This study aimed to investigate the clinical effect of transplantation of CD133⁺ peripheral blood stem cells or umbilical cord mesenchymal stem cells via the hepatic artery in children with type II hyperammonemia and its possible action mechanism. Umbilical cord mesenchymal stem cells were obtained by collecting cord blood (100-150 mL) from healthy fetuses and separating stem cell suspension (5 mL) from the cord blood by hydroxyethyl starch sedimentation. CD133⁺ peripheral blood stem cells were obtained by mobilizing peripheral blood from the fathers of sick children using recombinant human granulocyte colony-stimulating factor for 5 days, collecting mononuclear cells (120 mL), and separating out CD133⁺ cells by sorting. With catheterization and percutaneous puncture, the obtained stem cells were slowly injected into the liver of sick children via the hepatic artery. The changes in clinical symptoms and laboratory indices such as blood ammonia, liver function, and arginine and citrulline concentrations were observed. After stem cell transplantation via the hepatic artery, the 6 children showed significantly decreased blood ammonia levels, and their blood ammonia levels slowly increased 1 to 2 weeks later, but remained below 100 μmol/L, and changes in glutamic-pyruvic transaminase levels were similar to blood ammonia. Plasma citrulline and arginine concentrations increased significantly after transplantation and the increase in citrulline level exceeded the increase in arginine level. An 8 months follow-up visit for one typical patient showed that the weight and height increased after transplantation and sleep was improved without night crying. The child could actively gaze at interesting objects instead of responding indifferently and started to say simple words. With regard to fine motor skills, the child could pinch things with the thumb and middle finger instead of displaying a lack of hand-eye coordination and progress was also made in gross motor skills. Gesell test showed that the child made progress for an average of 3.82 months in all areas. It was concluded that after stem cell transplantation, children with type II hyperammonemia have decreased blood ammonia levels, stable and improved liver function and steadily increased plasma citrulline and arginine concentrations. They display a progressive trend in such aspects as movement, language and environmental adaptability. It is hypothesized that stem cell transplantation via the hepatic artery partially or totally activates, or provides supplementary ornithine carbamoyl transferase, so that plasma citrulline and arginine concentrations increase and urea cycle disorder can be corrected to some extent.
AC133 Antigen ; Ammonia ; blood ; Antigens, CD ; analysis ; Arginine ; blood ; Citrulline ; blood ; Female ; Glycoproteins ; analysis ; Hepatic Artery ; Humans ; Hyperammonemia ; blood ; surgery ; Infant ; Male ; Peptides ; analysis ; Stem Cell Transplantation

OBJECTIVETo investigate the potential role of serum citrulline level in evaluating the intestinal absorptive area and capacity in patients with short bowel syndrome (SBS).

METHODSSerum citrulline concentration was determined using high performance liquid chromatography (HPLC) in SBS patients (n=22) and healthy controls (n=33). In SBS patients, the remnant small bowel lengths and diameters were measured by radiography, and their 5- hour urine D- xylose excretion and intestinal protein absorption were also determined. The correlationship of serum citrulline level with remnant small bowel length, surface area, protein and D- xylose absorption was analyzed. The 6 patients receiving intestinal rehabilitative therapy, serum citrulline level, protein and D- xylose absorption after therapy were also measured.

RESULTSSerum citrulline level of SBS patients was significantly lower than that of healthy controls [(5.94+/- 2.65) vs [(16.87 +/- 5.97) micromol/L, P < 0.01]. In SBS patients, serum citrulline was positively correlated with remnant small bowel length and surface area (r=0.82 and r=0.86 respectively). There was also a significant correlationship of serum citrulline level with 5- hour D- xylose excretion (r=0.56) and intestinal protein absorption (r=0.48). Serum citrulline, 5- hour D- xylose excretion and intestinal protein absorption were all significantly raised in patients after rehabilitative therapy, although no correlation of increasing percentage was found among above three parameters.

CONCLUSIONSSerum citrulline concentration is positively correlated with intestinal absorptive area and capacity in SBS patients. It is a potential marker for evaluating the severity of intestinal failure and the efficacy of rehabilitative therapy in short bowel patients.

Adolescent ; Adult ; Aged ; Case-Control Studies ; Citrulline ; blood ; Female ; Humans ; Intestine, Small ; metabolism ; Male ; Middle Aged ; Short Bowel Syndrome ; blood ; metabolism ; physiopathology ; Xylose ; metabolism ; Young Adult

OBJECTIVETo systematically evaluate the values of 4 serum markers in the diagnosis of rheumatoid arthritis (RA).

METHODSSerum samples were obtained from 278 RA patients and 510 control subjects and the levels of rheumatoid factor (RF), anticyclic citrullinated peptide antibody (CCP), antikeratin antibody (AKA), and glucose-6-phosphate isomerase (GPI) were detected using immune turbidimetry, ELISA, indirect immunofluorescence, and ELISA, respectively. The values of these 4 serum markers and their combinations in RA diagnosis were systemically assessed.

RESULTSIn RA diagnosis using one serum marker, two markers, and three or four markers, RF, RF+CCP, RF+CCP+GPI, respectively, had the highest sensitivity; CCP, CCP+AKA, and RF+CCP+AKA+GPI, respectively, had the highest specificity; CCP, CCP+GPI, and RF+CCP+AKA+GPI, respectively, had the highest positive predictive value; GPI, RF+CCP, and RF+CCP+GPI, respectively, had the highest negative predictive value; CCP, CCP+GPI, and RF+CCP+AKA+GPI, respectively, had the highest positive likely ratio; GPI, RF+CCP, and RF+CCP+GPI, respectively, had the lowest negative likely ratio.

CONCLUSIONCCP, RF+CCP, and RF+CCP+GPI are the most ideal for RA diagnosis using one, two, and three or more markers, respectively. CCP is the essential marker for RA diagnosis, and a combined detection of the serum makers can significantly improve the diagnostic accuracy.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Arthritis, Rheumatoid ; blood ; diagnosis ; Autoantibodies ; blood ; Biomarkers ; blood ; Case-Control Studies ; Citrulline ; immunology ; Female ; Glucose-6-Phosphate Isomerase ; blood ; Humans ; Keratins ; immunology ; Male ; Middle Aged ; Rheumatoid Factor ; blood ; Young Adult

Ornithine carbamoyltransferase (OTC) deficiency is a urea cycle disorder that causes the accumulation of ammonia, which can lead to encephalopathy. Adults presenting with hyperammonemia who are subsequently diagnosed with urea cycle disorders are rare. Herein, we report a case of a late-onset OTC deficient patient who was successfully treated with arginine, benzoate and hemodialysis. A 59-yr-old man was admitted to our hospital with progressive lethargy and confusion. Although hyperammonemia was suspected as the cause of the patient's mental changes, there was no evidence of chronic liver disease. A plasma amino acid and urine organic acid analysis revealed OTC deficiency. Despite the administration of a lactulose enema, the patient's serum ammonia level increased and he remained confused, leading us to initiate acute hemodialysis. After treatment with arginine, sodium benzoate and hemodialysis, the patient's serum ammonia level stabilized and his mental status returned to normal.
Age of Onset ; Ammonia/blood ; Arginine/therapeutic use ; Citrulline/blood ; Humans ; Hyperammonemia/*etiology ; Male ; Middle Aged ; Ornithine/blood ; Ornithine Carbamoyltransferase Deficiency Disease/complications/*diagnosis/drug therapy ; Pedigree ; Renal Dialysis ; Sodium Benzoate/therapeutic use

Filaggrin is expressed in the cornified layer of epidermis and known to be one of the antigenic targets in rheumatoid arthritis. Although the citrulline residue in filaggrin is thought to be an antigenic determinant recognized by autoantibodies, the diagnostic sensitivity of synthetic citrullinated peptide is variable. To investigate the implication of anti-filaggrin antibodies recognizing uncitrullinated filaggrin in rheumatoid arthritis, we assayed antibody titers using unmodified recombinant filaggrin in the sera from 73 patients with rheumatoid arthritis, 150 patients with other connective tissue diseases and 70 normal controls. We also performed the correlation analysis between antibody titers and the clinical variables in patients with rheumatoid arthritis. Titers of IgG anti-filaggrin antibodies were significantly higher in rheumatoid arthritis patients compared to normal controls (P=0.02), but not in patients with osteoarthritis, ankylosing spondylitis or systemic lupus erythematosus. IgG anti-filaggrin antibodies were more frequently found in patients with rheumatoid arthritis compared to normal controls (12.3% vs 1.4% respectively, P=0.04). An anti-filaggrin antibody titer was correlated with visual analogue scale of pain, tender joint count, Ritchie articular index or C-reactive protein, but not with anti-nuclear antibody or rheumatoid factor. These results suggest that anti-filaggrin antibody recognizes the uncitrullinated filaggrin as an antigen and its titer correlates with clinical parameters, explaining the variable sensitivity of anti-filaggrin antibody test.
Amino Acid Sequence ; Antibodies/*blood/*immunology ; Arthritis, Rheumatoid/blood/*diagnosis/*immunology ; Case-Control Studies ; Citrulline/*analysis ; Humans ; Intermediate Filament Proteins/*chemistry/*immunology/isolation & purification ; Molecular Sequence Data ; Research Support, Non-U.S. Gov't

Two clinical phenotypes for citrin deficiency (CD) have been reported. One is adult-onset citrullinemia type II (CTLN2) and another is neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). A child with CD and who had failure to thrive (FTT) and dyslipidemia as main clinical manifestations is reported here. Both the weight-and length-for-age at 18 months dropped below the 3rd percentile in the corresponding WHO anthropometry percentile charts, while blood biochemical analysis revealed dramatically increased triglyceride and total cholesterol, together with reduced HDL-cholesterol. Inquiries revealed his aversion to rice and fondness for fish since the age of one year, a peculiar habit which could not be corrected. Since the age of two years, the peculiar diet became more obvious, and slightly increased citrulline and threonine levels were detected on blood amino acid analysis. At the age of two years and five months he was suspected to have CD. Since then, he has been fed in accordance with his own food preferences, and FTT improved gradually, with weight-for-age, in particular, recovering beyond the 3rd percentile at three years of age, and dyslipidemia was also ameliorated gradually. SLC25A13 gene analysis revealed a homozygote of 851del4, and CD was thus confirmed. Diet survey at four years and seven months revealed a fondness for high-protein and low-carbohydrate foods, such as seafood, meat, eggs and milk. This child presented with FTT and dyslipidemia as main clinical manifestations and this was a novel CD phenotype different from NICCD and CTLN2.
Body Weight ; Calcium-Binding Proteins ; deficiency ; Cholestasis, Intrahepatic ; etiology ; Citrulline ; blood ; Dyslipidemias ; etiology ; Failure to Thrive ; etiology ; Humans ; Infant ; Lipids ; blood ; Male ; Mitochondrial Membrane Transport Proteins ; genetics ; Mutation ; Organic Anion Transporters ; deficiency ; Phenotype