Effect of short- and long-term treatment with omeprazole on the absorption and serum levels of cobalamin

AIMS: To evaluate absorption of protein-bound and unbound cyanocobalamin before and during treatment with omeprazole, and cobalamin levels in patients on long-term treatment with omeprazole. METHODS: In eight former duodenal ulcer patients absorption of unbound and protein-bound cobalamin was determined by measuring 24-h urinary excretion of unbound 58Co-cyancobalamin or protein-bound 57Co-cyanocobalamin during a modified Schilling test. Tests were performed before and during treatment with 20 mg and 40 mg omeprazole daily for 9 days. Serum cobalamin levels were assessed in 25 patients with gastro-oesophageal reflux disease (GERD) before and during long-term maintenance therapy with omeprazole. Mean treatment duration was 56 months (range 36-81 months). RESULTS: Urinary excretion of unbound cobalamin was unchanged with both dosages of omeprazole. Excretion of 57Co-cyanocobalamin, however, decreased significantly during treatment with both 20 mg omeprazole (mean +/- S.E.M.: 1.31 +/- 0.20 vs. 0.54 +/- 0.17%; P < 0.02) and 40 mg omeprazole (1.25 +/- 0.26 vs. 0.29 +/- 0.06%; P < 0.02). Mean serum cobalamin levels (+/- S.E.M.) before and during therapy with omeprazole in GERD patients were 298 +/- 27 and 261 +/- 16 pg/mL (normal range 180-900 pg/mL), respectively (P = N.S.). CONCLUSIONS: Absorption of protein-bound, but not unbound, cyanocobalamin is decreased when measured by a modified Schilling test during treatment with omeprazole. However, no change in serum cobalamin levels was observed in patients with GERD after treatment with omeprazole for up to 7 years.     

Serum methylmalonic acid and total homocysteine in patients with suspected cobalamin deficiency: a clinical study based on gastrointestinal histopathological findings

We compared the sensitivity and specificity of the two metabolite tests, methylmalonic acid (MMA) and total homocysteine (Hcy) in serum, and serum cobalamin (Cbl) in patients referred to our hospital because of suspected cobalamin deficiency and a serum cobalamin value at the referring unit <200 pmol/L. All 111 patients included were investigated using upper gastrointestinal endoscopy with biopsy specimens taken from the gastric and duodenal mucosa to find a morphological basis for cobalamin malabsorption as well as the Schilling test for the validation of the serum tests. All patients were treated with cobalamin and new blood samples were taken after 4 weeks. We found no difference in sensitivity and specificity between serum MMA, Hcy, and Cbl in identifying patients with and without conditions compatible with cobalamin malabsorption. Elevated serum MMA and Hcy were also found in about 15% of the group of patients with normal Schilling tests and without a morphological basis for cobalamin malabsorption. Moreover, most patients in this group responded with decreased values of the metabolite tests following cobalamin treatment, suggesting that neither elevated metabolites nor a decrease in these values following cobalamin treatment are specific for cobalamin deficiency.     

Screening elderly populations for cobalamin (vitamin B12) deficiency using the urinary methylmalonic acid assay by gas chromatography mass spectrometry

PURPOSE: This study assesses the value of the urinary methylmalonic acid (MMA) assay by gas chromatography mass spectrometry as a screening procedure for detection of cobalamin (Cbl) deficiency and estimates the prevalence of undetected Cbl deficiency in elderly populations. SUBJECTS AND METHODS: A total of 809 elderly individuals over age 65 were screened using random spot urine specimens from 4 different sites: a health fair, retirement apartments, a hospital-based elderly assessment center, and a nursing home. Follow-up tests included serum total Cbl, serum MMA, and normalization of urinary and serum MMA levels with Cbl intramuscular (IM) therapy. RESULTS: The prevalence of elevated urinary MMA varied across population groups, from 3.0% in elderly visiting a health fair to 5.1% in elderly residing in retirement apartments. Follow-up on 35 of 36 subjects with elevated urinary MMA levels showed that 18 had low serum total Cbl (less than 180 pg/mL at Hospital 1 or less than 200 pg/mL at Hospital 2), 12 had low-normal Cbl (180 or 200 pg/mL to 350 pg/mL), and 5 had normal Cbl. Of the 12 subjects with low-normal Cbl on retesting, further assessment was performed in 7, and all 7 of these subjects had evidence of Cbl deficiency. Cbl IM therapy was initiated for 23 subjects; 16 were seen for follow-up and all had normal urinary MMA. CONCLUSION: The relatively high prevalence of undetected Cbl deficiency identified in the seniors warrants additional studies of elderly populations. The sensitivity, convenience, and noninvasive nature of the urinary MMA assay by gas chromatography mass spectrometry make it a practical screening test.     

Atherogenesis and the homocysteine-folate-cobalamin triad: do we need standardized analyses?

BACKGROUND: Bioscientists, physicians and nutritionists are newly interested in the homocysteine-folate-cobalamin triad, in part because homocysteine may be important both in atherogenesis and thrombogenesis. Homocysteine imbalance may be an early marker for cobalamin disorders because cobalamin is a cofactor in remethylation of homocysteine to methionine. METHODS: In 139 men and 32 women of similar mean age of 65 years, we measured markers which have been cited as risk for atherosclerosis: serum homocysteine, folate, total cobalamin, holotranscobalamin I and II, (TCI and TCII), total serum cholesterol (SCHOL), high density lipoprotein cholesterol (HDLC), triglycerides (STG) as well as red blood cell (RBC) folate, food records and body composition by whole body counting of potassium-forty (40K). RESULTS: Statistical relationships among the data showed healthy women had lower mean serum homocysteine and their mean RBC folate and TCI and TCII were higher than men. Eighty-three subjects had TCII much lower than 60 pg/ml (subnormal), yet only 11 of these men and two women had total cobalamin < 200 pg/ml (abnormal). Fifty-two subjects with serum homocysteine greater than 17.5 nmol/ml had TCII less than 60 pg/ml, suggesting serum homocysteine may be a marker for early cobalamin negative balance. None of the subjects in the study had serum folate below abnormal values, i.e., less than 1.6 mg/ml. All subjects had RBC folate within normal range. Serum homocysteine showed inverse relationship with RBC folate and serum total cobalamin, TCI and TCII. CONCLUSIONS: 1) importance of using serum holotranscobalamin TCI and TCII as markers of cobalamin deficiency, 2) necessity to use documented quantitative components of dietary intake if strong comparisons are to be made among quantitative values of serum or plasma homocysteine, folate, cobalamin, and nutrients in food intake.     

Age- and gender-specific reference intervals for total homocysteine and methylmalonic acid in plasma before and after vitamin supplementation

We present reference intervals for total homocysteine and methylmalonic acid in plasma based on samples from 126 women (ages 20-85 years, median 49 years) and 109 men (ages 20-84 years, median 50 years). The central 0.95 interval for methylmalonic acid was 0.08-0.28 micromol/L. Supplementation with cyanocobalamin caused a nonsignificant decrease in methylmalonic acid. Supplementation with folic acid caused a decrease in homocysteine concentrations, with data analysis identifying two significantly different clusters: 182 subjects with the lowest initial concentrations (7.76 +/- 1.54 micromol/L, mean +/- SD) and the smallest decrease (1.26 +/- 0.96 micromol/L), and 53 subjects with the highest initial concentrations (12.33 +/- 2.04 micromol/L) and greatest decrease (4.14 +/- 1.32 micromol/L). We argue in favor of the age- and gender-specific central 0.95 intervals obtained for the 182 subjects before being supplemented with folic acid: 4.6-8.1 micromol/L for subjects at <30 years; 4.5-7.9 micromol/L for women, ages 30-59 years; 6.3-11.2 micromol/L for men, ages 30-59 years; and 5.8-11.9 micromol/L for subjects at >60 years.     

The effect of upper cervical or sacroiliac manipulation on hip flexion range of motion

BACKGROUND: Low serum cobalamin levels are often found in apparently normal older subjects. A major worry of leaving cobalamin deficiency untreated is that it may lead to subtle deterioration in cognitive function. OBJECTIVES: To investigate the effect of supplementation on the cognitive function of older people with cobalamin deficiency by a randomized trial. METHODS: Fifty Chinese subjects more than 60 years old with serum cobalamin level < 120 pmol/l were randomized into supplement and control groups. Fasting serum methylmalonic acid levels (MMA) were measured. A battery of neuropsychological tests was administered. The supplement group received intramuscular cyanocobalamin injections, while the control group received no intervention. They were followed up at around 4 months. RESULTS: 78% of the subjects had raised MMA, indicating metabolic cobalamin deficiency. Supplemented subjects improved in performance IQ, but the amount of improvement was not significantly more than that of control subjects. Moreover, the supplement group fared worse than the control group at follow-up in some motor function scores. Three out of seven demented subjects had improvement in Mini-Mental State Examination scores, but there was no consistent improvement in other neuropsychological scores. CONCLUSIONS: This study suggested that cobalamin deficiency did not invariably cause cognitive impairment in older people. There remain the possibilities that cobalamin deficiency causes cognitive impairment or exacerbates coexisting dementia in some older people.     

Cerebrospinal fluid methylmalonic acid concentrations in neurological patients with low and normal serum cobalamin concentrations

OBJECTIVE: To determine whether cerebrospinal fluid (CSF) methylmalonic acid (MMA) is increased in neurological patients with low serum cobalamin (Cbl, vitamin B12) concentrations as opposed to neurological patients with normal serum Cbl concentrations. MATERIAL AND METHODS: We measured MMA concentrations in serum and CSF of neurological patients with low serum cobalamin concentrations, but without overt cobalamin related manifestations such as anemia or combined disease of the cord, and neurological patients with normal serum cobalamin concentrations (controls). RESULTS: Serum and CSF MMA concentrations were significantly higher in patients than in controls. Serum MMA was elevated in 4 patients of whom 3 had clearly elevated CSF MMA concentrations. CONCLUSION: Strong indications for cobalamin deficiency can be found not only in serum but also in CSF of patients with seemingly asymptomatic low serum cobalamin concentrations.     

Correlation between total homocysteine and cyclosporine concentrations in cardiac transplant recipients

Increased circulating total homocysteine (tHcy) has been implicated as an independent risk factor for atherosclerotic disease. In cardiac transplant patients, accelerated coronary atherosclerosis is an important cause of late allograft failure; however, studies of tHcy in this at-risk group are limited. We sampled a cohort of 72 subjects 3.95+/-3.14 (mean +/- SD) years after transplantation and found that all had tHcy concentrations above our upper reference limit (15.0 micromol/L). The mean tHcy in the transplant group (25.4+/-7.1 micromol/L) was significantly greater than in our reference group (9.0+/-4.3 micromol/L; n = 457; P <0.001). We also examined the effect of age, gender, time since transplant, serum folate and cobalamin, total protein, urate, creatinine, albumin, and trough whole blood cyclosporine concentrations. In a multiple linear regression model, only creatinine (mean 144+/-52 micromol/L; P = 0.021) and trough cyclosporine concentrations (191+/-163 microg/L; P = 0.015) were independent positive predictors of tHcy, whereas serum folate (8.35+/-7.43 nmol/L; P = 0.018) and time since transplant (P = 0.049) were significant negative predictors. We conclude that hyperhomocysteinemia is a common characteristic of cardiac transplant recipients. Our analysis suggests that folate and renal glomerular dysfunction are important contributory factors; however, whole blood cyclosporine concentrations may also predict the degree of hyperhomocysteinemia in this population and therefore influence interpretation of any apparent response to treatment.     

Maternal folate status during extended lactation and the effect of supplemental folic acid

BACKGROUND: Folate requirements during lactation are not well established. OBJECTIVE: We assessed the effects of dietary and supplemental folate intakes during extended lactation. DESIGN: Lactating women (n = 42) were enrolled in a double-blind, randomized, longitudinal supplementation trial and received either 0 or 1 mg folic acid/d. At 3 and 6 mo postpartum, maternal folate status was assessed by measuring erythrocyte, plasma, milk, and dietary folate concentrations; plasma homocysteine; and hematologic indexes. Infant anthropometric measures of growth, milk intake, and folate intake were also assessed. RESULTS: In supplemented women, values at 6 mo for erythrocyte and milk folate concentrations and for plasma homocysteine were not significantly different from those at 3 mo. In supplemented women compared with unsupplemented women at 6 mo, values for erythrocyte folate (840 compared with 667 nmol/L; P < 0.05), hemoglobin (140 compared with 134 g/L; P < 0.02), and hematocrit (0.41 compared with 0.39; P < 0.02) were higher and values for reticulocytes were lower. In unsupplemented women, milk folate declined from 224 to 187 nmol/L (99 to 82 ng/mL), whereas plasma homocysteine increased from 6.7 to 7.4 micromol/L. Dietary folate intake was not significantly different between groups (380+/-19 microg/d) and at 6 mo was correlated with plasma homocysteine in unsupplemented women (r = -0.53, P < 0.01) and with plasma folate in supplemented women (r = 0.49, P < 0.02). CONCLUSIONS: A dietary folate intake of approximately 380 microg/d may not be sufficient to prevent mobilization of maternal folate stores during lactation.     

Resistance machine for power skating of hockey players

A 3-month-old male infant had two episodes of fever, projectile vomiting, dehydration, generalized fine tremors and gross metabloic ketoacidosis. Methylmalonic acid was found in high concentration in both serum and urine, although the concentration of serum vitamin B12 was normal. A therapeutic trial of vitamin B12, administered parenterally, reduced greatly the methylmalonic aciduria. The patient has since been given vitamin B12 supplements continuously, initially 1 mg intramuscularly every other day, then 15 mg/d orally, and the protein in his diet was subsequently restricted. The most effected control of the methylmalonic aciduria was achieved with the combined regimen of oral vitamin therapy and dietary protein restriction. His physical and intellectual development have progressed normally and he has survived several acute respiratory tract infections without recurrence of metabolic acidosis.     

Limbal cell autograft transplantation for severe ocular surface disorders

OBJECTIVE: To determine if poor dietary intake can explain the cobalamin-related abnormalities often seen in the elderly. DESIGN: Prospective laboratory survey with a follow-up dietary assessment. SETTING: Social centers for the elderly and an outpatient clinic. SUBJECTS: Ninety-five free-living subjects >60y old with abnormal or suspicious findings in cobalamin-related tests and 78 subjects >60y old with normal results. INTERVENTIONS: Serum cobalamin, methylmalonic acid and homocysteine determinations to assess cobalamin status and a one year food-frequency questionnaire to assess cobalamin intake. RESULTS: Only three of the 173 subjects (1.7%), one of whom had normal cobalamin status, ingested <2 microg cobalamin/d, the Recommended Daily Allowance. Sixty-nine subjects (39.9%) ingested <6 microg/d, but they did not have more abnormal serum cobalamin or metabolite values than those ingesting >6 microg. Ordering all subjects by quintiles according to cobalamin intake revealed no significant trends or differences in any of the serum values either. Moreover, arranging subjects by results of tests of cobalamin status showed that the subjects with abnormal cobalamin status did not differ in cobalamin intake from those with normal cobalamin status, although they did differ in use of supplements. Finally, cobalamin intake, with or without supplements, did not correlate with serum cobalamin or metabolite levels. The absence of any association between cobalamin status and intake contrasts sharply with the significant correlation between folate intake and folate status (P = 0.0001). CONCLUSIONS: The high frequency of mildly abnormal cobalamin status in the elderly cannot be attributed to poor intake of cobalamin. Nondietary explanations, such as malabsorption and other phenomena, must always be sought to explain mild cobalamin deficiency in the elderly.     

Biochemical epidemiology of gallbladder cancer

To evaluate the a priori hypotheses that an increased level of glyco and tauro lithocholic acid, perhaps because of a decreased capacity for hepatic sulfation, contributed to the biochemical epidemiology of gallbladder cancer, a case-control study was undertaken at four hospitals in La Paz, Bolivia, and at one hospital in Mexico City, Mexico. Eighty-four cases with newly diagnosed histologically confirmed gallbladder cancer were compared with 264 controls with cholelithiasis or choledocholithiasis in the absence of cancer and with 126 controls with normal biliary tracts. All study subjects were undergoing abdominal surgery. Interview data were collected for all study subjects, as well as blood, bile, and gallstone specimens when feasible. Sera were analyzed for carcinoembryonic antigen, cholesterol concentration, and total bile acids. Bile specimens were analyzed for carcinoembryonic antigen; and for concentration of bile salts; cholesterol; phospholipids; and the glycine and taurine conjugates of cholic, ursodeoxycholic, chenodeoxycholic, deoxycholic, and lithocholates; sulfoglycolithocholate; and sulfotaurolithocholate. Gallstone specimens were analyzed for the percentage of cholesterol content, the percentage of calcium bilirubinate content, and the percentage of calcium carbonate content. Serum bile acids were increased in cases versus the two control groups (median 11.7 nmol/mL vs. 9.3 nmol/mL for stone controls and 8.2 nmol/L for nonstone controls, P < or = .02 for each pairwise comparison). Biliary bile acids were markedly decreased in the cases (median 3.98 micromol/mL vs. 33.09 micromol/mL, and 154.0 micromol/L, respectively, P < or = .0001 for each comparison), even after excluding those with a serum bilirubin higher than 2.0 mg/dL. Bile cholesterol was lower for the cases as well (median 1.70 micromol/mL vs. 4.90 micromol/mL, and 16.81 micromol/ mL, respectively, P < or = .02), as was the concentration of bile phospholipids (median 2.97 micromol/mL vs. 6.26 micromol/mL, and 52.69 micromol/mL, P = .1 and .0004, respectively). Contrary to our a priori hypothesis, there was no difference between the cases and either control group in their bile concentrations of lithocholate, the proportion of bile acids which were sulfated, or the concentration of nonsulfated lithocholate. However, the cases had a higher concentration of ursodeoxycholate (UDC) (P < .004 for both control groups), especially glycoursodeoxycholate (P < .001 for both control groups). A previously published suggestion that gallstone size differed between cases and controls was not confirmed. In conclusion, cases with gallbladder cancer differed from controls with stones and from controls with normal biliary tracts in their serum and bile biochemistries. These findings may be a reflection of the disease process, or may provide useful clues to its pathogenesis.     

Do androgens regulate growth hormone-binding protein in adult man?

To determine whether adult serum GH-binding protein (GHBP) is regulated by androgen, serum GHBP concentrations were compared between 20 normal and 18 hypogonadal men matched for age and body mass index, and the effect of im testosterone treatment (250 mg testosterone enanthate) on GHBP levels in the 18 hypogonadal men was studied. Nine of the hypogonadal subjects had coexistent GH deficiency. Serum GHBP concentration was measured by a ligand immunofunctional assay. The mean serum GHBP level in untreated hypogonadal men was not significantly different from that of normal men (0.98 +/- 0.15 vs. 1.17 +/- 0.16 nmol/L). The mean serum insulin-like growth factor I (IGF-I) level was significantly lower in the hypogonadal men (132 +/- 22 vs. 206 +/- 17 ng/mL; P < 0.01). Basal testosterone (3.7 +/- 0.7 nmol/L) in hypogonadal men increased during treatment to a mean level of 29.1 +/- 2.8 nmol/L, which was not significantly higher than that in normal men (22.6 +/- 1.9 nmol/L). The mean serum GHBP level in hypogonadal men fell significantly during treatment to 0.60 +/- 0.11 nmol/L (P = 0.0003), whereas the serum IGF-I level rose significantly to 151 +/- 26 ng/mL (P < 0.04). The decrease in GHBP level was significant in both the GH-sufficient and GH-deficient subjects (P < 0.02 in both instances), whereas the increase in IGF-I level was significant in the GH-sufficient group (199 +/- 22 to 235 +/- 29 ng/mL; P < 0.04) but not in the GH-deficient group (53 +/- 7 to 55 +/- 5 ng/mL; P > 0.8). Thus, serum GHBP is normal in hypogonadal men but is reduced by testosterone treatment irrespective of endogenous GH-secretory status. It was concluded that the effect of testosterone on GHBP is pharmacological and occurs independent of GH mediation.     

Hyperhomocysteinemia and atherosclerotic vascular disease: pathophysiology, screening, and treatment. off

Hyperhomocysteinemia has recently been identified as an important risk factor for atherosclerotic vascular disease. This article reviews homocysteine metabolism, causes of hyperhomocysteinemia, the pathophysiological findings of this disorder, and epidemiological studies of homocysteine and vascular disease. Screening for hyperhomocysteinemia should be considered for patients at high risk for vascular disease or abnormalities of homocysteine metabolism. For primary prevention of vascular disease, treatment of patients with homocysteine levels of 14 micromol/L or higher should be considered. For secondary prevention, treatment of patients with homocysteine levels of 11 micromol/L or higher should be considered. Treatment is most conveniently administered as a folic acid supplement (400-1000 microg) and a high-potency multivitamin that contains at least 400 microg of folate. Higher doses of folic acid and cyanocobalamin supplements may be required in some patients. Until prospective clinical trial data become available, these conservative recommendations provide a safe, effective, and evidence-based approach to the diagnosis, evaluation, and management of patients with hyperhomocysteinemia.     

Hyperhomocysteinaemia--a common finding in a psychogeriatric population

Plasma homocysteine concentration is a sensitive marker for cobalamin and folate deficiency. The previously reported high incidence of increased plasma homocysteine in psychogeriatric patients and the association between reduced concentrations of cobalamin, folate and neuropsychiatric symptoms led to the present study on 741 consecutive psychogeriatric patients. The concentrations of plasma homocysteine correlated significantly with blood folate, serum cobalamin and serum creatinine both in demented (n = 295) and in non-demented patients with other psychiatric disorders (n = 215). Plasma homocysteine concentrations were significantly increased in both the demented and the non-demented patients, whereas only the demented patients had lower blood folate and serum creatinine concentrations than 163 control subjects. Almost all of the different diagnostic groups of demented and non-demented patients exhibited significantly increased plasma homocysteine concentrations compared with control subjects. Significantly decreased blood folate concentrations were mainly found in the different diagnosis groups of demented patients. Plasma homocysteine concentrations in both demented and non-demented patients with serum cobalamin and blood folate above the lower 20th percentile of these vitamins in the control subjects were also studied. Despite these vitamin concentrations, both groups of patients still exhibited significantly higher plasma homocysteine concentrations than the control subjects, which may indicate an increased frequency of impaired genetic capacity to metabolize homocysteine in these patients. Patients with either dementia of vascular cause or a history of other occlusive arterial disease had a significantly higher plasma homocysteine concentration than those without a history of vascular disease.     

Shopping in the healthcare information systems market--a search for well-camouflaged land mines

Proton MR spectra of the basal ganglia were obtained from 28 patients, 24 male and 14 female, median age 16.3 months (5 weeks to 31 years). They included 17 patients with normal MRI of the basal ganglia without metabolic disturbance (control group) and 11 patients with various metabolic diseases: one case each of high serum sodium and high serum osmolarity, cobalamin C deficiency, Leigh disease, Galloway-Mowat syndrome, Pelizaeus-Merzbacher disease, hemolytic-uremic syndrome and Wilson disease and two cases of Alagille syndrome and methylmalonic acidemia with abnormal MRI of the basal ganglia or blood or urine analysis (abnormal group). The MR spectrum was measured by using STEAM. The MR-visible water content of the region of interest was obtained. Levels of myoinositol, choline, creatine and N-acetylaspartate were measured using a semiquantitative approach, with absolute reference calibration. In the control group, there was a gradual drop of water content over the first year of life; N-acetylaspartate, creatine and myoinositol levels showed no significant change with age, in contrast to the occipital, parietal and cerebellar regions. Choline showed a gradual decrease for the first 2 years of life and then remained fairly constant. In the abnormal group the water content was not significantly different. N-Acetylaspartate was decreased in patients with high serum sodium and high serum osmolarity, cobalamin C deficiency, Leigh disease and one case of methylmalonic acidemia. Decreased creatine was also found in Leigh disease, and decreased choline in Galloway-Mowat syndrome and Wilson disease. Myoinositol was elevated in the patient with abnormally high serum sodium, and decreased in the hemolytic-uremic syndrome.     

De novo epileptic confusional status in a patient with cobalamin deficiency

A 80-year-old man with cobalamin deficiency and no history of epilepsy developed a partial complex epileptic confusional status (ECS) unresponsive to acute i.v. diazepam. Brain CT scan and MRI investigation ruled out a focal cerebral lesion. Therapy with high doses (10,000 micrograms i.m. daily) of cobalamin alone was started, and the patient fully recovered in the following 72-hour. Control EEGs repeatedly performed days and weeks later showed progressive disappearance of the frontal interictal spiking, while the patient was on monotherapy with cobalamin (5,000 micrograms i.m. weekly). A month later the patient unfortunately discontinued replacement therapy and 13 weeks later he developed a fatal convulsive epileptic status. To our knowledge the association of ECS and cobalamin deficiency has not been previously reported.     

Effect of catechin on carbohydrate metabolism

The serum free carnitine levels of 33 children with recurrent pulmonary infection and 30 healthy children were measured and found to be 26.12 +/- 0.98 nmol/mL and that of the control group 38.98 +/- 0.79 nmol/mL on the average. The mean free carnitine level was statistically determined to be significantly lower when compared with that of the control group (P < 0.01). The results indicate that oral L-carnitine therapy is recommended for pediatric patients with recurrent pulmonary infection.     

Biosynthesis of a cyclic tautomer of (3-methylmaleyl)acetone from 4-hydroxy-3,5-dimethylbenzoate by Pseudomonas sp. HH35 but not by Rhodococcus rhodochrous N75

Vitamin E is one of the most important lipid-soluble antioxidant nutrients. Severe vitamin E deficiency can have a profound effect on the central nervous system. Cystic fibrosis, chronic cholestatic liver disease, abetalipoproteinemia, short bowel syndrome, isolated vitamin E deficiency syndrome and other malabsorption syndromes all may cause varying degrees of neurologic deficits due to related vitamin deficiencies. The classic abnormalities in vitamin E deficiency progress from hyporeflexia, ataxia, limitations in upward gaze and strabismus to long-tract defects, profound muscle weakness and visual field constriction. Patients with severe, prolonged deficiency may develop complete blindness, dementia and cardiac arrhythmias. Treatment must be tailored to the underlying cause of vitamin E deficiency and may include oral or parenteral vitamin supplementation. The more advanced the deficits, the more limited the response to therapy. Therefore, a good neurologic examination and periodic serum vitamin E levels are essential in patients at risk of vitamin E deficiency.     

Mechanism of Immune Hyporesponsiveness Induced by Recipient-derived Immature Dendritic Cells in Liver Transplantation Rat

Objective To investigate the mechanism of immune hyporesponsiveness induced by donor-antigen-unloaded recipient-derived immature dendritic cell (imDC) of liver grafts in rats.Methods Forty Sprague-Dawley rats (donor) and forty male Wistar rats (recipient) were randomly divided into 4 groups:control,cyclosporine A (CsA),mature DC (mDC),and imDC groups respectively,with 10 donor rats and 10 recipient rats in each group.Recipient rats in CsA group were treated with 10 mg·kg-1.d-1 CsA starting day 2 after the transplantation.Recipients in the mDC or imDC groups were given Wistar rat derived mDCs (1×106/rat) or imDCs (1×106/rat) via dorsal vein of the penis respectively 1 day before the transplantation.In each group,5 recipients were kept for determination of survival time and the other 5 rats were executed at day 10 after transplantation.Blood samples were collected for the measurement of serum alanine aminotransferase (ALT),total bilirubin (TBIL),interleulkin 2 (IL-2),interferon gamma (IFN-γ),IL-4,and IL-10 levels,liver tissue was harvested for HE staining and acute rejection evaluation.Expression levels of Fas-L/Fas in the grafts were detected by immunohistochemical staining; and Western blot was used to detect the expression level of Scurfin.Results The survival time of CsA and imDC groups was significantly longer than that of control and mDC groups (all P<0.05).The levels of serum ALT and TBIL in the control group (2072.20±217.93 IU/L and 147.42±22.02 umol/L) and mDC group (2117.00±285.13 IU/L and 141.58+20.82 μmol/L) were significantly higher than those in the CsA group (59.68±13.48 IU/L and 15.40±2.13 umol/L) or imDC group (50.80±19.63 IU/L and 14.44±3.49 umol/L) (all P<0.05).In the CsA and imDC groups,the levels of IL-2 (22.52±3.75 pg/mL and 22.12±3.90 pg/mL) and IFN-γ (309.20125.19 pg/mL and 321.00±21.64 pg/mL) were significantly lower,but the levels of IL-4 (297.60±25.07 pg/mL and 277.00±22.47 pg/mL) and IL-10 (1226.00+140.49 pg/mL and 1423.00±106.39 pg/mL) were higher than those of the control (IL-2:147.78±12.80 pg/mL,IFN-γ:1758.60±106.22 pg/mL,IL-4:17.40+4.77 pg/mL,IL-10:81.00± 9.47 pg/mL) and mDC groups (IL-2:142.34±9.29 pg/mL,IFN-γ:1835.OOi82.63 pg/mL,IL-4:15.60+ 3.96 pg/mL,IL-10:68.80±11.23 pg/mL) (all P<0.01).The expression level of Scurfin protein on CD4+CD25+ T cells of the imDC group (1.34±0.29) was significantly higher than that in the control (0.72±0.13),CsA (0.37±0.11),and mDC groups (0.78±0.17) (all P<0.05).Conclusion Donor-antigen-unloaded recipient-derived imDC is an effective treatment in inducing immune hyporesponsiveness through induction of T cell apoptosis,shift in Thl/Th2 balance,and proliferation of regulatory T cell.