Comparison of the Plasma Metabolome Profiles Between the Internal Thoracic Artery and Ascending Aorta in Patients Undergoing Coronary Artery Bypass Graft Surgery Using Gas Chromatography Time-of-Flight Mass Spectrometry

BACKGROUND: The left internal thoracic artery (LITA) has been used as the first conduit of choice in coronary artery bypass grafting (CABG) because of excellent long-term patency and outcomes. However, no studies have examined substances other than nitric oxide that could be beneficial for the bypass conduit, native coronary artery or ischemic myocardium. This study was conducted to evaluate differences in metabolic profiles between the LITA and ascending aorta using gas chromatography-time of flight-mass spectrometry (GC-TOF-MS). METHODS: Twenty patients who underwent CABG using the LITA were prospectively enrolled. Plasma samples were collected simultaneously from the LITA and ascending aorta. GC-TOF-MS based untargeted metabolomic analyses were performed and a 2-step volcano plot analysis was used to identify distinguishable markers from two plasma metabolome profiles. Semi-quantitative and quantitative analyses were performed using GC-TOF-MS and enzyme-linked immunosorbent assay, respectively, after selecting target metabolites based on the metabolite set enrichment analysis. RESULTS: Initial volcano plot analysis demonstrated 5 possible markers among 851 peaks detected. The final analysis demonstrated that the L-cysteine peak was significantly higher in the LITA than in the ascending aorta (fold change = 1.86). The concentrations of intermediate metabolites such as L-cysteine, L-methionine and L-cystine in the ‘cysteine and methionine metabolism pathway' were significantly higher in the LITA than in the ascending aorta (2.0-, 1.4- and 1.2-fold, respectively). Quantitative analysis showed that the concentration of hydrogen sulfide (H2S) was significantly higher in the LITA. CONCLUSION: The plasma metabolome profiles of the LITA and ascending aorta were different, particularly higher plasma concentrations of L-cysteine and H2S in the LITA.

Thiol/disulfide status regulates the activity of thiol-containing kinases related to energy homeostasis in rat kidney

ABSTRACT Considering that thiol-containing enzymes like kinases are critical for several metabolic pathways and energy homeostasis, we investigated the effects of cystine dimethyl ester and/or cysteamine administration on kinases crucial for energy metabolism in the kidney of Wistar rats. Animals were injected twice a day with 1.6 µmol/g body weight cystine dimethyl ester and/or 0.26 µmol/g body weight cysteamine from the 16th to the 20th postpartum day and euthanized after 12 hours. Pyruvate kinase, adenylate kinase, creatine kinase activities and thiol/disulfide ratio were determined. Cystine dimethyl ester administration reduced thiol/disulfide ratio and inhibited the kinases activities. Cysteamine administration increased the thiol/disulfide ratio and co-administration with cystine dimethyl ester prevented the inhibition of the enzymes. Regression between the thiol/disulfide ratio, and the kinases activities were significant. These results suggest that redox status may regulate energy metabolism in the rat kidney. If thiol-containing enzymes inhibition and oxidative stress occur in patients with cystinosis, it is possible that lysosomal cystine depletion may not be the only beneficial effect of cysteamine administration, but also its antioxidant and thiol-protector effect.

Multicenter Evaluation on the Efficacy of N-Acetyl Cystine in Relieving the Symptoms of Laryngopharyngeal Reflux Disease

BACKGROUND AND OBJECTIVES: Laryngopharyngeal reflux disease (LPRD) is relatively common disease. N-acetyl cysteine (NAC) has both mucolytic and antioxidant effect, also may be beneficial in inflammatory airway diseases. The purpose of this study was to evaluate the efficacy and safety of inhaled NAC therapy in LPRD. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 525 LPRD patients at 12 medical centers. Finally 401 patients subjected to inhaled NAC therapy for 2 months were enrolled in the study. We analyzed the change of Reflux Symptom Index (RSI) and Reflux Finding Score (RFS) after use of NAC for 4 weeks and 8 weeks in addition to the patient's compliance of the treatment. RESULTS: The RSI score significantly decreased from 19.87±6.34 to 12.78±6.93 after 4 weeks and to 10.65±7.47 after 8 weeks. The RFS score also significantly decreased from 9.29±3.4 to 7.17±3.41 after 4 weeks and to 6.1±3.73 after 8 weeks (p<0.05). During the treatment periods, 42 patients (10.4%) reported to have 80 episodes of discomfort. Throat discomfort (33%) and nausea (28%) were most common complaints, but the duration of discomfort was usually less than 4 weeks. CONCLUSION: Inhaled NAC treatment is highly effective for the reduction of both subjective and objective findings in LPRD patients. This study will provide the evidence of new treatment option for patients with LPRD. However, further studies will be needs to assess the real effect of inhaled NAC therapy as a standard treatment regimen of LPRD.

Metionina+cistina digestível para juvenis de tambaqui / Digestible methionine+cystine for tambaqui juveniles

Avaliou-se o efeito dos níveis de metionina+cistina digestível para juvenis de tambaqui na fase inicial de desenvolvimento (3,03±0,06g) durante 45 dias. Foram utilizados 160 juvenis de tambaqui distribuídos em DIC, com cinco tratamentos (níveis de metionina+cistina digestível = 0,66; 0,73; 0,80; 0,87; 0,94%), quatro repetições e oito animais por unidade experimental. As dietas utilizadas foram isoproteicas (25%) e isoenergéticas (3200kcal.kg-1). Os resultados obtidos foram submetidos aos testes de homogeneidade, normalidade, à análise de variância e à análise de regressão. Os parâmetros físicos e químicos da água do sistema de recirculação ficaram dentro da faixa de tolerância para a espécie. Os níveis de metionina+cistina digestíveis avaliados não influenciaram (P>0,05) a sobrevivência, o índice hepatossomático, o índice de gordura visceral e o consumo de ração. Entretanto, ganho de peso e taxa de eficiência proteica apresentaram aumento linear (P<0,05) com aumento da metionina + cistina na ração. Verificou-se que os níveis de metionina + cistina para o tambaqui não foram completamente atendidos, sendo recomendada a realização de novos estudos.(AU)

This study aimed to determine digestible methionine+cystine requirement of tambaqui juveniles in the early stage of development (3.03 ± 0.06 g) lasting 45 days. 160 tambaqui juveniles were distributed into DIC, with five treatments (methionine + cystine = 0.66; 0.73; 0.80; 0.87; 0.94%), four replications and eight animals per experimental unit. The basal diets were isonitrogenous (25% crude protein) and isocaloric (3200kcal.kg-1). The results were submitted to the homogeneity test, normality test, analysis of variance, and regression analysis. The physical and chemical parameters of water from the water recirculation system were within those recommended for the species. Digestible methionine+cystine levels did not influence (P>0.05) the survival, hepatosomatic index, visceral fat index and feed intake. However, weight gain and protein efficiency ratio exhibit a linear increase (P<0.05) with increase in methionine and cystine in the feed. Our results showed that the methionine + cystine levels for tambaqui were not fully met, and new studies are recommended.(AU)

Genotype and Phenotype Analysis in Pediatric Patients with Cystinuria

Cystinuria is an inherited disorder characterized by defective renal reabsorption of cystine and dibasic amino acids leading to nephrolithiasis. This study was conducted to analyze the genotypes and phenotypes of pediatric patients with cystinuria. Eight children from Seoul National University Hospital and Asan Medical Center presenting with cystinuria from January 2003 to June 2016 were retrospectively analyzed. Mutational studies were performed by direct sequencing. Two of the 8 were male and 6 were female. The median ages at onset and diagnosis were 1.5 (range, 0.3–13.6) and 2.6 (range, 0.7–16.7) years, respectively. The median followed up was 7.7 (range, 3.4–14.0) years. Mutational analyses were performed in 7 patients and revealed biallelic SLC3A1 mutations (AA genotype) in 4 patients, a single heterozygous SLC3A1 mutation (A- genotype) in 1 patient, biallelic SLC7A9 mutations (BB genotype) in 1 patient, and a single heterozygous SLC7A9 mutation (B- genotype) in 1 patient. Two of the mutations were novel. No genotype-phenotype correlations were observed, except for earlier onset age in patients with non-AA genotypes than in patients with the AA genotype. All patients suffered from recurrent attacks of symptomatic nephrolithiasis, which lead to urologic interventions. At the last follow-up, 3 patients had a mild-to-moderate degree of renal dysfunction. This is the first study of genotypic and phenotypic analyses of patients with cystinuria in Korea.

Endocrine complications during and after adolescence in a patient with cystinosis

Cystinosis is a rare disease characterized by abnormal lysosomal cystine accumulation of cystine due to impaired lysosomal transport. We previously reported the first case of cystinosis in Korea in a 12-year-old boy with short stature, general weakness, and photophobia. The diagnosis was confirmed based on ophthalmic findings and biochemical analyses (serum leukocyte cystine measurement). Major endocrine manifestations at diagnosis included hypothyroidism, growth retardation, and hypogonadism. Despite oral cysteamine administration and renal replacement therapy, multiple complications including both endocrine and nonendocrine disorders developed during and after adolescence. In this report, we review the presenting features and factors related to the long-term complications in a patient with cystinosis.

Modelos de norma de reação para estudo das características de qualidade da carne de codornas de corte em função das razões (metionina + cistina): lisina da dieta / Reaction norm models for the study of meat quality of european quail in function of (methionine + cysteine): lysine diet ratio

Objetivou-se avaliar a sensibilidade dos valores genéticos para características de qualidade da carne em codornas de corte alimentadas com dietas contendo diferentes relações de (metionina + cistina): lisina, do nascimento aos 21 dias de idade, por meio de modelos de normas de reação. Utilizaram-se 9011 informações de qualidade de carne referentes a 1400 progênies de 80 reprodutores e 160 matrizes de duas linhas (LF1 e LF2). Para o ajuste dos modelos de regressão aleatória, foi usado o programa WOMBAT, considerando-se nas análises homogeneidade de variância residual. As codornas foram alimentadas do nascimento aos 21 dias de idade com dietas contendo as relações 0,61; 0,66; 0,71; 0,76 e 0,81 de (metionina + cistina): lisina, mantendo os níveis de proteína bruta de 26,12% e de energia em 2900 kcal EM/kg da dieta. Dos 22 aos 35 dias de idade, todas as codornas foram alimentadas com dieta contendo 22% de proteína bruta e 3050 kcal EM/kg da dieta. As estimativas da variância genética e da herdabilidade foram influenciadas pelo gradiente ambiental e pela linha, com mudanças nessas estimativas com o aumento do gradiente ambiental. Os valores genéticos das características de qualidade de carne referentes a cada uma das linhas se alteraram com o aumento das relações de aminoácidos das dietas em razão das mudanças no ordenamento dos valores genéticos, evidenciando a existência da interação genótipo x nível de relação dos aminoácidos da dieta para características de qualidade de carne. Predições de valores genéticos de características de qualidade de carne com base em determinada relação de (metionina + cistina): lisina da dieta não são válidas para outras relações desses aminoácidos.

This study aimed to evaluate the sensitivity of breeding values for meat quality traits of European quails fed different (methionine + cystine): lysine ratio diets from hatch to 21 days of age, using reaction norm models. A total of 9011 meat quality records from 1400 progenies of 80 sires and 160 dams from two lines (LF1 and LF2) were used in the analyses considering homogeneity of residual variance. The quails from hatch to 21 days of age were fed diets containing 0.61, 0.66, 0.71, 0.76 and 0.81 (methionine + cystine): lysine ratios, 26.12% of crude protein and 2900 ME/kcal of diet. From 22 to 35 days of age all quail were fed a diet containing 22% of crude protein and 3050 kcal ME/kg of diet. The random regression model analyses was performed using the WOMBAT program considering homogeneity of residual variance. Genetic variance and heritability estimates were affected by the environment gradient of diet and line, increasing these estimates with the increase of the (methionine + cystine): lysine ratio of the diet. The breeding values changed with the increase of the environment gradient of the diet with changes in the rank of genetic breeding values characterizing the existence of genotype by environment interaction for meat quality traits. Predictions of meat quality trait breeding values based on a given (methionine + cystine): lysine ratio are not valid for other levels of the amino acid ratio.

Características de carcaça de codornas de corte EV1 alimentadas com diferentes níveis de metionina+cistina total / Carcass traits of EV1 quail strain fed different methionine+cystine level diets

O peso e o rendimento das carcaças de codornas de corte da linhagem EV1 foram avaliados no 35° dia de idade em delineamento experimental inteiramente ao acaso, com os tratamentos consistidos de um fatorial 2 x 6, ou seja, dois sexos e seis níveis de metionina+cistina totais (0,73; 0,79; 0,85; 0,91; 0,97 e 1,03%), quatro repetições e 12 aves por unidade experimental. Foram avaliados peso corporal, peso e rendimento de carcaça, peito, coxa, asas, vísceras comestíveis e gordura abdominal. Não houve efeito da interação sexo x nível de metionina das dietas para nenhuma das variáveis analisadas. Houve efeito quadrático dos níveis de metionina+cistina sobre peso corporal, carcaça, peito, coxa, asa e coração, com pontos de máximo em 0,93% para peso corporal, carcaça, peito e coxa; 0,90% para peso de asa e 0,92% para peso de coração. O peso de fígado aumentou de forma linear à medida que foram aumentados os níveis de metionina+cistina das dietas. Os níveis de metionina+cistina da dieta influenciaram de forma quadrática nos rendimentos de peito e asas, com pontos de máximo estimados para codornas alimentadas com dietas contendo 0,96% e 0,98% de metionina+cistina, respectivamente. O maior rendimento de moela foi obtido nas codornas alimentadas com 0,73% de metionina+cistina. O peso corporal de carcaça, peito, coxa, asa, fígado, moela e o rendimento de fígado nas fêmeas foram maiores que nos machos. A exigência de metionina+cistina para pesos de carcaça e peito é 0,93%, e para rendimento de peito 0,96%...

Carcass weight and yield of European quail strain EV1 were evaluated at 35 days of age in a completely randomized experimental design, with the treatments consisting of a 2 x 6 factorial combination, two sexes and six different methionine+cystine levels of diets (.73; .79; .85; .91; .97 and 1.03%), with four replicates and 12 quails per experimental unit. Body weight, weights and yields of carcass, breast, thigh, wing and, edible giblets and abdominal fat were recorded. Significant and quadratic effect of methionine+cystine level on body weight, weights of carcass, breast, thigh and heart were observed with estimated maximum of body weight and weights of carcass, breast and thigh for quails fed .93% methionine+cystine diets, .90% for wing weight and .92% for heart weight. Increasing and linear response of liver weight to methionine+cystine level of diet was estimated while breast and wing yields showed quadratic responses with estimated maximum for quails fed .96% and .98% methionine+cystine level diets. Higher gizzard yield was observed for quails fed .73% diets. Higher body weight, and weights of carcass, thigh, wing, liver, gizzard and liver yields were estimated for females. Methionine+cystine requirement for quail carcass and breast weights is .93% and for breast yield .96%...

Litiasis por cistina: Reporte de un caso / Cystine lithiasis: Case report

La cistinuria es una enfermedad genética cuya expresión clínica es la formación de cálculos en las vías urinarias. Si bien este tipo de litiasis es poco frecuente se caracteriza por un elevado número de recidivas. En este trabajo, presentamos el caso de una paciente de 24 años con litiasis por cistina, en la que el diagnóstico se logró mediante el hallazgo de cristales de cistina en muestras de orina y la presencia de cistina como único componente de los cálculos expulsados espontáneamente en dos ocasiones y removidos por nefrolitotomía percutánea en una ocasión en un lapso de 6 meses. El tratamiento instaurado consistió en aumento de la ingesta de líquido, dieta con restricción de sodio y proteínas y administración de agentes alcalinizantes para aumentar el pH de la orina. Así mismo queremos mostrar la disponibilidad y el uso a nivel nacional de técnicas laboratoriales especializadas para el diagnóstico y seguimiento de pacientes con cistinuria.

Cystinuria is a genetic disease which clinical expression is the formation of stones in theurinary tract.Even though this kind of lithiasis is rare, it is characterized by a highrecurrence rate. In this work,we present the case of a 24-year-old female patient withcystine lithiasisin whom the diagnosis was made by detection of cystine crystals in urinesamples and the presence of cystine as the only component of kidney stonesspontaneously passed in two episodes and removed by percutaneous nephrolithotomyoncein a period of six months. The treatment measures established were increase of thefluid intake,restricted protein and sodium diet and administrationofalkaline agents toincreaseurinary pH. Wealsoshow the availability and use at national level of specializedlaboratory techniques for the diagnosis and follow-up of cystinuric patients.

Cuantificación de cistina en orina espontánea para la detección de cistinuria / Quantitation of urinary cystine for the detection of cystinuria / Determinagáo quantitativa de cistina urinaria para a detecgáo de cistinuria

La cistinuria es un error innato del metabolismo ocasionado por un defecto en el transporte renal de arginina, ornitina, lisina y cistina. La acumulación de este último aminoácido de baja solubilidad ocasiona episodios de urolitiasis característicos de la enfermedad. En el presente estudio se estandarizó un método espectrofotométrico confiable y de fácil ejecución para la determinación cuantitativa de cistina en orina espontánea. Se realizó el análisis en 184 muestras, correspondientes a 104 controles y 80 pacientes con urolitiasis. Con el objeto de validar el método y posteriormente establecer un rango de excreción normal en la población colombiana se evaluaron los siguientes parámetros: exactitud, precisión, linealidad y límite de detección. La técnica mostró coeficientes de variación intra e inter ensayos inferiores al 10% y una excelente linealidad, con un coeficiente r² entre concentraciones conocidas de cistina y absorbancia generada por el método de 0,998. Usando esta técnica se encontró un valor normal de excreción de 1,35 a 110,11 mg cistina/g creatinina. En cinco pacientes, de los 80 con nefrolitiasis, se hallaron valores elevados de cistina, compatibles con cistinuria. El método utilizado puede implementarse en cualquier laboratorio clínico para confirmar el diagnóstico de cistinuria e iniciar un tratamiento oportuno.

Cystinuria is an inborn error of metabolism, caused by a defect in renal tubular transport of the following aminoacids: arginine, ornithine, lysine and cystine. Accumulation of the latter poorly soluble aminoacid leads to the development of kidney stones, characteristic of the disease. In this study, an easy and dependable spectrophotometric method for the quantitative determination of urinary cystine was standardized. The analysis was performed on 184 samples from 104 controls and 80 patients with kidney stones. In order to validate the method and later establish a range of normal urinary cystine excretion in the Colombian population, the following parameters were evaluated: Accuracy, precision, linearity and lower limit of detection. The technique showed intra and intei assay coefficients of variation below 10%, and excellent linearity, with an R square (r²) coefficient between known cystine concentrations and absorbance generated by the method at 0.998. Using this technique, a normal urinary cystine excretion range of 1.35-110.11 mg cystine/g creatinine was found. Among the 80 patients with kidney stones, elevated urinary cystine levels were found in 5 of them, compatible with the presence of cystinuria. This method can be implemented in any clinical laboratory to confirm the diagnosis of cystinuria and provide opportune treatment.

A cistinúria é um erro inato do metabolismo, causado por um defeito no transporte tubular renal de ar-ginina, ornitina, lisina e cistina. A acumulagáo deste último aminoácido, pouco solúvel, provoca episodios de urolitíase, característicos da doenga. No presente estudo, foi padronizado um método espectrofotomé-trico confiável e de fácil execugáo para a determinagáo quantitativa de cistina em urina espontánea. A análise foi realizada em 184 amostras de 104 controles e 80 pacientes com urolitíase. A fim de validar o método e, posteriormente, estabelecer um intervalo de excregao normal na populagao colombiana, foram avaliados os seguintes parámetros: exatidáo, precisáo, linearidade e limite inferior de detecgáo. O método mostrou coeficientes de variagáo intra e inter ensaios inferiores a 10%, e excelente linearidade, com um coeficiente R quadrado (r²) entre concentragoes conhecidas de cistina e absorváncia gerada pelo método de 0,998. Com esta técnica, foi encontrado um valor normal de excregáo de 1,35-110,11 mg cistina/g de creatinina. Entre os 80 pacientes com urolitíase, foram encontrados níveis elevados de cistina em cinco deles, compatíveis com a presenga de cistinúria. Este método pode ser implementado em qualquer laboratorio clínico para confirmar o diagnóstico de cistinúria e proporcionar um tratamento oportuno.

Urinary cystine calculi and detection of polymorphism in the SLC3A1 gene in Sudanese children

To investigate polymorphism in exon 8 of the SLC3A1 gene in children with urinary cystine calculi in Khartoum. A semi-quantitative chemical method was used to analyse 175 urinary calculi removed surgically from paediatric patients at Soba Teaching Hospital in Khartoum between October 2005 and May 2009. DNA was extracted with phenol chloroform isoamyl alcohol, and exon 8 of the SLC3A1 gene was amplified in a thermocycler and sequenced with an AB3130 genetic autoanalyser. Of the 175 stones, 10 were cystine calculi [5.7%]. The sex ratio of the patients was 2.3:1 [boys to girls], and the mean age at cystine stone onset was 31.1 +/- 28.2 months [range, 3-125 months]. Of the 10 patients, 8 had a positive family history of calculi formation, 4 had bilateral calculi, 3 had both renal and urinary bladder calculi, and 2 had obstructive acute renal failure. All patients required more than one surgical operation. One patient had a missense mutation M467K in exon 8 of the SLC3A1 gene. The prevalence of cystine calculi among urinary calculi in Sudanese children was 5.7%. A family history was found in 80% of children. A mutation [M467T] was identified at exon 8 of the SLC3A1 gene in one child

Plasma amino acid profiling of "same symptom for different disease" in Uyghur medicine based on high-performance liquid chromatography / 中南大学学报(医学版)

OBJECTIVE@#To determine the plasma amino acid metabolism of "same symptom for different diseases" in different cancer patients in Uyghur medicine.@*METHODS@#Plasma amino acid concentration was tested by high-performance liquid chromatography (HPLC) in cancer patients with different symptom, and the spectral profiles were subjected to a t-test for statistical significance.@*RESULTS@#Compared with the healthy group, lung cancer, cervical cancer, breast cancer and gastric cancer patients with abnormal Savda had lower concentration of plasma amino acids except some amino acids. Lung cancer patients with abnormal Savda had higher concentration of plasma phenylalanine, serine, cystine, valine, isoleucine, leucine and aspartic acid than Unsavda patients (P<0.05). Cervical cancer patients with abnormal Savda had low concentration of plasma arginine, but higher concentration of plasma cystine than Unsavda patients (P<0.05). Breast cancer patients with abnormal Savda had higher concentration of plasma leucine, serine, taurine, cystine, tyrosine, valine, isoleucine and asparagine than Unsavda patients (P<0.05). Gastric cancer patients with abnormal Savda had high concentration of plasma cystine but lower concentration of plasma phenylalanine, threonine and arginine than Unsavda patients (P<0.05).@*CONCLUSION@#Different tumor patients with abnormal Savda have common characteristics and significant differences.

Medical and Dietary Therapy for Kidney Stone Prevention

The prevalence of kidney stone disease is increasing, and newer research is finding that stones are associated with several serious morbidities. These facts suggest that emphasis needs to be placed not only on stone treatment but also stone prevention. However, there is a relative dearth of information on dietary and medical therapies to treat and avoid nephrolithiasis. In addition, studies have shown that there are many misconceptions among both the general community and physicians about how stones should be managed. This article is meant to serve as a review of the current literature on dietary and drug therapies for stone prevention.

Multimodal Treatments of Cystine Stones: An Observational, Retrospective Single-Center Analysis of 14 Cases

PURPOSE: To document the experiences of a single institution in evaluating the clinical courses and treatment outcomes of patients with cystine stones. MATERIALS AND METHODS: The clinical data of 14 patients with cystine stones who were treated at our institution from March 1994 to July 2012 were reviewed. These data included age at first visit, gender, family history, body mass index, presence of a single kidney, stone locations, stone burden, routine urinalysis, and culture. In addition, we also analyzed data on surgery, shock wave lithotripsy, medical treatment, stone recurrence or regrowth, and overall treatment success rates. RESULTS: The mean age of our patients at their first visit was 19.6+/-5.0 years, and eight patients were males. The median stone burden and mean urine pH before each surgery were 6.5 cm2 and 6.5+/-0.9, respectively. Two patients had a family history of cystine stones. Patients underwent surgery an average of 2.7 times. The median interval between surgeries was 27.3 months, and 1 open surgery, 12 percutaneous nephrolithotomies, and 25 ureterorenoscopies were performed. Potassium citrate or sodium bicarbonate was used in nine cases. D-Penicillamine was continuously used in three patients. Patients had an average incidence of 3.2 recurrences or regrowth of stones during the median follow-up period of 60.5 months. CONCLUSIONS: Patients with cystine stones have high recurrence or regrowth rates and relatively large stone burdens. Adequate treatment schedules must therefore be established in these cases to prevent possible deterioration of renal function.

Pulmonary Thromboembolism Caused by PROS1 Gene Mutation / 계명의대학술지

Pulmonary embolism (PE) is a serious clinical problem in patients with acquired risk factor such as cancer, immobilization, recent trauma and surgery. However PE may occur in hereditary thrombophilia like protein S deficiency which is caused by PROS1 gene mutation. The author reports a case of pulmonary embolism in a 33-year-old man with protein S deficiency and PROS1 gene mutation. Genetic analysis of the patient showed mutation 1063C→T in exon 10 of PROS1 gene, resulting in a substitution of arginine by cystine at position 355 (R355C).

Pediatric Urolithiasis: Our 22-year Experience at a Single Center

PURPOSE: Pediatric urolithiasis is uncommon in children but is a cause of significant morbidity and damage to the kidney. Although much information on adult urolithiasis is available in the literature, large studies on the pediatric population are still scarce. In this report, we review our experience with pediatric urolithiasis over 22 years at a tertiary referral center. METHOD: We retrospectively reviewed the records of children with newly diagnosed urolithiasis between January 1991 and May 2013. We assessed the age, sex, family history, initial symptoms, location of stones, underlying cause, stone analysis, treatment, and recurrence among the patients. RESULTS: In total, 137 patients (96 male, 41 female) were assessed. The age range was 0-17 years (mean age, 6.0 years). Forty-three (31%) children were aged <1 year, and 37% (16/43) had a history of intensive care unit (ICU) admission. Thirteen patients (9.5%) had a family history of stones. The most common symptoms at presentation among the patients were gross hematuria (56/137, 41%) and flank or abdominal pain (46/137, 34%). The stones were located in the kidney (85/137, 62%), ureter (29/137, 21%), bladder (2/137, 1.4%), and multiple locations (20/137, 15 %). Congenital abnormalities of the genitourinary (G-U) tract, with or without metabolic abnormality, or urinary tract infection (UTI) was detected in 26 children (19%). Ninety-one patients (66%) underwent metabolic examination, and 38% of these patients exhibited an abnormality. UTI, with or without abnormalities of the G-U tract, or metabolic abnormality was detected in 26 children (19%). Of the 35 stones analyzed, the majority were calcium stones (20/35, 57%), followed by infected stones (5/35, 14%), uric acid stones (4/35, 11%), carbonate apatite stones (3/35, 7%), cystine stones (2/35, 6%), and phosphate stones (1/35, 3%). Five patients (4%) required open procedures, with or without non-open procedures, whereas 77 patients (56%) were managed conservatively; the remaining 55 patients (40%) received some other form of intervention. Eighteen patients (13%) had stone recurrence during the follow-up period. CONCLUSIONS: Pediatric urolithiasis is commonly associated with abnormalities of the G-U tract and/or metabolic disorders and/or UTI. Half of the patients will pass their stones spontaneously, and all the techniques of minimally invasive surgery are applicable in the treatment of children with stones. As the recurrence rates are high among this population, long-term follow-up is recommended and the complete clearance of stones is important.

A Case of Cystinuria with Multiple Renal Stones in an 8-month-old Girl

Cystinuria is an autosomal recessive disease characterized by impaired transport of cystine and dibasic amino acids in the proximal renal tubule, resulting in the formation of cystine stones. It is believed to account for about 1% of all kidney stones and up to 10% of pediatric stones. Here we report a case of cystinuria with multiple renal stones confirmed by genetic mutational analysis. An 8-month-old girl was admitted to AMC with persistent fever and multiple renal stones. A renal sonogram showed multiple stones at the right renal pelvis, right distal ureter, and left renal medullary portion. An approximately 1 cm renal stone was extracted spontaneously, and stone analysis revealed it to be composed entirely of cystine. Cystinuria was confirmed by increased urine dibasic amino acid levels, including cysteine, and genetic mutational analysis showed the patient to be a homozygote for the pathogenic c. 1820del (p.L607fs) of SLC3A1. Despite treatment with oral hydration and urinary alkalinization, and restricted intake of animal protein, the stones increased in size and number. The patient has since been treated with tiopronin.

Loss of blaVIM-2 and blaIMP-1 during the Storage of Gram-Negative Bacilli, Antimicrobial Susceptibility of the Gene-Lost Strain, and Location of the Gene in the Cell / 대한임상미생물학회지

BACKGROUND: Gram-negative bacilli can be stored in cystine tryptic agar (CTA) at room temperature for over 1 year, but we experienced a loss of imipenem resistance among VIM-2-producing isolates. The aims of this study were to determine the frequency of loss of IMP-1 and VIM-2 genes during storage in CTA at room temperature and to document any change in the MIC of antimicrobial agents and the location of the gene. METHODS: Bacteria were isolated from clinical specimens at Severance Hospital collected from 1995-2000. Modified Hodge and double disk synergy tests were performed for screening of MBL-production isolates, and blaIMP-1 and blaVIM-2 were detected by PCR. Loss of resistance was tested in CTA at room temperature. PFGE and hybridization using a blaVIM-2 probe were carried out to determine the location of the VIM-2 gene. RESULTS: When VIM-2- and IMP-1-producing strains of eight P. aeruginosa and two Acinetobacter spp. were stored in CTA at room temperature, some isolates lost imipenem resistance after 3 days and 90% lost resistance after 15 weeks. Loss of resistance genes resulted in a decrease of the MIC of imipenem from 32-128 mug/mL to 0.5-8 mug/mL for P. aeruginosa, and from 32 mug/mL to 0.25-4 mug/mL for Acinetobacter spp. Hybridization of I-CeuI and S1-digested and PFGE suggested that VIM-2 genes are located on approximately 50-100 kb or 400 kb plasmids. CONCLUSION: Isolates may lose resistance genes when stored in CTA at room temperature. Therefore, it is necessary for MBL-production tests including the Modified Hodge test and double disk synergy test and detection of MBL genes.

Quantidade de metionina+cistina digestível para poedeiras semipesadas de 75 a 91 semanas de idade / Nutritional requirement of digestible methionine + cystine for brown-egg laying hens from 75 to 91weeks of age

Determinaram-se as exigências nutricionais de metionina+cistina digestível para poedeiras de linhagem comercial no segundo ciclo de produção de 75 a 91 semanas de idade, utilizando-se 150 aves semipesadas em delineamento inteiramente ao acaso. Estas foram distribuídas em cinco tratamentos, seis repetições e cinco aves por unidade experimental, alimentadas com uma dieta basal contendo 2.859kcal/kg de energia metabolizável e 16,30% de proteína bruta, suplementada com 0,132; 0,173; 0,215; 0,256 e 0,298% de DL-metionina (98%), de forma a proporcionar 0,588; 0,628; 0,669; 0,709 e 0,750% de metionina+cistina digestível na dieta. A inclusão de metionina+cistina obedeceu, respectivamente, às proporções de 67, 72, 77, 81 e 86% com a lisina fixada em 0,872%. Avaliaram-se os consumos de ração e de metionina+cistina, a conversão alimentar por dúzia e por massa de ovos, a taxa de postura, o peso e a massa de ovos, a porcentagem dos componentes dos ovos e a qualidade interna dos ovos e o ganho de peso. A inclusão de metionina+cistina digestível nas quantidades indicadas não exerceu efeito (P>0,05) sobre as características de produção e qualidade interna e externa dos ovos. A exigência estimada foi de 0,588% de metionina+cistina digestível, correspondendo ao consumo de 654,73mg/ave/dia.

This work determined the nutritional requirements for methionine + cystine for commercial hens in the second production cycle from 75 to 91 weeks of age, using 150 brown-egg layer hens in a completely randomized design, distributed in five treatments, six replicates of five hens each and fed a basal diet containing 2859kcal/kg of metobolizable energy, 16.30% crude protein supplemented with 0.132, 0.173, 0.215, 0.256 and 0.298% DL-methionine (98%), in order to provide 0.588, 0.628, 0.669, 0.709 and 0.750% methionine + cystine in the diet. The inclusion of methionine + cystine followed, respectively, the proportions of 67, 72, 77, 81 and 86% with lysine fixed at 0.872%. The feed intake, methionine + cystine intake, feed conversion per dozen eggs and egg mass, percentage of the eggs, egg weight, egg mass, percentage of egg components and internal quality of eggs and weight gain were evaluated. The inclusion methionine + cystine in the amounts indicated had no effect (P> 0.05) on the production characteristics and internal and external quality of eggs. The requirement was estimated at 0.588% methionine + cystine intake corresponding to 654.73mg/hen/day.

Exigência de metionina + cistina para frangas de reposição na fase recria de 13 a 18 semanas de idade / Requirement of methionine plus cystine for egg pullets in the growing phase from 13 to 18 weeks old

Determinou-se a exigência de metionina + cistina para frangas de 13 a 18 semanas de idade e verificou-se seu efeito sobre a fase de postura. O experimento foi dividido em duas fases experimentais, recria e postura. Na fase de recria, 560 aves - 50% Lohmann LSL e 50% Lohmann Brown -, com 13 a 18 semanas de idade, foram distribuídas em delineamento inteiramente ao acaso, em esquema fatorial 5x2 (porcentagem de met+cis e linhagens), com quatro repetições e 14 aves por repetição. As porcentagens de met+cis totais estudadas foram 0,399; 0,469; 0,539; 0,609 e 0,679%. Ao atingirem 22 semanas de idade, 240 aves foram utilizadas para se avaliar o efeito residual das dietas oferecidas na fase de recria sobre o desempenho das aves, a produção e a qualidade de ovos. Ao se considerar a fase de produção, não se verificou efeito da inclusão de níveis de met+cis na ração, para ambas as linhagens. As exigências de metionina + cistina totais foram de 0,679% (0,611% de met+cis digestível) para aves leves e de 0,646% (0,581% de met+cis digestível) para aves semipesadas.

The methionine + cystine requirement was determined for pullets from 13 to 18 weeks of age and its effect was verified on the laying phase. The experiment was divided into two experimental phases. In the growing phase 560 birds (50% and 50% Lohmann LSL Lohmann Brown) at 13 to 18 weeks of age were distributed in a completely randomized factorial scheme 5x2 (methionine + cystine levels and lineages), with four replications and 14 birds per repetition. The levels of total methionine + cystine studied were 0.399, 0.469, 0.539, 0.609 and 0.679%. When they reached 22 weeks of age, 240 birds were used to assess the residual effects of the diets offered in the growing phase on performance of poultry, egg production and quality. Considering the production phase, there was no effect of the inclusion of methionine + cystine levels in the diet for both strains. The total methionine and cysteine was 0.679% (0.611% of digestible methionine + cystine) for light birds and 0.646% (0.581% methionine + cystine digestible) for brown-egg pullets.