A case of 46,XY complete gonadal dysgenesis with a novel missense variant in SRY.

Disorders of sex development (DSD) with mild external genital abnormalities may be diagnosed after puberty. Here, we report a case of 46,XY complete gonadal dysgenesis with a novel missense variant in sex-determining region Y (SRY), diagnosed after primary amenorrhea. A 15-yr-old patient presented to our gynecology department with a chief complaint of amenorrhea. The patient was diagnosed with a 46,XY karyotype, and SRY gene positivity. Gonadotropin levels were high, whereas testosterone levels were low. A pelvic magnetic resonance imaging (MRI) revealed a hypoplastic uterus; however, no gonads could be identified. Laparoscopy revealed bilateral streak gonads, fallopian tube-like structures, and the uterus. The gonads were removed based on the risk of gonadal malignancy. Comprehensive genetic analysis of DSD revealed a previously unreported SRY variant, c.271A>T, p.Ser91Cys, and in silico analysis predicted the variant to be pathogenic. The patient was diagnosed with 46,XY complete gonadal dysgenesis with a novel missense variant in SRY. The patient continued female hormone replacement therapy and experienced breast enlargement and cyclic menstruation. Determining the etiology of DSD can be difficult, causing anxiety in patients and their families. In addition to surgical scrutiny, genetic analysis is important to aid in diagnosis and reassure patients and their families.

Genetic ablation of p62/SQSTM1 demonstrates little effect on pancreatic ß-cell function under autophagy deficiency.

Autophagy is known to play an essential role in intracellular quality control through the degradation of damaged organelles and components. We previously demonstrated that ß-cell-specific autophagy deficient mice, which lack Atg7, exhibited impaired glucose tolerance, accompanied by the accumulation of sequestosome 1/p62 (hereafter referred to as p62). Whereas p62 has been reported to play essential roles in regulating cellular homeostasis in the liver and adipose tissue, we previously showed that ß-cell-specific p62 deficiency does not cause any apparent impairment in glucose metabolism. In the present study, we investigated the roles of p62 in ß cells under autophagy-deficient conditions, by simultaneously inactivating both Atg7 and p62 in a ß-cell specific manner. Whereas p62 accumulation was substantially reduced in the islets of Atg7 and p62 double-deficient mice, glucose tolerance and insulin secretion were comparable to Atg7 single-deficient mice. Taken together, these findings suggest that the p62 accumulation appears to have little effect on ß-cell function under conditions of autophagy inhibition.

A Japanese boy with double diagnoses of 2p15p16.1 microdeletion syndrome and RP2-associated retinal disorder.

2p15p16.1 microdeletion syndrome is a recently recognized congenital disorder characterized by developmental delay and dysmorphic features. RP2-associated retinal disorder (RP2-RD) is an X-linked inherited retinal disease with a childhood onset caused by a loss-of-function variant in the RP2 gene. Here, we describe a 14-year-old boy with double diagnoses of 2p15p16.1 microdeletion syndrome and RP2-RD. The recurrence risk of each condition and the indication for potential therapeutic options for RP2-RD are discussed.

Left atrial dysfunction and stiffness in pediatric and adult patients with Type 1 diabetes mellitus assessed with speckle tracking echocardiography.

BACKGROUND: Subclinical diastolic dysfunction in patients with Type 1 diabetes mellitus (T1DM) caused by myocardial injury due to diabetic cardiomyopathy leads to a high risk of death and heart failure. This myocardial injury extends not only to the left ventricle (LV) but also to the left atrium (LA). However, LA function in children and young adults with T1DM has not been extensively studied. OBJECTIVE: Therefore, the aim of this study was to assess LA dysfunction in pediatric and adult patients with T1DM using LA strain analysis with echocardiography. SUBJECTS: Fifty-three patients (median age: 23 [range: 5-41] years) with T1DM. METHODS: We divided the patients into three age groups (D1: 5-14 years, D2: 15-24 years, D3: 25-41 years); 53 age- and sex-matched controls were divided into three corresponding groups (C1, C2, and C3). LA and LV functions were evaluated using echocardiography. RESULTS: LA reservoir strain was lower in the D2 and D3 groups than in the C2 and C3 groups (P = 0.001, P = 0.004, respectively). LA conduit strain was lower in the D2 group than in the C2 group (P = 0.002). LA stiffness was significantly greater in the D3 group than in the C3 group (P < 0.001). CONCLUSIONS: In patients with T1DM, LA phasic function decreased in adolescents and young adults, and LA stiffness increased in adult patients aged >30 years. LA phasic function and LA stiffness can be potentially used as early markers for diastolic dysfunction.

Gallstone formation due to rapid weight loss through hyperthyroidism.

Background Cholesterol metabolism has dramatically changed under hyperthyroid status. However, a combination of hyperthyroidism and cholecystolithiasis is very rare. Case presentation We report a case of cholelithiasis accompanied by hyperthyroidism in a 13-year-old girl who had recently lost 13 kg of weight (from 53 to 40 kg) in 1 month without loss of appetite. Ultrasonography showed multiple hyperechoic areas with acoustic shadowing in the gallbladder. Thyroid function tests showed that her serum free triiodothyronine (T3) and thyroxine (T4) levels were elevated and the thyroid-stimulating hormone level was decreased. In addition, serum thyrotropin receptor antibody and thyroid-stimulating antibody were detected. The final diagnosis was cholelithiasis with Graves' disease. Thiamazole ingestion was started immediately after the diagnosis, and laparoscopic cholecystectomy was performed 33 days after hospitalization. Conclusions Massive and sudden weight loss could be a risk factor for gallstone formation in children. In addition, hyperthyroidism has the potential to promote cholelithiasis via cholesterol metabolism.

Establishment of a system for screening autophagic flux regulators using a modified fluorescent reporter and CRISPR/Cas9.

Autophagy is a mechanism of bulk protein degradation that plays an important role in regulating homeostasis in many organisms. Among several methods for evaluating its activity, a fluorescent reporter GFP-LC3-RFP-LC3ΔG, in which GFP-LC3 is cleaved by ATG4 following autophagic induction and degraded in lysosome, has been used for monitoring autophagic flux, which is the amount of lysosomal protein degradation. In this study, we modified this reporter by exchanging GFP for pHluorin, which is more sensitive to low pH, and RFP to mCherry, to construct pHluorin-LC3-mCherry reporter. Following starvation or mTOR inhibition, the increase of autophagic flux was detected by a decrease of the fluorescent ratio of pHluorin to mCherry; our reporter was also more sensitive to autophagy-inducing stimuli than the previous one. To establish monitoring cells for mouse genome-wide screening of regulators of autophagic flux based on CRISPR/Cas9 system, after evaluating knockout efficiency of clones of Cas9-expressing MEFs, we co-expressed our reporter and confirmed that autophagic flux was impaired in gRNA-mediated knockout of canonical autophagy genes. Finally, we performed genome-wide gRNA screening for genes inhibiting starvation-mediated autophagic flux and identified previously reported genes such as Atgs. Thus, we have successfully established a system for screening of genes regulating autophagic flux with our pHluorin-LC3-mCherry reporter in mice.

Present status of prophylactic thyroidectomy in pediatric multiple endocrine neoplasia 2: a nationwide survey in Japan 1997-2017.

Background In Japan, prophylactic thyroidectomy involves out-of-pocket expense. The American Thyroid Association (ATA) recommends prophylactic thyroidectomy for medullary thyroid carcinoma (MTC) during early childhood in patients with multiple endocrine neoplasia type 2 (MEN2). The ATA reports a high frequency of postoperative complications in childhood, which also influenced the delay of prophylactic thyroidectomy in Japan. Methods This retrospective study of multiple medical centers in Japan included individuals aged <20 years diagnosed with germline RET mutations between 1997 and 2017. The onset and onset possibility were defined based on confirmed lesions or calcitonin levels. The definition of risk and prophylactic thyroidectomy were based on the ATA 2015 revised guideline. Results Twenty-one patients with MEN2 were enrolled (highest risk, n = 5; high risk, n = 5; and moderate risk, n = 11). The cumulative incidence of the onset/onset possibility reached 50% at 5 and 8 years and 100% at 9 years and 17 years in high- and moderate-risk patients, respectively. Of 7 patients with MEN2A, 71% underwent prophylactic thyroidectomy. Only one 5-year-old patient (C634Y) had increased serum calcitonin level after prophylactic thyroidectomy in the MEN2A group. The only permanent complication, which did not occur in patients who underwent total thyroidectomy alone, was hypoparathyroidism (33% of patients). This permanent complication occurred with clinically developed MTC. No permanent postoperative complications occurred in patients aged 5-6 years. Conclusions Prophylactic thyroidectomy reduces recurrence and postoperative complications in pediatric patients with MEN2. Early thyroidectomy based on only calcitonin level could possibly reduce thyroidectomy delay.

In-Depth Insight Into the Mechanisms of Cardiac Dysfunction in Patients With Type 1 Diabetes Mellitus Using Layer-Specific Strain Analysis.

BACKGROUND: Although the subclinical left ventricular (LV) dysfunction caused by diabetes mellitus (DM) results in a high risk of death and heart failure, the details of cardiac dysfunction across a wide age range remain unclear. The aim of this study was to assess LV dysfunction in patients with type 1 DM (T1DM) using layer-specific strain analysis by echocardiography.Methods and Results:The 52 patients (median age: 23 [range: 5-40] years) with T1DM were divided into 3 age groups (D1: 5-14 years, D2: 15-24 years, D3: 25-40 years); 78 age- and sex-similar controls were divided into 3 corresponding groups (C1, C2, and C3). Layer-specific longitudinal strain (LS) and circumferential strain (CS) of the 3 myocardial layers (endocardium, midmyocardium, and epicardium) were determined using echocardiography. Strains did not decrease in D1. Epicardial and midmyocardial CS at the basal level and LS in all layers were decreased in D2 compared with C2. CS at the basal level and LS in all layers were lower in D3 than in C3. The strains correlated with the duration of T1DM and LV wall thickness. CONCLUSIONS: In patients with T1DM, longitudinal deformation in all layers and epicardial and midmyocardial circumferential deformation at the basal level decreased from the late teens, which correlated with the duration of the disease and LV hypertrophy.

Surgical management of hypospadias in cases with concomitant disorders of sex development.

INTRODUCTION: To review the surgical treatment of hypospadias (HP) associated with disorders of sex development (DSD). PATIENTS AND METHODS: HP cases were assessed for DSD by gross examination for atypical external genitalia, and assessment of hormone levels and karyotype. There were 58 HP cases with concomitant DSD treated between 1999 and 2017. DSD classification, type of HP, sex assignment, hormonal abnormality, surgical strategy, and post-urethroplasty complications (post-UPC) were reviewed. RESULTS: DSD were sex chromosome abnormalities (n = 4), 46,XY (n = 51), 46,XX (n = 1), and 47,XY + 21 (n = 2). HP was perineal: (n = 26), scrotal: (n = 16), penoscrotal: (n = 15), and midshaft: (n = 1); repair was primary (n = 6) or staged (n = 52). Mean age at final urethroplasty (UP) was 4.12 ± 0.21 years; all cases had soft tissue interposition at UP. At mean follow-up 5.16 ± 0.56 years after final UP, observed post-UPC (n = 8; 13.8%) were urethral stenosis (n = 3), urethral diverticulum (n = 2), urethrocutaneous fistula (n = 2), and curvature (n = 1). Mean onset of post-UPC was 1.24 ± 0.77 years (range 0.1-6.3). The second half of our cases (n = 29; treated 2015 ~) had significantly less post-UPC (0/29; 0%) than the first half (8/29; 27.6%) (p = 0.0075). CONCLUSIONS: Although UP for HP + DSD was formidably challenging, we achieved a significant decrease in post-UPC through a combination of surgical techniques and experience.

MIRAGE syndrome is a rare cause of 46,XY DSD born SGA without adrenal insufficiency.

BACKGROUND: MIRAGE syndrome, a congenital multisystem disorder due to pathogenic SAMD9 variants, describes a constellation of clinical features including 46,XY disorders of sex development (DSD), small for gestational age (SGA) and adrenal insufficiency (AI). It is poorly understood whether SAMD9 variants underlie 46,XY DSD patients born SGA (46,XY DSD SGA) without AI. This study aimed to define the frequency and phenotype of SAMD9 variants in 46,XY DSD SGA without AI. METHODS: Forty-nine Japanese patients with 46,XY DSD SGA (Quigley scale, 2 to 6; gestational age-matched birth weight percentile, <10) without history of AI were enrolled. The single coding exon of SAMD9 was PCR-amplified and sequenced for each patient. Pathogenicity of an identified variant was verified in vitro. Placenta tissues were obtained from the variant-carrying patient, as well as from another previously described patient, and were analyzed histologically. RESULTS: In one 46,XY DSD SGA patient, a novel heterozygous SAMD9 variant, p.Phe1017Val, was identified. Pathogenicity of the mutant was experimentally confirmed. In addition to DSD and SGA, the patient had neonatal thrombocytopenia, severe postnatal grow restriction, chronic diarrhea and susceptibility to infection, all features consistent with MIRAGE, leading to premature death at age 14 months. The patient did not have any manifestations or laboratory findings suggesting AI. Placenta tissues of the two variant-carrying patients were characterized by maldevelopment of distal villi without other findings of maternal underperfusion. CONCLUSIONS: MIRAGE syndrome is a rare cause of 46,XY DSD SGA without AI. This study exemplifies that AI is a common feature of MIRAGE syndrome but that the absence of AI should not rule out a diagnosis of the syndrome.

Staged segmental urethroplasty for scrotal/perineal hypospadias: a new concept.

PURPOSE: We report the efficacy of staged segmental urethroplasty (SSUP) versus non-staged urethroplasty (NSUP) for treating scrotal/perineal hypospadias (SPH). METHODS: Between 1997 and 2015, 29 SPH patients underwent UP (SSUP: n = 15; NSUP: n = 14). Incidences of urethrocutaneous fistula (UF), stenosis of the neourethra (SNU), diverticula formation, and residual chordee (RC) were compared. Differences were statistically significant if p < 0.05. RESULTS: The difference in mean age at NSUP (3.2 ± 1.3 years) and at the final stage of SSUP (5.5 ± 2.4 years) was significant (p < 0.05). Mean operative times for NSUP and SSUP (total for all stages) were not significantly different (231.5 ± 117.5 versus 272.5 ± 99.4 min); however, the incidence of postoperative complications was significantly less in SSUP (n = 1; UF) compared with NSUP (n = 6; 2 cases of UF, 3 cases of SNU, and 1 case of RC; (p < 0.05). Mean follow-up was significantly shorter in SSUP; 1.4 ± 1.2 years versus 7.0 ± 4.5 years in NSUP (p < 0.05). CONCLUSION: SSUP would appear to be effective for treating SPH because of a significantly lower incidence of UF, SNU and RC during the first postoperative year, the period when complications have been reported to arise most frequently.

Cytomegalovirus as a potential trigger for systemic lupus erythematosus: a case report.

BACKGROUND: The role of cytomegalovirus infection in triggering systemic lupus erythematosus remains a subject of debate. Here, we present a case of childhood systemic lupus erythematosus with concomitant cytomegalovirus infection, which sheds light on the relationship between these conditions and their treatment in pediatric patients. CASE PRESENTATION: A 12-year-old Japanese girl with no history of systemic illness was diagnosed with systemic lupus erythematosus and concomitant primary cytomegalovirus infection. Her anti-cytomegalovirus immunoglobulin G antibodies were elevated during diagnosis and treatment. Further, the patient's cytomegalovirus pp65 antigenemia level was slightly elevated (1 cell per 5 × 10(4) cells). Treatment included the administration of ganciclovir, prednisolone, methylprednisolone, and cyclophosphamide, none of which prompted adverse effects. The patient was in good condition at the most recent follow-up. CONCLUSION: Ganciclovir treatment is not completely safe, and there are no clinical guidelines regarding its use in patients with systemic lupus erythematosus triggered by cytomegalovirus infection. Our experience with this case suggests that the decision to administer ganciclovir treatment in pediatric cases should be guided by a variety of factors in addition to the cytomegalovirus antigenemia level. These factors include lymphopenia, renal biopsy results, and cytomegalovirus DNA levels detected by polymerase chain reaction. The details of our patient's presentation and treatment should prove illustrative to other clinicians who face similar cases.

Phenotypic Variability and Newly Identified Mutations of the IVD Gene in Japanese Patients with Isovaleric Acidemia.

Isovaleric acidemia (IVA) is an autosomal recessive inborn error affecting leucine metabolism. It is caused by a deficiency in isovaleryl-CoA dehydrogenase (IVD), a mitochondrial matrix enzyme that catalyzes the oxidation of isovaleryl-CoA to 3-methylcrotonyl-CoA. IVD is a FAD-containing enzyme, consisting of four identical subunits. Clinical features of IVA include poor feeding, vomiting, lethargy, developmental delay, metabolic acidosis, and a characteristic "sweaty foot" odor. IVA is one of the target disorders for newborn screening by tandem mass spectrometry (MS/MS). The human IVD gene is located on chromosome 15q. To date, over 50 disease-causing mutations have been reported worldwide. In this study, we searched for IVD mutations in five Japanese patients with IVA (neonatal type, two patients; chronic intermittent type, two patients; and mild biochemical type, one patient). The diagnosis of IVA was confirmed by urinary organic acid analysis using gas chromatography and mass spectrometry. All coding exons and the flanking introns in the IVD gene were amplified by PCR and were directly sequenced. We thus identified six hitherto unknown mutations (p.G94D, p.E116K, p.M167T, p.L243P, p.L246P, and c.696+1G>T) and four previously reported (p.R53P, p.R395C, p.Y403C, and p.E411K) pathogenic mutations. All patients were compound heterozygotes, and each mutation was identified in a single patient. Pathogenicity of newly identified mutations was validated using computational programs. Among them, the p.M167T is believed to influence FAD binding, as the position 167 is present in one of the FAD-binding sites. Our results have illustrated the heterogeneous mutation spectrum and clinical presentation of IVA in the Japanese patients.

A report of two novel NR5A1 mutation families: possible clinical phenotype of psychiatric symptoms of anxiety and/or depression.

OBJECTIVE: NR5A1 or steroidogenic factor 1 is a nuclear receptor that plays important roles in the hypothalamus-pituitary-steroidogenic axis. The clinical phenotype of most 46,XY mutation carriers includes disorders of sex development (DSD) without adrenal insufficiency, whereas 46,XX mutation carriers have phenotypes ranging from no symptoms to ovarian insufficiency. Although genetically engineered ventromedial hypothalamus-specific Nr5a1 knockout mice show anxiety behaviour, no psychiatric symptoms have been reported in human NR5A1 mutation carriers. We report clinical and molecular findings for individuals (from two families) with NR5A1 mutations, showing psychiatric symptoms. DESIGN AND METHODS: We screened for NR5A1 mutations in a cohort of 34 patients with 46,XY DSD using PCR-based sequencing. Psychiatric symptoms were assessed using mental health assessment tools and structured clinical interviews. Functional properties of detected mutant NR5A1s were studied in silico and in vitro, including three-dimensional (3D) mutation models, subcellular NR5A1 protein localization and transactivation assays. RESULTS: We found 2 (46,XY) patients with NR5A1 heterozygous novel mutations (p.D257fs and p.V424del), which were transmitted from their respective mothers. The patients' clinical findings indicated DSD without adrenal insufficiency. Both mothers showed psychiatric symptoms, including excessive anxiety and/or depression. The mother and grandmother of one patient had premature ovarian insufficiency. Functional studies showed altered 3D models of p.V424del and normal subcellular NR5A1 localization and impaired transcriptional activation without dominant-negative effects in both mutations. CONCLUSIONS: We found 2 (46,XX) NR5A1 mutation carriers with excessive anxiety and/or depression. These results suggest that excessive anxiety and/or depression are possible clinical phenotypes of 46,XX NR5A1 mutations.

Isolated growth hormone deficiency in two siblings because of paternal mosaicism for a mutation in the GH1 gene.

CONTEXT: Mutations in the GH1 gene have been identified in patients with isolated growth hormone deficiency (IGHD). Mutations causing aberrant splicing of exon 3 of GH1 that have been identified in IGHD are inherited in an autosomal dominant manner, whereas other mutations in GH1 that have been identified in IGHD are inherited in an autosomal recessive manner. OBJECTIVE: Two siblings born from nonconsanguineous healthy parents exhibited IGHD. To elucidate the cause, GH1 in all family members was analysed. RESULTS: Two novel mutations in GH1, a point mutation in intron 3 and a 16-bp deletion in exon 3, were identified by sequence analyses. The intronic mutation was present in both siblings and was predicted to cause aberrant splicing. The deletion was present in one of the siblings as well as the mother with normal stature and was predicted to cause rapid degradation of mRNA through nonsense-mediated mRNA decay. The point mutation was not identified in the parents' peripheral blood DNA; however, it was detected in the DNA extracted from the father's sperms. As a trace of the mutant allele was detected in the peripheral blood of the father using PCR-RFLP, the mutation is likely to have occurred de novo at an early developmental stage before differentiation of somatic cells and germline cells. CONCLUSIONS: This is the first report of mosaicism for a mutation in GH1 in a family with IGHD. It is clear that the intronic mutation plays a dominant role in the pathogenesis of IGHD in this family, as one of the siblings who had only the point mutation was affected. On the other hand, the other sibling was a compound heterozygote for the point mutation and the 16-bp deletion and it may be arguable whether IGHD in this patient should be regarded as autosomal dominant or recessive.

Pulse steroids as induction therapy for children with ulcerative colitis.

BACKGROUND: Corticosteroids therapy, classically the first-line treatment for ulcerative colitis (UC), often causes serious side-effects. Theoretically, pulse steroid therapy where high doses are given for a shorter period may have maximal beneficial effects and minimal side-effects as induction therapy for UC. We have therefore retrospectively compared induction therapy using pulse steroids with conventional steroid treatment for children and adolescents with moderate-to-severe UC. METHODS: We utilized conventional steroid treatment (prednisolone 1-1.5 mg/kg/day) as an induction treatment in 17 UC patients between 1985 and 2006. Alternatively we used a 3-day megadose pulse steroid therapy (methylprednisolone intravenously 20-30 mg/kg/day, max. 1000 mg/day) in 20 UC patients from 1993 to 2006. RESULTS: Pulse steroid therapy successfully induced rapid remission in UC patients with moderate-to-severe disease compared with conventional treatment (13.2 days vs 25.1 days; P < 0.05). The amelioration of Pediatric Ulcerative Colitis Activity Index score between before and 1 week after pulse steroid therapy was significantly more than that of conventional treatment (P < 0.01). No serious adverse effects were observed in the patients treated with pulse steroid therapy. However, the rate of the relapse episodes during the next 12 months after pulse steroid therapy was not significantly different from that after conventional treatment. CONCLUSION: These findings suggest that pulse steroid therapy is an option to be considered in children with moderate-to-severe UC.

Assessment of Growth Disturbance in Japanese Children with IBD.

In Japan, there is as yet no report on growth retardation in children with IBD. We therefore investigated the cause of growth retardation in Japanese children with IBD. We investigated the height, body weight, serum levels of albumin, IGF-I, CRP, and cytokines, and the amount of corticosteroid administered in children with Crohn's disease (CD, n = 15) and ulcerative colitis (UC, n = 18). Our results suggest that growth retardation is already present before the initial visit in children with CD, and chronic inflammation may be responsible this growth disturbance. Moreover, the amount of PSL used may contribute to growth retardation by decreasing the serum levels of IGF-I in children with IBD.

Prolonged Intracranial Hypertension after Recombinant Growth Hormone Therapy due to Impaired CSF Absorption.

We experienced a case of a Japanese boy who developed intractable idiopathic intracranial hypertension (IIH) during growth hormone (GH) treatment. At the age of 4 yr, the boy was diagnosed with idiopathic growth hormone deficiency, and recombinant human GH replacement was initiated. Nine months after initiation of the GH therapy, he began to complain of headache, but papilledema was not observed. His headache persisted thereafter, and right esotropia occurred 10 mo after the initiation of GH therapy, at which time papilledema was detected. No other neurological abnormalities were detected, and the findings of computed tomography and magnetic resonance imaging were normal. In a cerebrospinal fluid (CSF) examination, the pressure was markedly elevated to 450 mmH2O, but no other abnormality was recognized. Impaired CSF absorption was detected using the pressure-volume index technique. The CSF levels of GH and insulin-like growth factor I were not increased. GH therapy was withdrawn after it was suggested that the IIH was associated with the GH therapy, but the headache persisted. The intracranial hypertension did not respond to diuretics, and prednisolone was only transiently effective. Although the funduscopic findings were normalized, increased CSF pressure was still observed. For over 2 yr, repeated lumbar puncture was necessary to protect against visual defect. IIH is an uncommon adverse event during GH therapy, but it must be considered carefully.

Studies of anti-inflammatory effects of Rooibos tea in rats.

BACKGROUND: Rooibos tea is known to be caffeine free with abundant flavonoids. Aspalathin and nothofagin, the main flavonoids contained in Rooibos tea, have stronger anti-oxidative activity than other flavonoids. As oxidative stress can induce inflammation, the anti-inflammatory effects of Rooibos tea were investigated using a rat colitis model. METHODS: Seven-week-old Wister rats were divided into two groups: one group given Rooibos tea, and one given water. After four weeks of breeding, serum superoxide dismutase (SOD) levels were determined using the Electron Spin Resonance analysis. Urine 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations were also determined as reflections of DNA damage using enzyme-linked immunosorbent assay. Furthermore, rats were administrated dextran sodium sulfate (DSS), which is known to induce colitis in rodents, with or without Rooibos tea to evaluate its anti-inflammatory activity. Clinical symptoms, hemoglobin, serum iron and SOD levels were compared between the groups. RESULTS: There were no significant differences in bodyweight gain or laboratory data between the groups. The serum SOD levels were significantly increased, and urine 8-hydroxy-2'-deoxyguanosine levels were significantly decreased in the Rooibos group compared with the controls (P < 0.05 in each). After DSS administration, the serum SOD levels were significantly higher in the Rooibos group compared to the controls (P < 0.05). As a result, a decreased hemoglobin level, observed in the control group, was prevented in the Rooibos group after the DSS challenge. CONCLUSION: Rooibos tea may prevent DNA damage and inflammation by its anti-oxidative activity in vivo. As Rooibos tea is free from caffeine, routine intake may be safe and useful in reducing oxidative stress in children.