Distribution of plasma folate forms in hemodialysis patients receiving high daily doses of l-folinic or folic acid

Distribution of plasma folate forms in hemodialysis patients receiving high daily doses of l-folinic or folic acid.BackgroundWe have previously reported that a daily oral high dose of l-folinic acid for the treatment of hyperhomocysteinemia in hemodialysis patients does not provide significantly greater reduction in fasting total homocysteine (tHcy) levels than an equimolar dose of folic acid. The present study uses the affinity/HPLC method to analyze the distribution of plasma folate forms in patients who received l-folinic acid versus those who received folic acid. This was done to investigate claims that renal insufficiency is associated with impaired folate interconversion, a stance that is supportive of the premise that tHcy lowering in these patients is more efficacious with folinic acid and other reduced folates, than folic acid.MethodsForty-eight chronic and stable hemodialysis patients were block-randomized, based on their screening predialysis tHcy levels, sex, and dialysis center, into two groups treated for 12 weeks with oral folic acid at 15 mg/day or an equimolar amount (20 mg/day) of oral l-folinic acid. All 48 subjects also received 50 mg/day of oral vitamin B6 and 1 mg/day of oral vitamin B12. Folate distribution was determined in plasma of 46 participants (Folinic acid group, N = 22; Folic acid group, N = 24) by using the affinity/HPLC method, with electrochemical (coulometric) detection.ResultsBoth groups had similar baseline geometric means of plasma total folate and similar folate forms distribution. Following treatment, both groups demonstrated similar marked elevation in plasma total folate (geometric mean of the increase: Folinic acid group, +337 ng/mL; Folic acid group, +312 ng/mL; P = 0.796). In the folinic acid-treated group, practically all of the increase in total folate was due to 5-methyltetrahydrofolate. In the folic acid-treated group 5-methyltetrahydrofolate accounted for 35% of the increase in total folate and the remainder was unmethylated folic acid.ConclusionsData from the present findings suggest that defects in folate absorption or impairment in folate interconversion are not the cause of the persistent hyperhomocysteinemia in hemodialysis patients

إعداد خرائط الغمر الناجمة عن انهيار مُفترض لسد الباسل نتيجة تدفق الماء فوق قمة السد

تتغير الظروف المناخية وتتزايد حالات الفيضان من حيث التردد والكثافة. يتزايد عدد سكان العالم أيضًا، مما يعني أن الفيضان قد يتسبب في المزيد من الضرر أكثر من قبل. قد يأتي الفيضان نتيجة انهيار السدود مما يسبب خسائر فادحة في الأرواح والممتلكات وأضرار جسيمة في البني التحتية حيث يتم غمر مناطق ومنشآت هامة. تتضمن هذه الدراسة تحليل الموجة الفيضانية الناجمة عن انهيار سد الباسل في محافظة طرطوس باستخدام نموذج هيدروليكي أحادي البعد  HEC-RAS-1D وأداة الـ HEC-GEORAS في برنامج الـ GIS والتي تساعد باستخراج البيانات الطبوغرافية للنهر من الخرائط الطبوغرافية وذلك بهدف رسم خرائط الغمر لتحديد المناطق المتأثرة بهذه الموجة. قمنا بالتنبؤ ببارامترات الخرق باستخدام معادلة Froehlich (1995)، وإدخال هيدروغراف الموجة الفيضانية التصميمية للسد التي تمر كل 10000 سنة مرة كشرط طرفي ومحاكاة انهيار السد نتيجة الجريان غير المستقر وتدفق الماء فوق قمة السد، أظهرت النتائج أن الغزارة الأعظمية الناتجة بعد خمسين دقيقة من بدء الانهيار كانت قيمتها  29606 m3/sec وتراوحت قيم السرع بين الـ  m/sec(3-26) على طول المجرى، كما أظهرت النتائج أن سيناريو تدفق المياه فوق القمة هو سيناريو الانهيار الأخطر

Essential role for Rap1 GTPase and its guanine exchange factor CalDAG-GEFI in LFA-1 but not VLA-4 integrin–mediated human T-cell adhesion

Regulated adhesion of T cells by the integrins LFA-1 (lymphocyte function-associated antigen-1) and VLA-4 (very late antigen-4) is essential for T-cell trafficking. The small GTPase Rap1 is a critical activator of both integrins in murine lymphocytes and T-cell lines. Here we examined the contribution of the Rap1 regulatory pathway in integrin activation in primary CD3+ human T cells. We demonstrate that inactivation of Rap1 GTPase in human T cells by expression of SPA1 or Rap1GAP blocked stromal cell-derived factor-1α (SDF-1α)–stimulated LFA-1–ICAM-1 (intercellular adhesion molecule-1) interactions and LFA-1 affinity modulation but unexpectedly did not significantly affect binding of VLA-4 to its ligand VCAM-1 (vascular cell adhesion molecule 1). Importantly, silencing of the Rap1 guanine exchange factor CalDAG-GEFI inhibited SDF-1α- and phorbol 12-myristate 13-acetate (PMA)–induced adhesion to ICAM-1 while having no effect on adhesion to VCAM-1. Pharmacologic inhibition of Phospholipase C (PLC) blocked Rap1 activation and inhibited cell adhesion and polarization on ICAM-1 and VCAM-1. Protein kinase C (PKC) inhibition led to enhanced levels of active Rap1 concomitantly with increased T-cell binding to ICAM-1, whereas adhesion to VCAM-1 was reduced. Thus, PLC/CalDAG-GEFI regulation of Rap1 is selectively required for chemokine- and PMA-induced LFA-1 activation in human T cells, whereas alternate PLC- and PKC-dependent mechanisms are involved in the regulation of VLA-4