Hyperammonemia in a Patient with Late-Onset Ornithine Carbamoyltransferase Deficiency

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.

Endothelial nitric oxide synthase gene polymorphisms [G894T] in diabetes mellitus in Egypt

Diabetic nephropathy [DN] is one of the major microvascular complications of diabetes. Genetic predisposition has been implicated in DN. The eNOS protein synthesizes nitric oxide constitutively via a reaction including the conversion of L-arginine to L-citrulline, which involves the transfer of five electrons provided by nicotinamide adenine dinucleotide phosphate The aim of this study is to evaluate the association of G894T polymorphisms of endothelial nitric oxide synthase [eNOS] gene with the development of diabetic nephropathy [DN] among Egyptian patients with type 1,2 diabetes mellitus in Egypt. Study subjects comprised 86 patients of type 2 diabetes with nephropathy,23 patients of type 1 diabetes with nephropathy and 46 patients of type 2 diabetes without nephropathy. G894T genotypes was determined by SSP- PCR analysis. Mutant T allele, GT and TT genotypes of G894TSNP had no significant frequencies in type 1.2 diabetic patients with nephropathy compared to those without nephropathy. These findings indicate that G894T polymorphism of eNOS gene may be not considered as genetic risk factors for DN among Egyptian type 1, 2 diabetic patients. T2DM: type 2 diabetes mellitus-DN: diabetic nephropathy eNOS: Endothelial nitric oxide synthase:- SNP: single nucleotide polymorphism- SSP-PCR: sequence specific primer- polymerase chain reaction

Marcadores de estrés oxidativo en aterogénesis inducida por hiperfibrinogenemia / Oxidative stress markers in atherogenesis induced by hyperfibrinogenemia

INTRODUCTION: We studied plasmatic TNF-alpha, nitric oxide (NO) and citrulline behaviors and probable morphological mitochondrial alterations in aortic smooth muscle cells, in rats with atherogenesis induced by hyperfibrinogenemia in: A) control, B) multiple injured for 30 days and C) multiple injured for 60 days. MATERIAL AND METHODS: Hyperfibrinogenemia induction: adrenaline injection (0,1 mg/rat/day). TNF-alpha (pg/dL) was determined by Elisa and NO (microM) and citrulline (mM) by spectrophotometry. Morphological mitochondrial alterations were studied by electronic microscopy. Variables were analized: ANOVA, r coefficient and chi2 test. RESULTS: We observed a significant increment of TNF-alpha in multiple injured for 30 days (B) (50.05 +/- 2.29) as well as in multiple injured for 60 days (C) (74.99 +/- 2.82) related to control (A) (33.01 +/- 1.49) (p<0.001 in both groups). Citrulline presented a significant increased in (B) (5.56 +/- 0.20) and (C) (6.84 +/- 0.13) when compared to (A) (4.41 +/- 0.23) (p<0.001 in both situations). Mean while NO biodisponibility diminished significantly in (B) (8.97 +/- 0.70) and in (C) (5.32 +/- 0.68) when compared to (A) (21.65 +/- 1.74) (p<0.001 in both situations). CONCLUSIONS: Hyperfibrinogenemia could modify the NO physiopathological pathway and produced morphological mitochondrial alterations in aortic smooth muscle cells, probably producing ischemic lesions in the vascular wall and altering the vasodilatation response.

Valor crítico da citrulina para as complicações do enxerto no transplante de intestino / Critical value of citrulline for complications of intestinal transplant graft

OBJETIVO: Analisar, numa ampla amostra, o valor crítico da citrulina que confirma a presença das principais complicações do enxerto: rejeição e infecção. MÉTODOS: Foram coletadas 2135 amostras de citrulina sérica, na forma de gota de sangue seca, de 57 doentes submetidos a transplante de intestino/multivisceral no Jackson Memorial Hospital na Universidade de Miami, de março de 2004 a abril de 2006. Todas as amostras são do pós-operatório três meses em diante, passada a conhecida curva de elevação da citrulina após a recuperação das lesões causadas pela isquemia e reperfusão do pós-transplante. RESULTADOS: Utilizando um valor limite menor que 13 µmoles/L, a sensibilidade da citrulina foi de 96,4 por cento para detectar rejeicão celular aguda (RCA) moderada ou grave. A especificidade para as complicações mais freqüentes, rejeição e infecção foi de 54 por cento-74 por cento nas crianças e 83 por cento-88 por cento nos adultos, e o valor preditivo negativo (VPN) foi > 99 por cento. CONCLUSÃO: A citrulina pode ser utilizada como método não-invasivo para avaliar a evolução do enxerto intestinal após três meses do TI. Os episódios de RCA moderado e grave podem ser afastados quando o valor da citrulina for maior que 13 µmoles/L devido ao alto valor preditivo negativo.

OBJECITIVE: A biochemical marker for detection of acute cellular rejection following small intestine transplantation has been sought. Citrulline, a non- protein amino acid synthesized mainly by functioning enterocytes, has been proposed. Trial sensitivity has been reportedly high but with low specificity. Thus, the goal was to determine, in a sufficiently large analysis, the significant value of citrulline level in the post-transplant setting, which would correlate with complications such as rejection and infection. METHODS: Since March, 2004 2,135 dried blood spot (DBS) citrulline samples were obtained from 57 small intestine transplant recipients three months or more after post-transplant, i.e., once the expected period of recovery in the citrulline levels had occurred. RESULTS: Using a <13 vs. > 13 µmoles/L cut off point, sensitivity of DBS citrulline for the detection of moderate or severe ACR was extremely high (96.4 percent). Furthermore, specificity estimates (given the absence of ACR and these particular infections), while controlling for time-to-DBS sample were reasonably high (54 percent-74 percent in children and 83 percent-88 percent in adults), and the negative predictive value (NPV) was >99 percent. CONCLUSION: Citrulline is a non-invasive marker to evaluate problems of the intestinal graft after three months post-transplant. Due to the high NPV, a moderate or severe ACR can be ruled out, based exclusively on knowledge of a high value for DBS citrulline.

Permanent intestinal failure.

CONTEXT: Intestinal failure (IF) requires the use of parenteral nutrition as long as it persists and may be in case of persistence an indication for intestinal transplantation. EVIDENCE ACQUISITION: Literature search was performed both electronically and manually. RESULTS AND CONCLUSIONS: Biological evaluation of IF is becoming possible with the use of plasma citrulline as a marker of intestinal mass. Short bowel syndrome (SBS) is the leading cause of intestinal failure in infants while few epidemiological data are available to date. Data on morbidity and mortality in pediatric patients with SBS are very limited while long-term outcome seems to be improving. Other causes of intestinal failure include neuro muscular intestinal disease and congenital disease of enterocyte development. The management of IF should include therapies adapted to each type and stage of IF based on a multidisciplinary approach, in centers involving pediatric surgery, pediatric gastroenterology, parenteral nutrition expertise, home parenteral nutrition program, and liver-intestinal transplantation experience. Timing for referral of patients in specialized centers remains a crucial issue. The main causes of IF are briefly reviewed emphasizing the medico-surgical strategy for prevention and care-provision, adapted to each type and stage of IF.

Anticuerpos anti-péptido citrulinado cíclico / Cyclic citrullinated peptide antibodies

The determination of anti-cyclic citrullinated peptide antibodies (anti-CCP) is an extremely useful laboratory test in the differential diagnosis of patients in which Rheumatoid Arthritis (RA) is suspected. Citrullination is an unspecific protein modification associated to inflammation. The production of antibodies directed against citrullinated antigens in the synovial membrane is, on the contrary, specific for RA, for which important associations between these and the pathogen of the disease have been described. This review focuses on the different characteristics that make this test routinely asked for in clinical practice: high specificity; high positive predictive value in undifferentiated arthritis; early manifestation, development prior to clinical disease, and its association with a more aggressive course of the disease.

Anticuerpos anti-péptido citrulinado cíclico en artritis reumatoide, artritis psoriática y otras enfermedades / Anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis and psoriatic arthritis

The anti-cyclic citrullinated peptide (Anti-CCP) antibodies are actually the markers of highly specific recognize for rheumatoid arthritis (RA). Its presence in RA has been associated with higher disease clinical activity characterize by greater loss of function and development of erosive illness with important radiological damage. Furthermore, its production is an early process in RA development and because that, their presence is predictive for disease development. But in spite of the fact its high specificity, in the last years they also has been detected in other arthropathies diseases like psoriatic arthritis (PsA). Even if the prevalence of Anti-CCP in PsA reach values greater than expected for a disease different of AR, doesn`t reach statistical value, but its presence in this illness, like in AR, could might considerer a marker of disease severity, with development of aggressive clinic characteristics, polyarticular predominance, erosion presence and associated with shared epitope allele. The existing information don´t allow defining if this patience will develop more aggressive illness or existing concomitance of two joint diseases. More detail studies are necessary to defined that.

Plasma reactive nitrogen intermediate levels in patients with clinically active rheumatoid arthritis.

We studied reactive nitrogen intermediate levels in 31 patients with active rheumatoid arthritis (RA) taking indomethacin and 20 healthy controls using nitrite and citrulline levels, measured by spectrophotometry, as markers. Twenty patients with RA were followed up after 4 and 8 wk of treatment with additional therapy in the form of methotrexate. Mean nitrite levels in 31 patients were 0.94 +/- 0.41 mumol/ml and 20 controls it was 1.18 +/- 0.99. After treatment with methotrexate for 4 and 8 wk the levels were 0.9 +/- 0.45 and 1.25 +/- 1.15 mumol/ml, respectively. Mean citrulline levels in all patients was 1.68 +/- 0.11 and controls was 1.39 +/- 0.6 mumol/ml. Following therapy with methotrexate for 4 and 8 wk the levels were 1.40 +/- 0.49 and 1.40 +/- 0.51 mumol/ml, respectively. It is possible that serum levels of these products may not reflect alterations in the synovial fluid levels. Alternatively, whatever lowering may have been achieved by the anti-inflammatory effect of the therapy may have been countered by drug derived free radicals.

Citrulinemia / Citrulinemia

Se describen los casos clínicos de tres pacientes con citrulinemia, que fue diagnosticada respectivamente a las edades de tres meses, siete días y siete meses. En todos la concentración sanguínea de amonio era anormalmente alta (>200ug por ciento) y las de citrulina en suero fueron de 353, 1.759, 289 nm/ml respectivamente. El tratamiento consistió en una dieta hipoproteica e hipercalórica, con suplementos de L-carnitina (100 mg x kg x día). L-arginina (70 a 120 mg x kg x día) y vitaminas. Las manifestaciones clínicas de la enfermedad son mas severas y precoces cuanto menor es la actividad residual de la rginina succínico sintetasa, cuya deficiencia es responsable del trastorno y que está practicamente ausente en la forma neonatal