortical depolarization (CSD) in a migraine model induced by the administration of the nitric oxide (NO) donor nitroglycerin. Animals with hHCY were characterized by migraine-related symptoms such as mechanical hyperalgesia, high-level anxiety, photophobia, as well as an enhanced level of neuronal activity in the somatosensory cortex along with a lower threshold of CSD generation. Likewise, acute or chronic intermittent administration of nitroglycerin also induced the development of mechanical allodynia, photophobia and anxiety in control groups. However, these symptoms were more pronounced in rats with hHCY. Unlike hHCY, nitroglycerin administration did not affect the threshold of CSD generation, but like hHCY, increased the background neuronal activity in layers 2/3 and 4 of the cerebral cortex. The latter was more pronounced in animals with hHCY. Thus, the migraine profile associated with hHCY can be further exaggerated in conditions with enhanced levels of migraine triggering the gaseous transmitter NO. Our data are consistent with the view that high levels of plasma homocysteine can act as a risk factor for the development of migraine.

Relationship of lung function with homocysteine, vitamin B12 and folic acid level in metabolic syndrome

Background: Metabolic syndrome (MetS) is a complex metabolic disorder and with debilitating effects on many organs including lung function impairment. Hyperhomocysteinaemia is caused by nutritional deficiency of vitamin B12 and folic acid can increase this risk further. Both the metabolic syndrome and hyperhomocysteinaemia adversely affect the lung function. But no study was found in Bangladeshi MetS in this regard. Objective: To assess the relationship of lung function with serum homocysteine, vitamin B12 and folic acid level in metabolic syndrome. Methods: This cross-sectional study was conducted in the department of physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka from November, 2019 to April, 2020. A total of 60 female subjects were selected with the age ranging from 25-45 year by purposive sampling. Among them 30 metabolic syndrome patients were included in the study group (group A) and 30 age and sex matched apparently healthy subjects constituted comparison group (group B). Serum homocysteine, vitamin B12, folic acid and other biochemical parameters and the lung function of all subjects were assessed. Data were expressed as mean±SD. Spirometric measures were expressed as percent of predicted value. Statistical analysis was done by Independent sample ‘t’ test and Pearson’s correlation coefficient test. Results: In this study, the mean percentage of predicted value of FVC, FEV1 and, PEFR were significantly lower (p&lt;0.001) in group A than those of group B. The mean serum homocysteine level was higher and vitamin B12 and folic acid level were lower in metabolic syndrome patients compared to comparison group and the difference was statistically significant only for homocysteine (p&lt;0.05). In addition, the FVC and FEV1 were significantly negatively correlated (p&lt;0.05) with serum homocysteine and FVC was significantly positively correlated (p&lt;0.05) with serum folic acid level in group A. Conclusion: The present study reveals that impairment of lung function is related to higher level of homocysteine and lower level of folic acid in metabolic syndrome. Bangladesh Med Res Counc Bull 2021; 47(2): 175-180

MO194: A Rare Case of Secondary Haemolytic Uremic Syndrome after ANTI-SARS-COV-2 Vaccination

Abstract BACKGROUND AND AIMS Haemolytic uremic syndrome (HUS) is a rare disease characterized by macroangiopathic haemolytic anaemia, thrombocytopaenia and severe AKI, belonging to the thrombotic microangiopathies (TMAs). It is divided into typical and atypical HUS: the first one occurs most frequently in children within the first 5 years of life and it is associated with Shiga-like toxin producing Escherichiacoli infection; the second one (aHUS) is less common (10%) and it is due to complement abnormalities with coexisting disease or trigger such as autoimmunity, transplantation, cancer, infection, certain cytotoxic drugs or pregnancy. There is an increasing interest in SARS-CoV-2 infection as new trigger for complement activation. Nine cases of aHUS were recently associated with COVID-19, most of them occurring within 1 month from the infection. Available data suggest that SARS-CoV-2 is a potential trigger for aHUS: it can induce an over inflammatory state and to activate coagulation and complement pathway. Likewise, mRNA-based vaccines against COVID-19 inducing the expression of SARS-CoV-2 spike protein to stimulate immune recognition and antibody response could be a suitable trigger for HUS. METHOD We report the case of a 17-year-old woman, who presented at our emergency department with fever, dyspnoea, acute kidney injury AKI III with anuria, hypertension, severe anaemia, no diarrhoea, severe thrombocytopaenia and myocarditis, about 2 weeks after the first administration of SARS-CoV-2 vaccine (Comirnaty) and recent exposition to SARS-CoV-2 positive individual. SARS-CoV-2 nasal PCR swab was negative (as well as successive ones) and she was immediately admitted to paediatric intensive care unit and treated with transfusions and haemodialysis. Laboratory exams suggested a thrombotic microangiopathy with normal ADAMTS-13 activity and no E. coli infection. She underwent a renal biopsy that confirmed our hypothesis of aHUS: wrinkled capillaries, subendothelial expansion, mesangiolysis and rare thrombi in capillaries lumen. Arterioles had intimal proliferation with mucoid oedema who gave rise to onionskin like lesion that obliterates lumens. One glomerulus showed extracapillary proliferation (crescent), and there was interstitial lymphomonocytic inflammatory infiltration in the nearby. Also signs of acute tubular injury and atrophy were reported. Positive stain to fibrinogen in the arterioles at immunohistology was noted. She immediately performed genetic exams for aHUS-related complement mutations and she started immunosuppression with corticosteroids and eculizumab infusions. After 2 months of eculizumab, she was still oliguric, requiring renal replacement therapy. Genetic analysis showed no mutations. Therefore, she was examined for other genetic causes of thrombotic microangiopathies. RESULTS Finally, came to light that she had high levels of homocysteine, and she was diagnosed with secondary HUS associated with cobalamin C deficiency, which manifests with methylmalonic aciduria and homocystinuria due to a recessive mutation in the MMACHC gene, causing a cobalamin C type deficiency, which is the common functional variant of vitamin B12. After metabolic therapy with hydroxocobalamin, she gradually recovered diuresis and partially renal function without need for replacement therapy. CONCLUSION Reports from immunization programs show as myocarditis and thrombotic thrombocytopaenia are considered among main serious complications caused by COVID-19 vaccines, representing 12.6 cases per million doses and 0.73 cases per 100 000, respectively. This interesting case probably supports data about the role of mRNA-based anti-SARS-CoV-2 vaccines like a precipitant factor for TMAs. Moreover, our patient turned out to be an extremely rare case of HUS secondary to cobalamin C deficiency, that is generally diagnosed in early infancy and show typically neurological symptoms (absent in our case). Probably, the mRNA-based vaccine acted like ‘a second hit’, but existing predisposition should always be investigated including also the less frequent forms.

Risk factors of white matter hyperintensities in migraine patients

BackgroundMigraine frequently is associated with White Matter Hyperintensities (WMHs). We aimed to assess the frequency of WMHs in migraine and to assess their risk factors.MethodsThis is cross-sectional study included 60 migraine patients of both genders, aged between 18 and 55 years. Patients with vascular risk factors were excluded. We also included a matched healthy control group with no migraine. Demographic, clinical data, and serum level of homocysteine were recorded. All subjects underwent brain MRI (3 Tesla).ResultsThe mean age was 38.65 years and most of our cohort were female (83.3). A total of 24 migraine patients (40%) had WMHs versus (10%) in the control group, (P < 0.013). Patients with WMHs were significantly older (43.50 + 8.71 versus. 35.92+ 8.55 years, P < 0.001), have a longer disease duration (14.54+ 7.76versus 8.58+ 6.89 years, P < 0.002), higher monthly migraine attacks (9.27+ 4. 31 versus 7.78 + 2.41 P < 0.020) and high serum homocysteine level (11.05+ 5.63 versus 6.36 + 6.27, P < 0.006) compared to those without WMHs. WMHs were more frequent in chronic migraine compared to episodic migraine (75% versus 34.6%; P < 0.030) and migraine with aura compared to those without aura (38.3% versus 29,2; P < 0.001). WMHs were mostly situated in the frontal lobes (83.4%), both hemispheres (70.8%), and mainly subcortically (83.3%).ConclusionOlder age, longer disease duration, frequent attacks, and high serum homocysteine level are main the risk factors for WMHs in this cohort. The severity or duration of migraine attacks did not increase the frequency of WMHs. The number of WMHs was significantly higher in chronic compared to episodic migraineurs.

Visual Evoked Potentials in Patients With Vitamin B12 Deficiency.

The aim of this study was to investigate the subclinical involvement of the optic nerve in asymptomatic patients with vitamin B12 deficiency using visual evoked potentials. This study included 40 asymptomatic patients diagnosed with vitamin B12 deficiency (considered as serum levels below 150 pg/mL) and a control group of 40 healthy individuals. All participants underwent a visual evoked potential examination. Routine screening for homocysteine was performed for patients with vitamin B12 deficiency. The levels of vitamin B12 and homocysteine and the presence of megaloblastic anemia were analyzed statistically compared with P100, N75, and N135 latencies and amplitudes. The mean vitamin B12 level was 96 pg/mL in the patient group and 374 pg/mL in the control group. In the patient group, 24 (60%) patients had hyperhomocysteinemia and 8 (20%) patients had megaloblastic anemia. The P100 wave latency of patients with vitamin B12 deficiency was significantly prolonged compared with the control group ( P < 0.01). There was no significant difference in the P100 amplitude between the patient group and the control group. P100 latencies were significantly longer in patients with hyperhomocysteinemia ( P = 0.002). Our study showed that patients with vitamin B12 deficiency may have visual evoked potential abnormalities without visual symptoms or examination findings. In addition, high homocysteine levels led to a prolonged P100 latency in the patient group independent of vitamin B12 levels.

Analysis of clinical characteristics and prognostic factors in 110 patients with nitrous oxide abuse.

PurposeTo review the clinical symptoms, auxiliary examination findings, and outcomes of patients with nitrous oxide (N2O) abuse, and analyze the factors that affect outcomes.MethodsPatients with N2O abuse treated in the Department of Neurology between January 2018 and December 2020 were included. The clinical data of these patients were collected, and follow‐up was conducted to determine the outcomes.ResultsThe average age of the 110 patients with N2O abuse was 21.4 ± 4.2 years (range: 14–33 years). Clinical presentation primarily included neurological symptoms, such as limb numbness and/or weakness (97%), psychiatric symptoms, changes in appetite, and skin hyperpigmentation. Laboratory test results were characterized by vitamin B12 deficiency (60%, 34 out of 57 cases) and high homocysteine level (69%, 31 out of 45 cases). Electromyography indicated mixed axonal and demyelination injury (92%, 80 out of 87 cases). Motor and sensory nerves were simultaneously involved, and injury primarily involved the lower limbs. One hundred and seven (97%) patients were clinically diagnosed with peripheral neuropathy, of whom 26 (24%) exhibited spinal abnormalities on magnetic resonance imaging, supporting a diagnosis of subacute combined degeneration. Treatment included N2O withdrawal and vitamin B12 supplementation. Reexamination of six patients indicated that treatment was effective. Follow‐up was completed for 51 patients. Thirty‐four patients (67%) recovered completely, 17 patients (33%) had residual limb numbness, and only one patient experienced relapse. Sex was an independent prognostic factor; the outcomes of female patients were better than that of male patients.ConclusionThe recreational use of N2O has largely expanded among youth in recent decades, which has become a growing public health concern in China. It highlights the importance of the recognition of various clinical symptoms, particularly limb numbness and/or weakness related to the cases of N2O abuse. The therapeutic administration of vitamin B12 supplementation and N2O withdrawal can make the overall prognosis good, especially for female patients.

Evaluation of dietary betaine on post-thawed semen quality in mature bulls during summer heat stress.

Heat stress (HS) has caused relative hypoxia, oxidative stress and high level of homocysteine, which contributes significantly to fertility failures in bulls. The aim of present study was to evaluate the role of dietary betaine (BET) in improving dual purpose Simmental (Fleckvieh) post-thawed semen quality especially during the hottest summer days. A total number of 16 mature bulls were randomly assigned to three equal groups including: 1) Control condition (without betaine), 2) BET1: 57.00 mg of betaine kg-1 per day and 3) BET2: 114 mg of betaine kg-1 per day, through daily intakes for 90 days in summer. Plasma levels of homocysteine, seminal plasma antioxidants levels and sperm parameters such as DNA fragmentation, chromatin integrity, motility, viability, morphology and membrane integrity were evaluated. Under maximal HS, serum homocysteine concentrations were reached 16.67 ± 0.09 µmol L-1. Dietary betaine supplementation influenced DNA fragmentation of sperm and was higher in the control group compared to BET2 group. There were significant decreases in seminal plasma superoxide dismutase (SOD), glutathione peroxidase (GPx) activity and sperm viability and motility in bulls treated with betaine. The activity of GPx and SOD in the control group was increased up to 0.08 ± 0.00 U mg-1 protein and 0.52 ± 0.01 U mg-1 protein in seminal plasma. There were no significant differences between groups in the percentage of swollen spermatozoa, membrane integrity, sperm morphology, abnormal head morphology and percentage of spermatozoa stained with aniline blue. In conclusion, BET supplements improved semen parameters in sperm motility, sperm viability and influenced DNA fragmentation during HS with reduction in serum homocysteine concentrations.

Induction of apoptosis and autosis in cardiomyocytes by the combination of homocysteine and copper via NOX-mediated p62 expression

High levels of homocysteine (Hcy) associated with cardiovascular events are accompanied by increased copper (Cu) concentrations in the blood. Hcy has been shown to promote endothelial dysfunction, whereas the effect of Hcy on cardiomyocytes and the role of Cu in the pathogenesis remain less understood. In the present study, it is demonstrated that the combination of Hcy and Cu2+-induced apoptosis and autosis of cardiomyocytes simultaneously, and thus led to cardiac dysfunction in hyperhomocysteinemic rats. These effects were associated with p22phox activation and NADPH oxidase (NOX)-mediated p62 upregulation. Inhibition of the expression of p22phox or p62 in cardiomyocytes significantly attenuated Hcy and Cu2+-mediated reactive oxygen species (ROS) generation and cell death. Furthermore, interrupting the NOX–p62 axis prevented diastolic dysfunction in hyperhomocysteinemic rats (HcyR). These findings establish that the induction of apoptosis and autosis of cardiomyocytes through stimulating the NOX–p62-signaling pathway constitutes a novel mechanism of Hcy and Cu-induced cardiac dysfunction.

Longitudinal Analysis of 1α,25-dihidroxyvitamin D3 and Homocysteine Changes in Colorectal Cancer.

Simple SummaryVitamin D3 and homocysteine level abnormalities are both strongly related to colorectal cancer (CRC) etiology. The aim of this retrospective study was to investigate the longitudinal change in these two parameters and the relationships between the two, in addition with other clinicopathological and laboratory parameters. A swoosh-shaped trend was observed for the change in serum homocysteine levels of all of the CRC patients. The circulating vitamin D3 level was constant or increased in those patients without metastasis. After an initial increase, the disease-worsening effect of metastases cancelled out all of the positive effects of vitamin D3 in metastatic patients, even despite its continuous supplementation. Right-sided tumors, male sex, and the pathological values of serum lipids, albumin, total protein, and inflammatory markers were associated with lower vitamin D3 and higher homocysteine level. Based on our results, we recommend a modified vitamin D3 supplementation regimen for metastatic CRC, which includes laboratory measurement-based titration.Background: 1α,25-dihydroxycholecalciferol (1,25(OH)2D3) and homocysteine are known to play a role in the pathophysiology of colorectal cancer (CRC). In health, the two changes are inversely proportional to each other, but little is known about their combined effect in CRC. Methods: The serum 1,25(OH)2D3 and the homocysteine levels of eighty-six CRC patients were measured, who were enrolled into four cohorts based on the presence of metastases (Adj vs. Met) and vitamin D3 supplementation (ND vs. D). Results: 1,25(OH)2D3 was constant (Adj-ND), increased significantly (Adj-D, p = 0.0261), decreased (Met-ND), or returned close to the baseline after an initial increase (Met-D). The longitudinal increase in 1,25(OH)2D3 (HR: 0.9130, p = 0.0111) positively affected the overall survival in non-metastatic CRC, however, this effect was cancelled out in those with metastasis (p = 0.0107). The increase in homocysteine negatively affected both the overall (HR: 1.0940, p = 0.0067) and the progression-free survival (HR: 1.0845, p = 0.0073). Lower 1,25(OH)2D3 and/or higher homocysteine level was characteristic for patients with higher serum lipids, albumin, total protein, white blood cell and platelet count, male sex, and right-sided tumors. No statistically justifiable connection was found between the target variables. Conclusions: A measurement-based titration of vitamin D3 supplementation and better management of comorbidities are recommended for CRC.

Endothelial Nitric Oxide Synthase Gene Polymorphisms Increase Risk of Deep Vein Thrombosis by Altering Homocysteine Levels.

Deep Vein Thrombosis (DVT) is a multicausal disease involving both acquired as well as genetic factors. Nitric oxide is an influential endogenous factor having its role in the development of deep vein thrombosis. It maintains the vascular integrity and any alterations in its levels may lead to a thrombotic event. It may also modulate homocysteine metabolism to cause hyperhomocysteinemia, which is a prominent risk factor for thrombosis. The objective of the study was to study if endothelial nitric oxide gene polymorphisms, 894G/T, and 2479G/A alter the plasma nitric oxide and homocysteine levels which may eventually increase the risk of deep vein thrombosis. One hundred Doppler ultrasonography and computerized tomography confirmed (for cerebral venous thrombosis), non-related DVT patients (M:F = 58:42; age range = 18 to 61 years) served as the study population. Two hundred hospital staff and their relatives or unrelated attendants of the patients served as the controls. Nitric oxide levels were determined by measuring its metabolites (NOx), and EIA was used to measure homocysteine levels. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for detecting the eNOS polymorphisms 894G/T and 2479G/A. In total, DVT subjects have 25% higher plasma levels of homocysteine and 37% lower levels of NOx in their circulation when compared to controls. In tertile analysis of nitric oxide and homocysteine levels, 894G/T and 2479G/A polymorphisms were associated with plasma nitric oxide and homocysteine levels. The increased risk of deep vein thrombosis was associated with endothelial nitric oxide gene polymorphisms and nitric oxide levels, but homocysteine levels were not a risk for deep vein thrombosis. The present study demonstrates that 894G/T and 2479G/A polymorphisms interact with lower levels of nitric oxide and higher levels of homocysteine that may possess the risk of deep vein thrombosis.