Clinical, biochemical, and molecular insights into Cerebrotendinous Xanthomatosis: A nationwide study of 100 Turkish individuals.

OBJECTIVE: Cerebrotendinous xanthomatosis (CTX) is an inherited metabolic disorder characterized by progressive neurologic and extraneurologic findings. The aim of this retrospective, descriptive study was to explore the time of presentation and diagnosis, and to expand the phenotype and genotype of CTX, based on a nationwide and comprehensive series of patients in Turkey. METHODS: The demographic, clinical, biochemical and genotypic characteristics of the CTX patients were reviewed. Data on molecular analysis, age of onset and diagnosis, diagnostic delay, neurologic and extraneurologic symptomatology, results of plasma cholestanol levels, brain magnetic resonance imaging and electromyography at the time of diagnosis were reviewed. RESULTS: 100 confirmed CTX patients from 72 families were included. The mean age at diagnosis was 28.16 ± 14.28 years, and diagnostic delay was 18.39 ± 13.71 years. 36 patients were diagnosed in childhood. Frequency of intention tremor (p = 0.069), peripheral neuropathy (p = 0.234) and psychiatric manifestations (p = 0.396) did not differ between two groups, demonstrating the high rate in pediatric patients. Three adult patients showed a milder phenotype without neurologic involvement. Seven patients had normal plasma cholestanol levels despite neurological impairment. Sequencing of the CYP27A1 gene revealed 25 different variants, with a novel c.671_672del variant not previously described in literature. CONCLUSION: Based on the observations of this Turkish CTX cohort, it is emphasized that the true prevalence of CTX is probably underestimated and that it has a wide spectrum of clinical phenotypes even without neurological impairment. In children, abnormal cerebellar findings, peripheral neuropathy and psychiatric findings associated with intellectual disability have been suggested as warning signs to avoid diagnostic delay. In cases of clinical suspicion, molecular analysis is recommended despite normal plasma cholestanol levels, as severe neurologic involvement may occur in CTX patients without elevated cholestanol levels.

Experience with cascade screening: A comprehensive family pedigree analysis of two index patients with Fabry disease.

The wide range of clinical symptoms observed in patients with Fabry disease (FD) often leads to delays in diagnosis and initiation of treatment. Delayed initiation of therapy may result in end-organ damage, such as chronic renal failure, hypertrophic cardiomyopathy, and stroke. Although some tools are available to identify undiagnosed patients, new comprehensive screening methods are needed. In this study, the outcomes of the cascade screening applied to three index cases with FD from 2 familes were investigated. In the pedigree analysis, 280 individuals were included; out of them, 131 individuals underwent genetic testing and cascade screening for FD. During the screening program, a total of 45 individuals were diagnosed, with a diagnostic ratio of 1:15. The average age at diagnosis for all individuals was 30.9 ± 17.7 years, and %25 were pediatric cases (mean age 9.5 ± 5.9 years). Thirty affected relatives were diagnosed from the two index cases in Family 1 and 15 individuals were diagnosed from one index case in Family 2. There were 13 consanguineous marriages observed among 2 pedigres, in two both spouses  were affected, leading to two homozygous affected daughters in one couple. In regions where there is a high prevalence of consanguineous marriages, implementing the cascade screening approach to identify all individuals at risk can be beneficial for patients with FD, specifically women and children.

Could lysosomal acid lipase enzyme activity be used for clinical follow-up in cryptogenic cirrhosis?

BACKGROUND: Cholesterol ester storage disease (CESD) is one of the rare causes that should be kept in mind in the etiology of cirrhosis. Recent studies detected that significantly reduced lysosomal acid lipase deficiency enzyme (LAL) in patients with cryptogenic cirrhosis (CC). Moreover, studies have evaluated that LAL activity is as effective as scoring systems in assessing the severity of cirrhosis. In this study, we aimed to investigate the CESD with LAL level and mutation analysis of LIPA gene in patients diagnosed with CC and to compare LAL activities between patients with CC and healthy volunteers. METHODS: Laboratory parameters and cirrhosis stage (CHILD and MELD) were recorded for the patient group included in the study. In addition, blood samples were taken from each case included in the study for LAL activity determination and LIPA gene analysis. RESULTS: A statistically significant decrease in LAL activity was found in patients diagnosed with CC compared to the healthy group. LIPA gene analysis did not detect CESD in any patient group. Correlation analysis showed a positive correlation between LAL activity and white blood cell and platelet counts in both healthy volunteers and CC patient groups. In the univariate and multivariate logistic regression analysis of the parameters associated with the MELD of ≥10 in patients with CC, significant relationship was found between the MELD of ≥10 and the LAL activity. DISCUSSION: In our study, LAL activity was significantly lower in CC patients than in the normal population. LAL activity level appears to be a parameter that can be used to assess the severity of cirrhosis.

Familial Mediterranean Fever Mutation Analysis in Pediatric Patients With Inflammatory Bowel Disease: A Multicenter Study.

BACKGROUND: The aim of the study was to evaluate familial Mediterranean fever (FMF) mutation analysis in pediatric patients with inflammatory bowel disease (IBD). The relation between MEFV mutations and chronic inflammatory diseases has been reported previously. METHODS: Children with IBD (334 ulcerative colitis (UC), 224 Crohn's disease (CD), 39 indeterminate colitis (IC)) were tested for FMF mutations in this multicenter study. The distribution of mutations according to disease type, histopathological findings, and disease activity indexes was determined. RESULTS: A total of 597 children (mean age: 10.8 ± 4.6 years, M/F: 1.05) with IBD were included in the study. In this study, 41.9% of the patients had FMF mutations. E148Q was the most common mutation in UC and CD, and M694V in IC (30.5%, 34.5%, 47.1%, respectively). There was a significant difference in terms of endoscopic and histopathological findings according to mutation types (homozygous/ heterozygous) in patients with UC (P < .05). There was a statistically significant difference between colonoscopy findings in patients with or without mutations (P = .031, P = .045, respectively). The patients with UC who had mutations had lower Pediatric Ulcerative Colitis Activity Index (PUCAI) scores than the patients without mutations (P = .007). CONCLUSION: Although FMF mutations are unrelated to CD patients, but observed in UC patients with low PUCAI scores, it was established that mutations do not have a high impact on inflammatory response and clinical outcome of the disease.

Patients with cerebrotendinous xanthomatosis diagnosed with diverse multisystem involvement.

Cerebrotendinous xanthomatosis (CTX) is a lipid storage disease caused by deficiency of sterol 27-hydroxylase enzyme encoded by CYP27A1 gene. This multicenter, cross-sectional descriptive study aimed to document clinical characteristics of CTX patients of different ages, clinical presentations of early-diagnosed patients, and responses to short-term chenodeoxycholic acid (CDCA) treatment. Seven of 11 CTX patients were diagnosed in childhood. Three patients (27%) had neonatal cholestasis, seven (63%) patients had a history of frequent watery defecation started in infantile period, and eight (72.7%) patients had juvenile cataract. Four patients in the adult age group had pyramidal signs and parkinsonism symptoms. The mean Mignarri score at diagnosis was significantly lower in the pediatric patients (267.8 ± 51.4) than in the adult patients (450.0 ± 64.0, p = 0.001). No significant difference was determined between pediatric patients and adult patients regarding plasma cholestanol concentration at diagnosis (p = 0.482). The frequency of defecation decreased with treatment in six children, who had diarrhea at admission. Compared to pretreatment values, patients' body weight and standardized body mass index significantly increased at the 12th month of treatment. In conclusion, Mignarri scores are lower in the pediatric patients than in adult patients since the most determinative signs of the CTX disease are not apparent yet in the childhood. The disease is frequently overlooked in routine practice as the disease presents itself with different clinical combinations both in adults and in children. CTX is potentially a treatable disease; thereby, enhanced awareness is critically important for early diagnosis particularly in children.

Inflammatory rheumatic diseases in patients with ochronotic arthropathy.

BACKGROUND: Ochronotic arthropathy (OcA) refers to excessive homogentisic acid (HGA) deposition in the musculoskeletal system. Our current understanding of OcA is limited, as there are less than a thousand alkaptonuria (AKU) cases reported in the literature. Herein, we investigated the rheumatological manifestations of OcA in a group of adult AKU patients. METHODS: Adult AKU patients with symptoms suggestive of OcA were included. Patients underwent a detailed rheumatological assessment. Laboratory testing, including autoantibodies and radiological investigations such as conventional X-rays, and magnetic resonance imaging (MRI) were performed. RESULTS: Eight out of 12 (66%) patients had symptoms consistent with OcA. The median age at OcA symptoms was 36 (27-48) years, and the presenting symptom was back pain in 87.5% of the patients. All patients had chronic back pain, and three (37.5%) had an inflammatory type of pain character. Radiographic sacroiliitis based on X-rays was present in 2 (25%) cases. MRI of the sacroiliac joints documented bone marrow edema in five (62.5%), and spinal MRI identified corner inflammatory lesions in three patients (37.5%). One patient (12.5%) had rheumatoid arthritis. Extra-articular involvement, including enthesitis (n = 1; 12.5%), interstitial lung disease (n = 1; 12.5%), and scleritis (n = 1; 12.5%), was also noted. CONCLUSION: The frequent occurrence of OcA-related inflammatory manifestations in our patients contradicts the conventional concept of OcA as a non-inflammatory disorder. The activation of inflammatory pathways, possibly by the HGA products, may responsible for this condition.Significance and innovationsAbout three-fourths of adult ochronotic arthropathy (OcA) patients in our group had associated inflammatory disease.OcA associated inflammatory diseases were showing a severe phenotypeNearly half of the OcA patients required early prosthesis operations compared to their healthy counterparts.

ASAH1 pathogenic variants associated with acid ceramidase deficiency: Farber disease and spinal muscular atrophy with progressive myoclonic epilepsy.

Farber disease and spinal muscular atrophy with progressive myoclonic epilepsy are a spectrum of rare lysosomal storage disorders characterized by acid ceramidase deficiency (ACD), resulting from pathogenic variants in N-acylsphingosine amidohydrolase 1 (ASAH1). Other than simple listings provided in literature reviews, a curated, comprehensive list of ASAH1 mutations associated with ACD clinical phenotypes has not yet been published. This publication includes mutations in ASAH1 collected through the Observational and Cross-Sectional Cohort Study of the Natural History and Phenotypic Spectrum of Farber Disease (NHS), ClinicalTrials.gov identifier NCT03233841, in combination with an up-to-date curated list of published mutations. The NHS is the first to collect retrospective and prospective data on living and deceased patients with ACD presenting as Farber disease, who had or had not undergone hematopoietic stem cell transplantation. Forty-five patients representing the known clinical spectrum of Farber disease (living patients aged 1-28 years) were enrolled. The curation of known ASAH1 pathogenic variants using a single reference transcript includes 10 previously unpublished from the NHS and 63 that were previously reported. The publication of ASAH1 variants will be greatly beneficial to patients undergoing genetic testing in the future by providing a significantly expanded reference list of disease-causing variants.

[Fabry disease in cardiology: Diagnosis and therapeutic approaches]. / Kardiyolojide Fabry hastaligi: Tani ve tedavi yaklasimlari.

Fabry disease is a rare, progressive, X-linked inherited storage disorder due to absent or deficient of lysosomal alfa galactosidase A activity. Deficient activity of alfa-galactosidase A results in progressive accumulation of globotriaosylceramide in a variety of tissues and organs including myocardium, kidney and nerve system. This disorder predominantly affects males; however, female heterozygotes may also be affected with a less severe clinical picture. Classic Fabry disease is usually diagnosed in early age of childhood because of multiorgan involvement whereas cardiac and renal variants of Fabry are manifested in 30-50 years of age because of late onset of clinical picture in which other organs involvement are uncommon. Although Fabry is known as a very rare disease, its prevalence is reported to be higher in patients with ventricular hypertrophy, chronic kidney disease and cryptogenic stroke. From the cardiology point of view, the most important key finding of the disease is unexplained ventricular hypertrophy. However, in clinical practice, ventricular hypertrophy is usually thought to be due to hypertrophic cardiomyopathy in the absence of hypertension or aortic stenosis and Fabry disease is often undiagnosed or overlooked. Early diagnosis and enzyme replacement therapy have been shown to significantly improve prognosis. The aim of this paper is to provide a comprehensive review including epidemiology, prognosis, clinical presentation, diagnosis and therapeutic approaches of cardiac variant of Fabry based on the available data in the literature.

Robust, Long-Term Culture of Endoderm-Derived Hepatic Organoids for Disease Modeling.

Organoid technologies have become a powerful emerging tool to model liver diseases, for drug screening, and for personalized treatments. These applications are, however, limited in their capacity to generate functional hepatocytes in a reproducible and efficient manner. Here, we generated and characterized the hepatic organoid (eHEPO) culture system using human induced pluripotent stem cell (iPSC)-derived EpCAM-positive endodermal cells as an intermediate. eHEPOs can be produced within 2 weeks and expanded long term (>16 months) without any loss of differentiation capacity to mature hepatocytes. Starting from patient-specific iPSCs, we modeled citrullinemia type 1, a urea cycle disorder caused by mutations in the argininosuccinate synthetase (ASS1) enzyme. The disease-related ammonia accumulation phenotype in eHEPOs could be reversed by the overexpression of the wild-type ASS1 gene, which also indicated that this model is amenable to genetic manipulation. Thus, eHEPOs are excellent unlimited cell sources to generate functional hepatic organoids in a fast and efficient manner.

Efficacy and tolerability of olive oil-based ketogenic diet in children with drug-resistant epilepsy: A single center experience from Turkey.

PURPOSE: Ketogenic diet (KD) is an effective non-pharmacological treatment for drug-resistant epilepsy. The aim of this study was to investigate the efficacy, tolerability and complications of olive oil-based KD in epileptic children. METHOD: In this single-center, prospective study, patients were followed up at 1, 3, 6 and 12 months after KD initiation. Initially, blood ketone levels were measured daily, and as needed thereafter to maintain the levels between 4 and 5 mmol/L. Patient demographics, seizure frequency, serum biochemistry, abdominal ultrasonography and adverse effects were recorded. Efficacy of KD was defined as ≥50% seizure reduction. RESULTS: A total of 389 patients with drug-resistant epilepsy receiving KD from 2012 to 2016 were included. One hundred patients (25.7%) stopped the diet for different reasons in the first year, and 369, 314, 225 and 160 patients have been receiving KD treatment for 1, 3, 6 and 12 months, respectively. At 1, 3, 6 and 12th months, 65.8% (243/369), 74.7% (235/314), 70.6% (159/225) and 83.1% (133/160) of the patients were responders, respectively. None of the children had an increased seizure-frequency. Hyperlipidemia (50.8%), selenium deficiency (26.9%), constipation (26.2%), sleep disturbances (20.0%), nephrolithiasis (3.0%), hyperuricemia (3.0) and hepatic side effects (2.6%) were the most common complications of KD. Previous adrenocorticotropic hormone (ACTH) use due to epileptic encephalopathy and presence of constipation at baseline or during KD treatment were found the predictors of treatment efficacy. CONCLUSION: KD is an effective and well-tolerated treatment option for patients with drug-resistant epilepsy. Previous history of ACTH use and constipation during KD treatment are important factors that affect the efficacy of KD treatment.

Role of fecal calprotectin in the assessment of intestinal inflammation in children with familial Mediterranean fever.

AIM: Familial Mediterranean fever (FMF) is the most common auto-inflammatory disease with recurrent fever and serositis episodes. In recent years, some cases with FMF were reported with gastrointestinal involvement without amyloidosis, vasculitis and inflammatory bowel disease (IBD). It is not yet known whether gastrointestinal involvement is a part of the disease or not. The aim of this study is to investigate the frequency of intestinal inflammation by using a noninvasive method, fecal calprotectin measurement, in pediatric FMF patients. METHOD: Sixty-five FMF patients, 30 healthy controls and 11 patients with acute ulcerative colitis were included in the study. A standard survey inquiring gastrointestinal and other clinical symptoms was completed. The medications, MEFV mutations, whole blood count and C-reactive protein levels were recorded. Fecal calprotectin was studied with the enzyme-linked immunosorbent assay method from the feces samples of the all subjects. RESULTS: None of the FMF patients had clinical signs of IBD. Fecal calprotectin levels of the FMF patients were found to be significantly higher than the healthy controls (174.8 ± 150.8 vs 52.9 ± 36.5, p < 0.001). Fecal calprotectin levels of the ulcerative colitis patients were significantly higher than the FMF patients (523.5 ± 183 vs 174.8 ± 150.8, p = 0.001). There was a correlation between fecal calprotectin levels and neutrophil/lymphocyte ratio (r = 0.324, p = 0.009). CONCLUSION: Our results supported subclinical intestinal inflammation in pediatric FMF patients. Further studies are needed to clarify the reason for intestinal inflammation in FMF patients.

Elevated serum neopterin levels in children with functional constipation: association with systemic proinflammatory cytokines.

BACKGROUND: Functional constipation is a clinical problem with an incompletely understood etiology. Functional bowel diseases have been shown to be related to inflammation in many studies in adults. In this study, we aimed to evaluate leukocytes, C-reactive protein, proinflammatory and anti-inflammatory cytokines, and neopterin levels in children with functional constipation. METHODS: Seventy-six children with constipation and 71 healthy controls (mean age 7.12 ± 3.46 years and 7.32 ± 4.33 years, respectively, P = 0.991) were included in the study. Leukocytes, C-reactive protein, interleukin (IL)-1ß, IL-6, IL-10, IL-12, tumor necrosis factor-alpha (TNF-α) and neopterin levels were assessed in patients and healthy controls. Parameters were measured in the serum using enzyme-linked immunosorbent assay methods. RESULTS: Mean IL-6 (20.31 ± 12.05 vs. 16.2 ± 10.25 pg/mL, respectively, P = 0.003), IL-12 (181.42 ± 133.45 vs. 135.6 ± 83.67 pg/mL, respectively, P = 0.018) and neopterin levels (2.08 ± 1.12 vs. 1.52 ± 1.02 pg/mL, respectively, P = 0.001) were significantly higher in constipated children than healthy controls. Leukocyte and thrombocyte counts, C-reactive protein, and IL-1ß, IL-10 and TNF-α levels did not show any difference between the two groups. CONCLUSIONS: In this study, IL-6, IL-12 and neopterin levels of constipated patients were found to be higher than those of controls. These results indicate the presence of subclinical inflammation in children with functional constipation.

Acid Ceramidase Deficiency is characterized by a unique plasma cytokine and ceramide profile that is altered by therapy.

Acid Ceramidase Deficiency (Farber disease, FD) is an ultra-rare Lysosomal Storage Disorder that is poorly understood and often misdiagnosed as Juvenile Idiopathic Arthritis (JIA). Hallmarks of FD are accumulation of ceramides, widespread macrophage infiltration, splenomegaly, and lymphocytosis. The cytokines involved in this abnormal hematopoietic state are unknown. There are dozens of ceramide species and derivatives, but the specific ones that accumulate in FD have not been investigated. We used a multiplex assay to analyze cytokines and mass spectrometry to analyze ceramides in plasma from patients and mice with FD, controls, Farber patients treated by hematopoietic stem cell transplantation (HSCT), JIA patients, and patients with Gaucher disease. KC, MIP-1α, and MCP-1 were sequentially upregulated in plasma from FD mice. MCP-1, IL-10, IL-6, IL-12, and VEGF levels were elevated in plasma from Farber patients but not in control or JIA patients. C16-Ceramide (C16-Cer) and dhC16-Cer were upregulated in plasma from FD mice. a-OH-C18-Cer, dhC12-Cer, dhC24:1-Cer, and C22:1-Cer-1P accumulated in plasma from patients with FD. Most cytokines and only a-OH-C18-Cer returned to baseline levels in HSCT-treated Farber patients. Sphingosines were not altered. Chitotriosidase activity was also relatively low. A unique cytokine and ceramide profile was seen in the plasma of Farber patients that was not observed in plasma from HSCT-treated Farber patients, JIA patients, or Gaucher patients. The cytokine profile can potentially be used to prevent misdiagnosis of Farber as JIA and to monitor the response to treatment. Further understanding of why these signaling molecules and lipids are elevated can lead to better understanding of the etiology and pathophysiology of FD and inform development of future treatments.

Using Computerized Cytomorphometry to Distinguish between Benign and Malignant Cases in Thyroid Fine-Needle Aspiration Cytology.

BACKGROUND: Only a small number of studies on computerized cytomorphometry have been performed for thyroid FNAC. The present study aimed to determine the usefulness of computerized cytomorphometry methods to further classify thyroid lesions as benign or malignant and to compare the practicability and value of using Papanicolaou (Pap) and Giemsa stains in thyroid FNAC by evaluating their association to various cytologic nuclear parameters. METHODS: Fifty-eight thyroid lesions diagnosed by FNAC and categorized according to the Bethesda system for reporting thyroid cytopathology were evaluated in terms of various cytologic nuclear parameters, including nuclear area (NA), nuclear perimeter (NP), nuclear density (ND), long nuclear diameter (LND), and short nuclear diameter (SND). The Pap- and Giemsa-stained slides were examined separately. RESULTS: In the malignant cases, NA, NP, LND, and SND were higher than in the benign cases for both the Pap and Giemsa stains. NA, NP, LND, and SND were higher in Giemsa than Pap for both the benign and malignant groups. Statistically significant differences were detected between the benign and malignant cases in the AUS category. CONCLUSIONS: Computerized cytomorphometry is useful in distinguishing between benign and malignant lesions in thyroid FNAC. The measurement of cytologic nuclear parameters in cases suggestive of AUS may be useful for the probable classification of cases as benign or malignant. Although further studies are needed, in nuclear morphometric assessment of thyroid FNAC, Giemsa staining may be more useful and valuable than the Pap stain because of its association with various cytologic nuclear parameters. Diagn. Cytopathol. 2016;44:902-911. © 2016 Wiley Periodicals, Inc.

The effect of olive oil-based ketogenic diet on serum lipid levels in epileptic children.

Ketogenic diet (KD) is one of the most effective therapies for intractable epilepsy. Olive oil is rich in monounsaturated fatty acids and antioxidant molecules and has some beneficial effects on lipid profile, inflammation and oxidant status. The aim of this study was to evaluate the serum lipid levels of children who were receiving olive oil-based KD for intractable seizures at least 1 year. 121 patients (mean age 7.45 ± 4.21 years, 57 girls) were enrolled. At baseline and post-treatment 1, 3, 6, and 12 months body mass index-SDS, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride levels were measured. Repeated measure ANOVA with post hoc Bonferroni correction was used for data analysis. The mean duration of KD was 15.4 ± 4.1 months. Mean total cholesterol, LDL-cholesterol and triglyceride levels were significantly higher at 1st, 3rd, 6th and 12th months of the KD treatment, compared to pre-treatment levels (p = 0.001), but showed no difference among during-treatment measurements. Mean body mass index-SDS and HDL-cholesterol levels were not different among the baseline and follow-up time points (p = 0.113 and p = 0.067, respectively). No child in this study discontinued the KD because of dyslipidemia. Even if rich in olive oil, high-fat KD causes significant increase in LDL-cholesterol and triglyceride levels. More studies are needed to determine the effect of KD on serum lipids in children using different fat sources in the diet.

Fecal calprotectin: can be used to distinguish between bacterial and viral gastroenteritis in children?

OBJECTIVE: Fecal calprotectin is used as a good indicator of intestinal mucosal inflammation. The aim of this study is to evaluate the diagnostic value of fecal calprotectin (f-CP) for the etiology of acute gastroenteritis in children. MATERIALS AND METHODS: All patients presenting with acute diarrhea (<18 years) who had 3 or more soft or watery stools per day were enrolled in this study. Stool microscopic examination and cultures for bacteria and parasites were performed. Polymerase chain reaction test was also applied to stool samples for viruses (Rotavirus, Adenovirus, Norwalk, and Astrovirus). The level of f-CP was carried out by using enzyme-linked immunosorbent assay test. RESULTS: Eighty-four patients with diarrhea were enrolled. The f-CP level was higher in patients with microscopic examination positive (n=17) (median with interquartile range, 1610.0 [908.8-2100] mg/L) than in patients with microscopic examination negative (n=67) (123.8 [25.0-406.3] mg/L) (P<.001). Concentrations of f-CP in patients with stool culture positive (1870.0 [822.5-2100] mg/L) were significantly elevated compared with the concentrations of the patient with virus detected in stool (95.0 [21.3-240.9] mg/L) (P<.001). In the diagnosis for bacterial acute gastroenteritis, the area under the receiver operating characteristic curve for f-CP was 0.867 (95% confidence interval, 0.763-0.971), sensitivity was 88.9%, and specificity was 76.0% if the threshold was taken as 710 mg/L. CONCLUSION: We conclude that f-CP, which is useful, valuable, noninvasive, easily and rapidly measured laboratory test along with simple microscopic examination of stool, can be used as an indicator of intestinal inflammation and to distinguish the bacterial gastroenteritis from the viral gastroenteritis.

Obesity, fatty liver disease and intestinal microbiota.

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disorder that is increasing in prevalence with the worldwide epidemic of obesity. NAFLD is the hepatic manifestation of the metabolic syndrome. The term NAFLD describes a spectrum of liver pathology ranges from simple steatosis to steatosis with inflammation nonalcoholic steatohepatitis and even cirrhosis. Metabolic syndrome and NAFLD also predict hepatocellular carcinoma. Many genetic and environmental factors have been suggested to contribute to the development of obesity and NAFLD, but the exact mechanisms are not known. Intestinal ecosystem contains trillions of microorganisms including bacteria, Archaea, yeasts and viruses. Several studies support the relationship between the intestinal microbial changes and obesity and also its complications, including insulin resistance and NAFLD. Given that the gut and liver are connected by the portal venous system, it makes the liver more vulnerable to translocation of bacteria, bacterial products, endotoxins or secreted cytokines. Altered intestinal microbiota (dysbiosis) may stimulate hepatic fat deposition through several mechanisms: regulation of gut permeability, increasing low-grade inflammation, modulation of dietary choline metabolism, regulation of bile acid metabolism and producing endogenous ethanol. Regulation of intestinal microbial ecosystem by diet modifications or by using probiotics and prebiotics as a treatment for obesity and its complications might be the issue of further investigations.

Leptin-to-adiponectin ratio in obese adolescents with nonalcoholic fatty liver disease.

The leptin-to-adiponectin (L/A) ratio has been used to show insulin resistance (IR) in recent years. The aim of this study was to investigate the L/A ratio in obese adolescents and compare this ratio in patients with and without nonalcoholic fatty liver disease (NAFLD) and also with healthy controls. The second aim was to search the possible correlations between the L/A ratio with the markers of IR and inflammation. A total of 47 obese (mean age: 13.1±2.1 years) and 19 healthy children (mean age: 13.8±0.3 years) were included in the study. The presence of fatty liver was identified by ultrasonography. Cases were divided into three groups as NAFLD (+) and NAFLD (-) obese patients and controls. Liver biochemistries, insulin and serum lipids, C-reactive protein, tumor necrosis factor-alpha (TNF-alpha), interleukin-6, adiponectin, and leptin were determined. The L/A ratio was calculated. IR was estimated according to the homeostasis model assessment of insulin resistance (HOMA-IR). The L/A ratio was significantly higher in NAFLD (+) patients than in the other two groups, and in NAFLD (-) patients than the healthy peers. Moreover, L/A ratio correlated more strongly with weight for height (r: 0.528, p<0.0001), alanine aminotransferase (ALT) (r: 0.499, p<0.0001), triglyceride (r: 0.591, p<0.0001), and HOMA-IR (r: 0.574, p<0.0001) than did either leptin and adiponectin alone. This study shows that the L/A ratio is a noninvasive predictor of NAFLD in obese children and correlates with weight for height, ALT, triglyceride, and HOMA-IR better than each single adipokine.