RESUMO
BACKGROUND: Productivities of bioactive compounds in high-value herbs and medicinal plants are often compromised by uncontrollable environmental parameters. Recent advances in the development of plant factories with artificial lighting (PFAL) have led to improved qualitative and/or quantitative production of bioactive compounds in several medicinal plants. However, information concerning the effect of light qualities on plant pharmaceutical properties is limited. The influence of three different light-emitting diode (LED) spectra on leaf fresh weight (FW), bioactive compound production and bioactivity of Artemisia annua L. against the malarial parasite Plasmodium falciparum NF54 was investigated. Correlation between the A. annua metabolites and antimalarial activity of light-treated plant extracts were also determined. RESULTS: Artemisia annua plants grown under white and blue spectra that intersected at 445 nm exhibited higher leaf FW and increased amounts of artemisinin and artemisinic acid, with enhanced production of several terpenoids displaying a variety of pharmacological activities. Conversely, the red spectrum led to diminished production of bioactive compounds and a distinct metabolite profile compared with other wavelengths. Crude extracts obtained from white and blue spectral treatments exhibited 2 times higher anti-Plasmodium falciparum activity than those subjected to the red treatment. Highest bioactivity was 4 times greater than those obtained from greenhouse-grown plants. Hierarchical cluster analysis (HCA) revealed a strong correlation between levels of several terpenoids and antimalarial activity, suggesting that these compounds might be involved in increasing antimalarial activity. CONCLUSIONS: Results demonstrated a strategy to overcome the limitation of A. annua cultivation in Bangkok, Thailand. A specific LED spectrum that operated in a PFAL system promoted the accumulation of some useful phytochemicals in A. annua, leading to increased antimalarial activity. Therefore, the application of PFAL with appropriate light spectra showed promise as an alternative method for industrial production of A. annua or other useful medicinal plants with minimal environmental influence.
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Antimaláricos/uso terapêutico , Artemisia annua/química , Artemisininas/uso terapêutico , Malária Falciparum/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Plasmodium falciparum/efeitos dos fármacos , Terpenos/química , Adaptação Ocular , Artemisininas/análise , Extratos Vegetais/análise , Plantas Medicinais/química , TailândiaRESUMO
BACKGROUND AND AIM: Thiopurines are often used in combination with mesalazine for the treatment of ulcerative colitis (UC). Mesalazine formulations are delivered to the digestive tract by various delivery systems and absorbed as 5-aminosalicylic acid (5-ASA). 5-ASA is known to inhibit thiopurine S-methyltransferase (TPMT) activity and to affect thiopurine metabolism. There have been no studies comparing TPMT inhibition by multimatrix mesalazine (MMX) with other formulations. We investigated the difference in TPMT inhibition by different mesalazine formulations and prospectively confirmed the clinical relevance. METHODS: Plasma concentrations of 5-ASA, N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA), and TPMT activities were measured in UC patients receiving various mesalazine formulations (time-dependent or pH-dependent mesalazine or MMX) as monotherapy. Patients already on both time-dependent or pH-dependent mesalazine and thiopurines switched their mesalazine to MMX, examining 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP) 0 and 8 weeks after switching. Clinical relapse after switching was also monitored for 24 weeks. RESULTS: Plasma 5-ASA and N-Ac-5-ASA levels were significantly higher in patients receiving time-dependent mesalazine (n = 12) compared with pH-dependent mesalazine (n = 12) and MMX (n = 15), accompanied by greater TPMT inhibition. Prospective switching from time-dependent mesalazine to MMX decreased 6-TGN levels, increased those of 6-MMP, and increased 6-MMP/6-TGN ratios. Furthermore, this resulted in significantly more relapses than switching from pH-dependent mesalazine to MMX. CONCLUSIONS: Time-dependent mesalazine has higher plasma 5-ASA and N-Ac-5-ASA levels and greater TPMT inhibition than MMX. Therefore, switching from time-dependent mesalazine to MMX may lead to an increase of 6-MMP/6-TGN, which may reduce the clinical effectiveness of thiopurines, warranting close monitoring after switch.
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Anti-Inflamatórios não Esteroides , Colite Ulcerativa , Mesalamina , Humanos , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Azatioprina/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Mercaptopurina/uso terapêutico , Mesalamina/farmacologia , Mesalamina/uso terapêutico , Metiltransferases , Estudos ProspectivosRESUMO
BACKGROUND AND AIM: The usefulness of second-generation colon capsule endoscopy (CCE2) in ulcerative colitis (UC), especially in clinically inactive patients, has been reported. Capsule Scoring of Ulcerative Colitis (CSUC) was developed as a severity index for UC. We aimed to determine whether CSUC is useful for predicting relapse during clinical remission. METHODS: Forty-one UC patients in clinical remission who underwent CCE2 were prospectively registered from April 2016 to August 2019. Patients' CSUC score was obtained; those with subsequent relapse were followed up retrospectively. The correlation of CSUC with white blood cell count, platelet count, albumin, C-reactive protein, fecal calprotectin and fecal lactoferrin levels, and fecal immunochemical test results was evaluated; their predictive values for future relapse were compared. RESULTS: The correlations of CSUC with white blood cell, platelet, albumin, C-reactive protein, fecal calprotectin, fecal immunochemical test, and fecal lactoferrin values were rs = 0.13, 0.27, -0.25, 0.15, 0.50, 0.43, and 0.50, respectively. CSUC was higher in 12 patients who relapsed within 1 year than in 29 patients who remained in clinical remission (2.83 ± 1.95 vs 0.72 ± 1.00, P < 0.01). Receiver operator characteristic curve analysis showed that CSUC ≥ 1 was a predictor of relapse (area under the curve of 0.82, sensitivity of 83.3%, specificity of 58.6%) and maybe superior to fecal biomarkers. In the univariate analysis, patients with CSUC of 0 had a lower relapse rate than those with CSUC of ⧠1 (P = 0.03, log-rank test). After analyzing patients who underwent CCE2 within 6 months after the successful induction treatment, results showed that those with CSUC of ≤ 1 remained in clinical remission for a year. CONCLUSION: CSUC predicts relapse within 1 year in UC patients in clinical remission, especially when used 6 months after induction treatment.
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Endoscopia por Cápsula/métodos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/patologia , Biomarcadores/análise , Biomarcadores/sangue , Contagem de Células Sanguíneas , Proteína C-Reativa , Colite Ulcerativa/terapia , Fezes/química , Feminino , Seguimentos , Humanos , Masculino , Valor Preditivo dos Testes , Recidiva , Indução de Remissão , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de TempoRESUMO
BACKGROUND: Developmental programming of chronic kidney disease (CKD) in young adults is linked to preterm birth and intrauterine growth restriction (IUGR). Which confers a higher risk of progression to chronic kidney damage in children with very low birth weight (VLBW; born weighing < 1500 g): prematurity or IUGR? METHODS: This is a national historical cohort study of children with VLBW cared for in perinatal medical centers in Japan. Predictive factors included three latent variables (prematurity, IUGR, stress during neonatal period) and eight observed variables (gestational age, birth weight Z-score, maternal age, duration of treatment with antibiotics and diuretics, maternal smoking, late-onset circulatory collapse, kidney dysfunction) during the perinatal period. The primary endpoint was estimated glomerular filtration rate (eGFR) at age ≥ 3 years. A structural equation model was used to examine the pathologic constitution. RESULTS: The 446 children with VLBW included 253 boys and 193 girls, of mean age 5.8 ± 2.6 years and mean eGFR 111.7 ml/min/1.73 m2 at last encounter. Pathway analyses showed intrauterine malnutrition (ß = 0.85) contributed more to chronic kidney damage than stress during the neonatal period (ß = - 0.19) and prematurity (ß = 0.12), and kidney dysfunction and late-onset circulatory collapse were important observed variables in stress during the neonatal period. CONCLUSIONS: IUGR was more harmful to future kidneys of VLBW neonates. Neonatal kidney dysfunction and late-onset circulatory collapse were important risk factors for subsequent CKD development. This emphasizes the need for obstetricians to monitor for fetal growth restriction and neonatologists to minimize neonatal stress to prevent CKD in later life.
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Doenças do Prematuro , Recém-Nascido de muito Baixo Peso , Nascimento Prematuro , Insuficiência Renal Crônica , Peso ao Nascer , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Retardo do Crescimento Fetal/epidemiologia , Idade Gestacional , Humanos , Recém-Nascido , Japão , Masculino , Gravidez , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Fatores de RiscoRESUMO
Anti-tumor necrosis factor-α (TNF-α) is a principal treatment for Crohn's disease (CD). However, it increases the susceptibility to tuberculosis (TB) infection, and therefore, screening examination prior to treatment initiation is crucial. Here, we report the case of a patient with CD who developed pulmonary TB following anti-TNF-α therapy, despite negative screening. A 19-year-old female who had no history of TB or had traveled to TB-endemic regions was diagnosed with CD. After negative TB screening with chest X-ray and interferon-gamma release assay, the patient was initiated on oral prednisolone and pH-dependent mesalazine. The treatment was changed to infliximab (IFX) because of the inadequate response observed to prednisolone;however, she developed pulmonary TB only 10 weeks after the initiation of IFX. The standard short-course anti-TB regimen was initiated to treat pulmonary TB, whereas IFX was discontinued and replaced with budesonide. Our case suggests that the risk of developing TB should not be excluded, despite the initial negative TB screening, particularly when a patient develops respiratory symptoms during anti-TNF-α therapy.
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Doença de Crohn/terapia , Fármacos Gastrointestinais/uso terapêutico , Infliximab/uso terapêutico , Tuberculose Pulmonar/diagnóstico , Adulto , Anticorpos Monoclonais , Feminino , Humanos , Fator de Necrose Tumoral alfa/metabolismo , Adulto JovemRESUMO
BackgroundCongenital anomalies of the kidney and urinary tract (CAKUT) are the most prevalent etiologies of pediatric chronic kidney disease (CKD). However, no robust mass screening methods have been developed to detect patients with CAKUT, making early intervention to prevent progressive renal failure challenging.MethodsWe applied tandem mass spectrometry (MS/MS) to measure the creatinine (Cr) value from dried blood spot (DBS) analysis, which has been used for newborn mass screening. Subsequently, we evaluated the correlation between DBS Cr measured by MS/MS and serum Cr measured by the conventional method in pediatric patients with CKD. Finally, DBS Cr was measured in 190 full-term, healthy newborns on days 4-6 after birth.ResultsWe established a system of MS/MS-based measurement of Cr from DBS. Measured DBS Cr in the pediatric patients showed a strong association with serum Cr (r=0.86; P<0.01). The median DBS Cr value in newborns was 0.222 (interquartile range: 0.189, 0.269) mg/dl. No significant correlations were found between DBS Cr values and body weight, Apgar score, gestational age, and sex in newborns.ConclusionWe successfully established a method for MS/MS-based measurement of Cr for newborn screening and determined normal reference values for full-term newborns.
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Creatinina/sangue , Teste em Amostras de Sangue Seco/métodos , Triagem Neonatal/métodos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida , Feminino , Humanos , Recém-Nascido , Masculino , Valores de Referência , Reprodutibilidade dos TestesRESUMO
BACKGROUND: The aim of this study was to examine the sensitivity and specificity of pyuria-based diagnosis of urinary tract infection (UTI) in urine collected by transurethral catheterization, and the reliability of diagnosis of pyuria in urine collected in a perineal bag. The gold standard for UTI diagnosis is significant colony counts of a single organism in urine obtained in a sterile manner. METHODS: We enrolled 301 patients who underwent medical examination at the present hospital for possible UTI between January 2005 and December 2009. We collected 438 urine samples by transurethral catheterization. We investigated the accuracy of pyuria-based diagnosis of UTI using transurethral catheterization urine specimens, and the reliability of diagnosis of pyuria using bag-collected urine specimens. RESULTS: The false-negative rate of UTI diagnosis based on pyuria in transurethral catheterization urine sediments was 9.0%; there was no significant difference in the false-negative rate of UTI diagnosis between boys and girls. Approximately 28% of pyuria-positive bag-collected urine specimens were pyuria negative on transurethral catheterization; this rate was significantly higher in girls than in boys (56.7% vs. 8.9%, P < 0.0001). CONCLUSIONS: The absence of pyuria in transurethral catheterization urine sediments does not rule out UTI. Pyuria in bag-collected urine specimens frequently consists of urine leukocytes from external genitalia as well as from the urinary tract.
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Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções Urinárias/diagnóstico , Adolescente , Criança , Pré-Escolar , Reações Falso-Negativas , Feminino , Infecções por Bactérias Gram-Negativas/urina , Infecções por Bactérias Gram-Positivas/urina , Humanos , Lactente , Recém-Nascido , Masculino , Piúria/diagnóstico , Piúria/urina , Estudos Retrospectivos , Sensibilidade e Especificidade , Cateterismo Urinário , Infecções Urinárias/urina , Adulto JovemRESUMO
The clinical and pathological features of human intestinal spirochetosis (HIS) are not well known. Here we report 55 patients with HIS who were diagnosed at our institution during the past 5 years. Seven patients presented with symptoms such as abdominal pain or diarrhea, while the others were incidentally diagnosed during screening colonoscopy. Most patients had non-specific endoscopic findings, including intestinal edema or erosion. The diagnosis of HIS was histologically confirmed via hematoxylin and eosin staining, periodic acid-Schiff staining, and/or immunohistochemistry using anti-Treponema pallidum antibody. Among the 55 patients, five were diagnosed with diseases other than HIS (amoebic colitis, three;ulcerative colitis, one). Sixteen patients were treated with either amoxicillin or metronidazole;only metronidazole proved to be effective. The clinical significance of asymptomatic HIS remains unknown. Some case reports suggest a risk for increased severity in patients with immunodeficiency and/or sexually transmitted diseases. Therefore, aggressive treatment for HIS should be considered, particularly in high-risk patients.
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Colite/patologia , Infecções por Spirochaetales/patologia , Biópsia , Colonoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Although renal inulin clearance (Cin) is the gold standard for evaluation of kidney function, it cannot be measured easily. Therefore, creatinine clearance (Ccr) is often used clinically to evaluate kidney function. Enzymatically measured Ccr was recently found to be much higher than Cin because of the tubular secretion of creatinine (Cr). This study compared three measures of renal clearance, inulin, 2-h Ccr, and 24-h Ccr, in children. METHODS: Kidney function was evaluated in 76 children (51 males and 25 females) aged 1 month to 18 years with chronic kidney disease (CKD) by three renal clearance methods at almost the same time. RESULTS: Correlations between each pair of three renal clearance measurements were determined. Approximate glomerular filtration rate (GFR) was equal to 62 % of 2-h Ccr or 76 % of 24-h Ccr. CONCLUSION: Cr secretion by renal tubules was approximately 50 % of the GFR. In this study, we indicate that the measurements of 2-h Ccr or 24-h Ccr do not show true GFR but we could infer approximate GFR from the values. The use of 2- or 24-h Ccr might contribute to the treatment of pediatric CKD patients.
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Creatinina , Taxa de Filtração Glomerular , Inulina/administração & dosagem , Rim/fisiopatologia , Anormalidades Urogenitais/diagnóstico , Refluxo Vesicoureteral/diagnóstico , Adolescente , Fatores Etários , Biomarcadores/sangue , Biomarcadores/urina , Criança , Pré-Escolar , Creatinina/sangue , Creatinina/urina , Feminino , Humanos , Lactente , Japão , Rim/metabolismo , Masculino , Modelos Biológicos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores de Tempo , Urinálise , Anormalidades Urogenitais/sangue , Anormalidades Urogenitais/fisiopatologia , Anormalidades Urogenitais/urina , Refluxo Vesicoureteral/sangue , Refluxo Vesicoureteral/fisiopatologia , Refluxo Vesicoureteral/urinaRESUMO
Stenosing ureteritis (SU), a rare complication of Henoch-Schönlein purpura (HSP), typically presents with severe symptoms. We report the cases of two HSP patients presenting with gross hematuria, blood clotting, and colicky flank pain, followed by purpura on the lower extremities. Early-stage ultrasonography indicated hydronephrosis, thickened renal pelvic mucous membrane, and ureteral dilatation (UD), suggesting HSP complicated with SU. After early SU treatment with prednisolone, kidney function, thickened renal pelvic mucous membrane, and UD progressively normalized and the pain gradually disappeared. Regular ultrasonography of HSP patients from the onset of gross hematuria can be useful to detect early SU and facilitate conservative therapy with prednisolone. Diagnosis of SU can be easily missed by assuming HSP nephritis, particularly owing to the non-specific symptoms. Common characteristics as well as treatment methods and prognosis of SU are given in the literature review.
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Vasculite por IgA/complicações , Prednisolona/uso terapêutico , Ureter/patologia , Obstrução Ureteral/etiologia , Criança , Pré-Escolar , Constrição Patológica , Humanos , Vasculite por IgA/tratamento farmacológico , Masculino , Ureter/diagnóstico por imagem , Obstrução Ureteral/tratamento farmacológicoRESUMO
BACKGROUND: Although urinary biochemical markers can be assessed by their ratio to urinary creatinine (U-Cr) concentration, reference values in adults may not be applicable to children because the amount of Cr excreted varies by body size. We therefore measured the relationship between age and the ratios of urinary ß-2-microglobulin (U-ß2MG), N-acetyl-ß-d-glucosaminidase (U-NAG), calcium (U-Ca) and protein (U-Pr) concentration to those of U-Cr in children. METHODS: Fifty-seven patients aged >1 year with benign familial hematuria (median age, 6.3 years) were divided into three age groups: 1-4, 5-9, and ≥10 years. Urinary biomarkers were assayed using actual values; ratios to actual U-Cr values; and our standardized metric, namely 100-fold the ratio of serum Cr to U-Cr concentration; and the relationship of each of these to age was determined. RESULTS: The ratios of U-ß2MG, U-NAG and U-Ca to Cr varied significantly by age, being higher in younger than in older children, but the actual and standardized values of each did not vary by age, nor did any measurement of U-Pr. CONCLUSIONS: The ratios of urinary markers of tubular function, including U-ß2MG, U-NAG and U-Ca, to Cr vary by age, being higher in younger children. In contrast, the ratios of urinary markers of glomerular filtration (such as U-Pr)to Cr do not vary by age, making them suitable for corrections relative to Cr.
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Acetilglucosaminidase/urina , Envelhecimento , Creatinina/urina , Hematúria/urina , Microglobulina beta-2/urina , Adolescente , Fatores Etários , Biomarcadores/urina , Criança , Pré-Escolar , Seguimentos , Humanos , LactenteRESUMO
BACKGROUND: This retrospective study was performed to assess the 3 year outcome of a unified protocol for childhood idiopathic nephrotic syndrome. METHODS: Cyclosporine A (CsA) or CsA plus mycophenolate mofetil (MMF) were used in patients without remission on high-dose steroid therapy. CsA was maintained at an area under the whole blood concentration-time curve up to 4 h after dose (AUC0-4 ) of 1500 and 2000 ng·h/mL in steroid-dependent nephrotic syndrome (SDNS) and steroid-resistant nephrotic syndrome (SRNS), respectively. Ninety-one children were enrolled in the study (SDNS, n = 64; SRNS, n = 18). Patients were divided into minimal change (MC) and focal segmental glomerulosclerosis (FSGS) groups. Three year outcome was evaluated using clinical severity defined as degree of dependence on immunosuppressive therapy for maintenance of remission. RESULTS: In the SDNS group, the numbers of MC and no biopsy were 51 and 13, respectively. No patient had FSGS. Twelve SRNS patients had FSGS and six had MC. In SDNS, 15/64 patients (23%) received no medication. CsA was effective as steroid-sparing agent in 31/38 patients (82%). MMF was effective in all eight patients for whom CsA was unsuccessful. Remission rate in the SRNS group was 14/18 (78%; eight with CsA, and six with a combination of CsA + MMF). Five of the 14 SRNS remission patients received methylprednisolone pulse therapy. Four were resistant to therapy, and had impaired renal function. The clinical severity of MC and FSGS overlapped. CONCLUSIONS: Treatment with CsA and combination of CsA plus MMF was useful for SDNS and for remission induction in SRNS.
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Ciclosporina/administração & dosagem , Glucocorticoides/administração & dosagem , Ácido Micofenólico/administração & dosagem , Síndrome Nefrótica/tratamento farmacológico , Pré-Escolar , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Imunossupressores/administração & dosagem , Masculino , Indução de Remissão , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
A 19-year-old Japanese woman had been diagnosed with diabetes at the age of 9 years. She had a strong family history of diabetes, and genetic screening showed she had maturity-onset diabetes of the young type 3 (MODY3). Ultrasonography of the liver and magnetic resonance imaging showed multiple nodules consistent with hepatocellular adenoma (HA). Biopsy of the liver tumors revealed hepatocyte nuclear factor (HNF) 1α-inactivated HA. HA is known as a MODY3-related disease due to mutations in HNF1α. We present the first report of HA associated with MODY3 in Japan.
Assuntos
Adenoma de Células Hepáticas/metabolismo , Diabetes Mellitus Tipo 2/complicações , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Neoplasias Hepáticas/metabolismo , Adenoma de Células Hepáticas/complicações , Adenoma de Células Hepáticas/genética , Feminino , Fator 1-alfa Nuclear de Hepatócito/genética , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/genética , Mutação , Linhagem , Adulto JovemRESUMO
'Niigata S3' is a new strawberry (Fragaria × ananassa Duch.) cultivar that is early flowering and possesses high soluble solid content and good coloration. It was selected from a cross between Kei812 (seed parent) and 'Asuka-Ruby' (pollen parent). The first harvest date of 'Niigata S3' was December 27, 34 days earlier than 'Echigohime' and 9 days earlier than 'Asuka-Ruby' (means of 2007 and 2008). The marketable yield of 'Niigata S3' was 85% of 'Echigohime', 107% of 'Asuka-Ruby', while the early yield was 145% of 'Echigohime', 85% of 'Asuka-Ruby' (based on 2007 and 2008 means). The shape of the fruit is long conical, and its skin color medium-red. The fruit skin hardness of 'Niigata S3' was 31.5 g/mm(2), which was harder than 'Echigohime', and its average soluble solid content was 11.4%, which was higher than the values for 'Echigohime' and 'Asuka-Ruby' (2008). Furthermore, 'Niigata S3' did not bear apical overripe fruit. This new cultivar is adaptable to the climatic conditions of Niigata, as well as other regions that experience low winter temperatures and insolation.
RESUMO
BACKGROUND AND AIM: We have reported that second-generation colon capsule endoscopy (CCE-2) might be feasible for assessing the severity of mucosal inflammation in ulcerative colitis (UC). However, because of the low rate (69%) of complete evaluation of the colon and owing to inadequate cleansing. We believe that the method of bowel preparation could be improved by reducing volume. In the present study, we attempted to improve the colon-cleansing regimen in order to optimize the usefulness of CCE-2 in the management of UC patients. METHODS: Twenty patients with histologically confirmed UC were enrolled. Patients took a maximum 2.2 L lavage solution (polyethylene glycol solution and magnesium citrate) in two or three divided doses. To assess the effectiveness of the modified bowel preparation regimen, we evaluated the rate of total colonobservation, the effectiveness of bowel cleansing, andinterobserver agreement in assessing UC disease activity. We used a four-point grading scale (poor, fair, good, and excellent) for evaluating the quality of bowel cleansing. Matts' endoscopic score was used to evaluate disease activity. RESULTS: The rate of total colon observation was 85%, and 15 patients (75%) excreted the CCE-2 within 8 h. The proportion of excellent plus good cleansing was approximately 60%. There was a substantial interobserver agreement (κ = 0.777) in assessment of overall cleansing, which was still substantial at the fair cleansing level (κ = 0.700). CONCLUSION: Using CCE-2, the modified bowel preparation regimen, with reduced volume has the potential to succeed in the evaluation of mucosal severity in UC.
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Endoscopia por Cápsula/métodos , Catárticos/administração & dosagem , Colite Ulcerativa/diagnóstico , Polietilenoglicóis/administração & dosagem , Adulto , Idoso , Enema/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto JovemRESUMO
Patients with Crohn's disease are at higher risk of opportunistic infection, especially if treated with immunosuppressive therapy. Cytomegalovirus has been reported to cause ulcerated lesions mainly in the lower gastrointestinal tract of inflammatory bowel disease patients. We herein report a rare case of Crohn's disease complicated with cytomegalovirus esophagitis, which was difficult to distinguish from exacerbation of Crohn's disease. Diagnostic values of clinical course, blood tests, endoscopic and histological examinations are limited but the present case was therapeutically diagnosed by antiviral therapy in combination with histological evidence of cytomegalovirus.
Assuntos
Doença de Crohn , Infecções por Citomegalovirus , Esofagite , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/complicações , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/complicações , Esofagite/virologia , Esofagite/diagnóstico , Esofagite/tratamento farmacológico , Diagnóstico Diferencial , Antivirais/uso terapêutico , Masculino , Feminino , Adulto , Progressão da DoençaRESUMO
Background/Aims: Leucine-rich α-2-glycoprotein (LRG) is a new serum biomarker reflecting the disease activity of ulcerative colitis (UC), but its change during the acute phase has not been enough investigated. Methods: Patients with UC who initiated the induction therapy with steroid or advanced therapy (biologics or Janus kinase inhibitors) were prospectively enrolled. Associations of LRG, C-reactive protein (CRP) and fecal calprotectin (FC) at baseline, week 1, and week 8 with clinical remission at week 8 and subsequent endoscopic improvement within 1 year (Mayo endoscopic subscore of 0 or 1) were assessed. Results: A total of 143 patients with UC were included. LRG and CRP at week 1 were significantly lower in the clinical remission group than in the non-remission group (LRG, 20.6 µg/mL vs. 28.4 µg/mL, P< 0.001; CRP, 0.9 mg/dL vs. 2.3 mg/dL, P< 0.001) while FC demonstrated the difference between groups only at week 8. The area under the curves of week 1 LRG, CRP, and FC for week 8 clinical remission using the receiver operating characteristic curves analysis were 0.68, 0.71, and 0.57, respectively. Furthermore, LRG and CRP predicted subsequent endoscopic improvement as early as week 1, while FC was predictive only at week 8. Conclusions: LRG can be an early-phase biomarker predicting subsequent clinical and endoscopic response to induction therapy.
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BACKGROUND & AIMS: Acute pancreatitis is a common inflammatory disease mediated by damage to acinar cells and subsequent pancreatic inflammation with recruitment of leukocytes. We investigated the pathologic roles of innate immune cells, especially macrophages, in cerulein- and L-arginine-induced acute pancreatitis in mice. METHODS: Acute pancreatitis was induced by sequential peritoneal administration of cerulein to mice. We determined serum concentrations of amylase and lipase, pancreatic pathology, and features of infiltrating mononuclear cells. We performed parabiosis surgery to assess the hemodynamics of pancreatic macrophages. RESULTS: Almost all types of immune cells, except for CD11b(high)CD11c(-) cells, were detected in the pancreas of healthy mice. However, activated CD11b(high)CD11c(-) cells, including Gr-1(low) macrophages and Gr-1(high) cells (granulocytes and myeloid-derived suppressor cells), were detected in damaged pancreas after cerulein administration. CCL2(-/-) mice given cerulein injections developed significantly less severe pancreatitis, with less infiltration of CD11b(high)CD11c(-)Gr-1(low) macrophages, but comparable infiltration of myeloid-derived suppressor cells, compared with cerulein-injected wild-type mice. Parabiosis and bone marrow analyses of these mice revealed that the CD11b(high)CD11c(-)Gr-1(low) macrophages had moved out of the bone marrow. Furthermore, mice with macrophage-specific deletion of suppressor of cytokine signaling 3 given injections of cerulein developed less severe pancreatitis and Gr-1(low) macrophage produced less tumor necrosis factor-α than wild-type mice given cerulein, although the absolute number of CD11b(high)CD11c(-)Gr-1(low) macrophages was comparable between strains. Induction of acute pancreatitis by L-arginine required induction of macrophage migration by CCL2, via the receptor CCR2. CONCLUSIONS: Cerulein induction of pancreatitis in mice involves migration of CD11b(high)CD11c(-)Gr-1(low) macrophage from the bone marrow (mediated by CCL2 via CCR2) and suppressor of cytokine signaling 3-dependent activation of macrophage. These findings might lead to new therapeutic strategies for acute pancreatitis.
Assuntos
Ceruletídeo , Quimiocina CCL2/metabolismo , Quimiotaxia , Ativação de Macrófagos , Macrófagos/imunologia , Pâncreas/imunologia , Pancreatite/imunologia , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Doença Aguda , Animais , Arginina , Biomarcadores/metabolismo , Antígeno CD11b/metabolismo , Antígeno CD11c/metabolismo , Quimiocina CCL2/deficiência , Quimiocina CCL2/genética , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Modelos Animais de Doenças , Enzimas/sangue , Imunidade Inata , Depleção Linfocítica , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pâncreas/metabolismo , Pâncreas/patologia , Pâncreas/cirurgia , Pancreatite/induzido quimicamente , Pancreatite/metabolismo , Pancreatite/patologia , Pancreatite/prevenção & controle , Parabiose , Receptores CCR2/metabolismo , Receptores de Quimiocinas/metabolismo , Transdução de Sinais , Proteína 3 Supressora da Sinalização de CitocinasRESUMO
Pierson syndrome (OMIM 609049) is typically characterized by congenital nephritic syndrome and peculiar ocular anomalies with microcoria. It is caused by mutations in LAMB2, which encodes laminin ß2. Approximately 50 mutations of LAMB2 from approximately 40 unrelated families have been identified; however, most of them were from Western countries. Although three patients in Asia with mutations of LAMB2 have been reported, they were not typical cases. We report the first Japanese case of Pierson syndrome with proven causative LAMB2 mutations. She presented with congenital nephrotic syndrome and bilateral microcoria at birth, and developed end-stage renal disease at 2 months of age. This is the first report of a typical case from Asia. LAMB2 analysis by direct sequencing revealed the compound heterozygous mutations c.3974_3975insA (p.N1325KfsX1331, maternal, novel) in exon 25 and c.4519C>T (p.Q1507X, paternal) in exon 27. The phenotype due to LAMB2 mutations appears to be similar between different ethnic groups.
Assuntos
Anormalidades Múltiplas/genética , DNA/genética , Anormalidades do Olho/genética , Laminina/genética , Mutação , Síndrome Nefrótica/genética , Distúrbios Pupilares/genética , Anormalidades Múltiplas/metabolismo , Análise Mutacional de DNA , Anormalidades do Olho/metabolismo , Feminino , Humanos , Recém-Nascido , Japão , Laminina/metabolismo , Síndromes Miastênicas Congênitas , Síndrome Nefrótica/metabolismo , Fenótipo , Distúrbios Pupilares/metabolismoRESUMO
Introduction: A large proportion of small bowel lesions in Crohn's disease (CD) may exist beyond the reach of ileocolonoscopy and there is no gold standard imaging modality to screen them, suggesting the need for optimal biomarkers. We aimed to compare the usefulness of C-reactive protein (CRP), faecal calprotectin (FC), and leucine-rich alpha-2 glycoprotein (LRG) in determining small bowel lesions of CD. Methods: This was a cross-sectional observational study. CRP, FC, and LRG were prospectively measured in patients with quiescent CD who underwent imaging examinations (capsule or balloon-assisted endoscopy, magnetic resonance enterography, or intestinal ultrasound) selected by the physician in clinical practice. Mucosal healing (MH) of the small bowel was defined as a lack of ulcers. Patients with a CD activity index >150 and active colonic lesions were excluded. Results: A total of 65 patients (27, MH; 38, small bowel inflammation) were analysed. The area under the curve (AUC) of CRP, FC, and LRG was 0.74 (95% confidence interval: 0.61-0.87), 0.69 (0.52-0.81), and 0.77 (0.59-0.85), respectively. The AUC of FC and LRG in a subgroup of 61 patients with CRP <3 mg/L (26, MH; 32, small bowel inflammation) was 0.68 (0.50-0.81) and 0.74 (0.54-0.84), respectively. The cut-off of 16 µg/mL of LRG showed the highest positive predictive value of 1.00 with specificity of 1.00, while negative predictive value was highest (0.71) with sensitivity of 0.89 at the cut-off of 9 µg/mL. Conclusion: LRG can accurately detect and/or exclude the small bowel lesions with two cut-off values.