Supplementation of folic acid and vitamin B12 reduces plasma levels of asymmetric dimethylarginine in patients with acute ischemic stroke.

Increased levels of asymmetric dimethylarginine (ADMA) have been observed in patients with acute ischemic stroke. We aimed to investigate the correlation between ADMA and ischemic stroke, and evaluate the effect of supplementation of folic acid and vitamin B12 on concentrations of ADMA. Patients were randomized into intervention and non-intervention groups within 3 days after symptom onset. Intervention group patients were treated with folic acid (5mg daily) and vitamin B12 (500 µg twice daily) for 12 weeks. ADMA and homocysteine (Hcy) concentrations were measured before treatment (baseline) and 2 and 12 weeks after treatment. The laboratory measures were also collected from healthy controls. Eighty five subjects were enrolled in this study, from whom 72 with complete baseline and follow-up laboratory data were included in the present analysis. Thirty four patients were assigned to the intervention group and 38 patients to the non-intervention group. Sixty people were enrolled as healthy controls. Levels of ADMA and Hcy were raised (p<0.05) in patients with acute ischemic stroke. With supplementation of both folic acid and vitamin B12, the levels of ADMA and Hcy decreased significantly at 2 and 12 weeks (p<0.05). The present study reconfirmed that ADMA can be regarded as a risk biomarker for acute ischemic stroke. We observed that with supplementation of folic acid and vitamin B12, levels of ADMA were decreased in patients with acute ischemic stroke.

Kynurenic acid and 3-hydroxykynurenine production from D-kynurenine in mice.

Kynurenic acid (KYNA), an antagonist of the α7 nicotinic acetylcholine receptor and the N-methyl-D-aspartate receptor, and 3-hydroxykynurenine (3-HK), a generator of reactive oxygen species, are neuroactive metabolites of the kynurenine pathway of tryptophan degradation. In the mammalian brain as elsewhere, both compounds derive from a common bioprecursor, L-kynurenine (L-KYN). Recent studies in rats demonstrated that D-kynurenine (D-KYN), a metabolite of the bacterial amino acid D-tryptophan, can also function as a bioprecursor of brain KYNA. We now investigated the conversion of systemically administered D-KYN to KYNA in mice and also explored the possible production of 3-HK in the same animals. Thirty min after an injection of D-KYN or L-KYN (30 mg/kg, i.p.), newly produced KYNA and 3-HK were recovered from plasma, liver, forebrain and cerebellum in all cases. Using a new chiral separation method, 3-HK produced from D-KYN was positively identified as D-3-HK. L-KYN was the more effective precursor of KYNA in all tissues and also exceeded D-KYN as a precursor of brain 3-HK. In contrast, D-KYN was more potent as a precursor of 3-HK in the liver. The production of both KYNA and 3-HK from D-KYN was rapid in all tissues, peaking at 15-30 min following a systemic injection of D-KYN. These results show that biosynthetic routes other than those classically ascribed to L-KYN can account for the synthesis of both KYNA and 3-HK in vivo. This new insight may be of significant physiological or pathological relevance.

[Local mild hypothermia therapy for neurogenic pulmonary edema].

OBJECTIVE: To investigate the changes in stress hormones in neurogenic pulmonary edema (NPE) and explore the clinical value of mild hypothermia therapy for treatment of NPE. METHODS: Fifty-two patients with cerebral hemorrhage patients and concomitant NPE were randomly divided into two groups for local mild hypothermia therapy (23 cases, LMH group) or routine treatment (29 cases, RT group). In the former group, local mild hypothermia therapy was applied in addition to the routine treatment. The changes of serum corticotrophin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), corticosteroid (Cor), arginine vasopressin (AVP) and blood sugar were observed before and 7 days after the treatment, and compared with those of 58 NPE-free patients with cerebral hemorrhage and 40 healthy individuals. RESULTS: Serum CRH, ACTH, Cor, and AVP levels and blood sugar in NPE patients and the NPE-free patients were all significantly higher than those in the healthy individuals (P<0.01), and the levels were significantly higher in NPE patients than in the NPE-free patients (P<0.05). In the NPE patients, the mortality rate and NIHSS score were significantly lower in RT group (P<0.01); after 7 days of treatment, both LMH and RT groups showed significant reduction in serum CRH, ACTH, Cor, and AVP levels (P<0.05), and the reduction was more conspicuous in LMH group (P<0.05). CONCLUSION: The occurrence of NPE is closely associated with stress reactions, which might be the basis of NPE. Local mild hypothermia therapy improves of the quality of life of NPE patients and also decreases the mortality of NPE possibly by inhibiting the secretion of stress hormones and stabilizing the hypothalamic-pituitary-adrenal axis.

The effects of GM1 and bFGF synergistically inducing adult rat bone marrow stromal cells to form neural progenitor cells and their differentiation.

OBJECTIVE: To investigate the effects of GM1 on inducing adult rat bone marrow stromal cells (MSCs) to form neural progenitor cells and their differentiation. METHODS: Purified MSCs were induced by different components of basic fibroblast growth factor (bFGF) alone, GM1 alone or combination of bFGF with GM1. After 3 days' incubation, fibronectin and collagen I were detected with immunocytochemistry, and nestin was detected with immunofluorescence. Neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP) and galactose cerebroside (GalC) were detected with immunocytochemistry after 7 days' incubation. RESULTS: After induction with bFGF alone or combination of bFGF and GM1, some MSCs exhibited the phenotypes of neural progenitor cells, and then neurons and astrocytes. In these two groups, the positive cells for fibronectin and collagen I decreased markedly after 3 days' induction. At the same time, the positive cells for nestin increased markedly. After 7 days' induction, NSE and GFAP-positive cells increased significantly. Furthermore, the addition of bFGF and GM1 caused the maximal variation. However, addition of GM1 alone had no inductive effects. CONCLUSIONS: Combination of bFGF with GM1 may synergistically promote the transformation of MSCs and differentiation into neurons and astrocyte-like cells. The results suggest a promising route for the application of MSCs.