vitamin-b-12 and Sepsis

To analyse the anti-inflammatory and antioxidant properties of vitamin B12 and evaluate current evidence on vitamin B12 status in the critically ill with systemic inflammation.. Data on vitamin B12 status of intensive care unit patients are scarce. Cobalamins could potentially be useful agents for inhibiting nitric oxide synthase and nitric oxide production, controlling nuclear factor-kappa B activation, and restoring optimal bacteriostasis and phagocytosis in which transcobalamins play a proven role. The antioxidant properties of vitamin B12, with a glutathione-sparing effect, are secondary to stimulation of methionine synthase activity and reaction with free oxygen or nitrogen radicals. Large parenteral doses are routinely administered for cyanide poisoning, with only mild, reversible side-effects. Current evidence suggests that high-dose parenteral vitamin B12 may prove an innovative approach to treat critically ill systemic inflammatory response syndrome patients, especially those with severe sepsis/septic shock. In this setting, vitamin B12 and transcobalamins could modulate systemic inflammation contributing to the anti-inflammatory cascade and potentially improve outcome.. Despite evidence from animal studies, so far there are no clinical intervention trials that have studied vitamin B12 as a pharmaconutrient strategy for critical care. Well designed animal and clinical studies are required to clarify several outstanding questions on the optimal posology, safety, and efficacy of high-dose vitamin B12 in the critically ill.

Topics: Animals; Antioxidants; Critical Illness; Humans; Inflammation; Sepsis; Vitamin B 12

In recent years, observational studies have been conducted to investigate the potential impact of vitamins on sepsis. However, many of these studies have produced inconsistent results. Our Mendelian randomization (MR) study aims to evaluate the causality between vitamins and sepsis from a genetic perspective.. Our MR study was designed following the STROBE-MR guidelines. Genetic instrumental variables for vitamins including folate, vitamin B12, B6, A (Retinol), C, D, and K were obtained from previous genome-wide association studies (GWAS) and MR studies. Five different sepsis severity levels were included in the analysis. The genetic instrumental variables were screened for potential confounders using PhenoScanner V2. MR analysis was performed using MR-egger, inverse-variance weighted multiplicative random effects (IVW-RE), inverse-variance weighted multiplicative fixed-effects (IVW-FE), and wald ratio methods to assess the relationship between vitamins and sepsis. Sensitivity analysis was performed using the MR-egger_intercept method, and the MR-PRESSO package and Cochran's Q test were used to evaluate the heterogeneity of the instrumental variables.. Our MR study found no statistically significant association between vitamins and sepsis risk, regardless of the type of vitamin (P-value > 0.05). The odds ratios (ORs) for folate, vitamin B6, vitamin B12, vitamin A, vitamin D, vitamin K, and vitamin C were 1.164 (95% CI: 0.895-1.514), 0.987 (95% CI: 0.969-1.005), 0.975 (95% CI: 0.914-1.041), 0.993 (95% CI: 0.797-1.238), 0.861 (95% CI: 0.522-1.42), 0.955 (95% CI: 0.86-1.059), and 1.049 (95% CI: 0.911-1.208), respectively. Similar results were observed in subgroups of different sepsis severity levels.. Our MR study found no evidence of a causal association between vitamins and sepsis risk from a genetic perspective. Further randomized controlled trials are necessary to confirm these results.

Topics: Folic Acid; Genome-Wide Association Study; Humans; Mendelian Randomization Analysis; Sepsis; Vitamin A; Vitamin B 12; Vitamin K; Vitamins

Introduction and objective: a study was made of the folic acid (Fol) and vitamin B12 (B12) serum concentrations in critical patients with septic shock upon admission and after three days of stay in the Intensive Care Unit (ICU), with an analysis of their association to inflammatory parameters and patient morbidity-mortality. Methods: a prospective analytical study was made of 30 critically ill patients with septic shock. Demographic data, comorbidities, clinical information and severity scores were recorded. Data collected included serum Fol and B12 levels using the DxI® Autoanalyzer (Beckman Coulter) based on a competitive electrochemoluminescence immunoassay. Results: mean serum Fol was within the reference range stipulated by the laboratory on the first day. Nevertheless, a total of 21.4 % of the patients had high Fol levels, with 14.2 % being Fol deficient. An association was observed between Fol (p ˂ 0.012) status and 28-day mortality, and the number of days of mechanical ventilation, fraction of inspired oxygen (FiO2) and fibrinogen increased in patients with higher Fol levels (p ˂ 0.05). In addition, 85.7 % of cases had B12 levels above the reference values, with a correlation being observed between B12 and Fol. Conclusions: this study proposes Fol as a novel morbidity-mortality biomarker in critical septic patients, and reinforces the usefulness of B12 as a morbidity biomarker. It is thus suggested that the measurement of Fol upon admission and over the first 72 hours of hospital stay could provide prognostic information about the clinical course and outcome of septic shock patients.. Introducción y objetivo: se realizó un estudio de las concentraciones séricas de ácido fólico (Fol) y vitamina B12 (B12) en pacientes críticos con shock séptico al ingreso y después de tres días de estancia en la Unidad de Cuidados Intensivos (UCI), con un análisis de su asociación con los parámetros inflamatorios y la morbimortalidad de los pacientes. Método: se realizó un estudio analítico prospectivo de 30 pacientes críticos con shock séptico. Se registraron datos demográficos, comorbilidades, información clínica y puntuaciones de gravedad. Los datos recopilados incluyeron los niveles séricos de Fol y B12 utilizando el autoanalizador DxI® (Beckman Coulter) basado en un inmunoensayo de electroquimioluminiscencia competitivo. Resultados: la media de Fol sérico estuvo dentro del rango de referencia estipulado por el laboratorio el primer día. Sin embargo, el 21,4 % de los pacientes presentaban niveles altos de Fol y el 14,2 % presentaban deficiencia de Fol. Se observó una asociación entre el estado de Fol (p ˂ 0,012) con la mortalidad a los 28 días, con el número de días de ventilación mecánica, con la fracción de oxígeno inspirado (FiO2) y con el fibrinógeno, que aumentaron en los pacientes con niveles de Fol más altos (p ˂ 0,05). Además, el 85,7 % de los casos tenían niveles de B12 por encima de los valores de referencia, observándose una correlación entre B12 y Fol. Conclusiones: este estudio propone al Fol como nuevo biomarcador de morbimortalidad en los pacientes críticos con sepsis y refuerza la utilidad de la B12 como biomarcador de morbilidad. Por tanto, se sugiere que la medición de Fol al ingreso y durante las primeras 72 horas de estancia hospitalaria podría proporcionar información pronóstica sobre el curso clínico y el resultado de los pacientes con shock séptico.

Topics: Biomarkers; Folic Acid; Humans; Intensive Care Units; Morbidity; Prospective Studies; Sepsis; Shock, Septic; Vitamin B 12

To compare serum concentrations of homocysteine in healthy dogs and those fitting the criteria for systemic inflammatory response syndrome and to compare these values to commonly measured B-vitamins.. Study dogs were classified into non-infectious systemic inflammatory response syndrome or sepsis groups and blood was drawn on Day 1 of the patient's hospitalisation for measurement of serum homocysteine, folate and cobalamin concentrations. Homocysteine concentration was measured in 51 clinically healthy dogs to serve as the control group.. A statistically significant difference was found between the homocysteine concentrations of the healthy group when compared to non-infectious systemic inflammatory response syndrome and sepsis groups. Homocysteine values were not correlated with folate, cobalamin or APPLEfast severity scores. Homocysteine concentrations were significantly lower in sick dogs when compared to the control group, which is dissimilar to the human population.. The clinical significance of homocysteine changes in critically ill dogs is currently unknown.

Topics: Animals; Case-Control Studies; Dog Diseases; Dogs; Female; Folic Acid; Homocysteine; Male; Sepsis; Systemic Inflammatory Response Syndrome; Vitamin B 12

The ideal live vaccine to control Salmonella in commercial chicken flocks should engender protection against various strains. The purpose of the present study was to confirm the attenuation of a Salmonella Gallinarum (SG) mutant strain with deletion on genes cobS and cbiA, that are involved in the biosynthesis of cobalamin. Furthermore, evaluate its use as a live vaccine against Salmonella. For the evaluation of the vaccine efficacy, two experiments were conducted separately. Birds from a commercial brown line of chickens were used to perform challenge with SG wild type strain and birds from a commercial white line of chickens were used to perform challenge with Salmonella Enteritidis (SE) wild type strain. In both experiments, the birds were separated in three groups (A, B and C). Birds were orally vaccinated with the SG mutant as the following programme: group A, one dose at 5 days of age; group B, one dose at 5 days of age and a second dose at 25 days of age; and group C, birds were kept unvaccinated as controls. At 45 days of age, birds from all groups, including the control, were challenged orally by SG wild type (brown line) or SE wild type (white line). Lastly, another experiment was performed to evaluate the use of the SG mutant strain to prevent caecal colonization by SE wild type on 1-day-old broiler chicks. Mortality and systemic infection by SG wild type strain were assessed in brown chickens; faecal shedding and systemic infection by SE wild type were assessed in white chickens and caecal colonization was assessed in broiler chicks. Either vaccination with one or two doses of SG mutant, were capable to protect brown chickens against SG wild type. In the experiment with white chickens, only vaccination with two doses of SG mutant protected the birds against challenge with SE wild type. Although, SG mutant could not prevent caecal colonization in 1-day-old broiler chicks by the challenge strain SE wild type. Overall, the results indicated that SG mutant is a promising Salmonella live vaccine candidate that demonstrated good efficacy to control the infection by two serotypes of major importance to the poultry industry.

Topics: Administration, Oral; Animals; Bacterial Proteins; Chickens; Female; Gene Deletion; Poultry Diseases; Salmonella; Salmonella Infections, Animal; Salmonella Vaccines; Sepsis; Survival Analysis; Vaccines, Attenuated; Virulence Factors; Vitamin B 12

There is considerable evidence that elevated plasma homocysteine levels are associated with a prothrombotic milieu, whereas activation of the coagulation cascade is an important component of the pathogenesis of sepsis. The protein C pathway has been reported to play a central role both in the propagation of sepsis and a hyperhomocysteinemia-induced hypercoagulable state. Our primary aim was to measure plasma homocysteine levels in mechanically ventilated patients with severe sepsis/septic shock and to assess the association of these levels with relevant clinical outcomes.. The study cohort included 102 mechanically ventilated patients with severe sepsis or septic shock. Demographics, comorbidities, clinical data and severity scores were recorded. Plasma homocysteine, vitamin B12, folate, creatinine, and protein C levels were measured in all study subjects upon enrollment, and genotyping for the C677T and A1298C polymorphisisms of the methylenetetrahydrofolate reductase (MTHFR) gene and for factor V Leiden (FVL) mutations was performed as well. The primary outcomes were mortality at 28 and 90 days; secondary outcomes included the number of days without renal or cardiovascular failure and the ventilator-free days during the study period.. Homocysteine levels were not significantly associated with any primary or secondary outcomes in the multivariable analysis. In addition, a synergistic effect of homocysteine with protein C levels was not detected.. Our data suggest that plasma homocysteine levels may not inform the prognosis of mechanically ventilated patients with severe sepsis/septic shock.

Topics: Activated Protein C Resistance; Aged; Blood Coagulation Tests; Cohort Studies; Comorbidity; Factor V; Female; Folic Acid; Homocysteine; Homocystinuria; Hospital Mortality; Humans; Hyperhomocysteinemia; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Muscle Spasticity; Point Mutation; Protein C; Psychotic Disorders; Respiration, Artificial; Sepsis; Shock, Septic; Thrombophilia; Vitamin B 12

Cobalamin carrier proteins,the Transcobalamins (TCS), are elevated during trauma, infections and chronic inflammatory conditions. This remains un-explained. It is proposed that such TC elevations signal a need for cobalamin central to the resolution of inflammation. Thus Cobalamin may regulate the transcription factor, NFkappaB, activation or suppression of which determines the inflammatory response and its resolution. Such regulation may involve at least 5 separate mechanisms: (i) hormone-like regulation of TNFalpha, through reduction of excess NO by cobalamin, as well as through the selective inhibition, in tandem with glutathione, of inducible nitric oxide synthase; (ii) quenching of nitric oxide radicals and reactive oxygen species, enhanced by cobalamin's glutathione sparing effect; (iii) the promotion of acetylcholine synthesis, central to the neuro-immune cholinergic anti-inflammatory pathway; (iv) the promotion of oxidative phosphorylation; (v) and a bacteriostatic role of the TCS released by neutrophil secondary granules during phagocytosis, which also appears to modulate the inflammatory response. TC elevations are dependent on NFkappaB activation, through crosstalk between NFkappaB and Sp1, another member of the helix-loop-helix protein family, which directly mediates transcription of the TCII gene. Sp1 also has binding sites on the TNFalpha and EGF gene promoters. NFkappaB may thus ensure sufficient cobalamin to determine its own eventual suppression. Cobalamin's established regulation of EGF may additionally preserve normal function of macrophages and the coagulation cascade in wound healing. By regulating NFkappaB, Cobalamin may also be the as yet unidentified mediator needed to potentiate the anti-inflammatory action of eicosanoids derived from omega-3 essential fatty acids. Moreover, animal and human clinical data suggests that high dose cobalamin may prove a promising approach to SIRS/sepsis/septic and traumatic shock.

Topics: Acetylcholine; Glutathione; Humans; Inflammation; Models, Biological; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase; Sepsis; Shock, Septic; Shock, Traumatic; Systemic Inflammatory Response Syndrome; Vitamin B 12

Topics: Animals; Bone Marrow; Bone Marrow Cells; Enterobacteriaceae; Female; Hematopoiesis; Hemorrhagic Disorders; Intestines; Kidney; Lymph Nodes; Male; Palatine Tonsil; Radiation Effects; Radiation Injuries, Experimental; Sepsis; Spleen; Swine; Testis; Vitamin B 12

Topics: Animal Diseases; Animals; Diet; Fishes; Hemorrhage; Liver; Mortality; Sepsis; Spleen; Virus Diseases; Vitamin B 12; Vitamin E

Topics: Adolescent; Anemia; Anemia, Hypochromic; Anemia, Macrocytic; Breast Neoplasms; Bronchopneumonia; Child; Deficiency Diseases; Female; Folic Acid; Gastroenterology; Geriatrics; Hemorrhage; Humans; Liver Diseases; Liver Extracts; Multiple Myeloma; Nucleosides; Postpartum Hemorrhage; Postpartum Period; Rheumatic Fever; Sepsis; Toxicology; Virus Diseases; Vitamin B 12; Vitamin B Complex

Topics: Bacterial Infections; Corrinoids; Diphtheria; Guinea Pigs; Sepsis; Toxemia; Vitamin B 12

Topics: Bacterial Infections; Corrinoids; Diphtheria; Sepsis; Toxemia; Vitamin B 12