Targeting resistant breast cancer stem cells in a three-dimensional culture model with oleuropein encapsulated in methacrylated alginate microparticles.

BACKGROUND: Cancer stem cells (CSCs) are a subpopulation of cancer cells that are believed to be responsible for tumor initiation, progression, metastasis, and resistance to conventional therapies. Oleuropein as a natural compound found in olive leaves and olive oil, has potential therapeutic effects in cancer treatment, particularly in targeting CSCs. It induces apoptosis in CSCs while sparing normal cells, inhibit proliferation, migration, and invasion, and suppress the self-renewal ability of CSCs. Additionally, oleuropein has shown synergistic effects with conventional chemotherapy drugs, enhancing their efficacy against CSCs. OBJECTIVES: This study aims to selectively target therapeutically resistant cancer stem cells (CSCs) within a heterogeneous tumor population by utilizing oleuropein (OLE) encapsulated in methacrylated alginate (OLE-mALG) within an in vivo-like microenvironment. PURPOSE: This study aims to target therapeutically resistant cancer stem cells (CSCs) with oleuropein (OLE) encapsulated in the methacrylated alginate (OLE-mALG) in a heterogeneous tumor population with an in vivo-like microenvironment. METHODS: Co-culture of CSCs with non-tumorogenic MCF-12 A cells was performed, the 3D breast cancer model was supported with methocel/matrigel/collagen-I, and vascularization was ensured with human umbilical vein endothelial cells (HUVEC). Then, OLE-loaded methacrylated alginate microparticles (mALG) were formed by dual crosslinking in the presence of both ionic and visible light obtained with a droplet based microfluidic system. The characterization and effectiveness of the produced OLE-mALG were evaluated by the FTIR, swelling/degradation/release analysis. Before producing OLE loaded mALG microparticles, a preliminary study was carried out to determine the effective dose of OLE for cells and the duration of OLE action on MCF-7, CSCs and MCF-12 A. Subsequently, CSC viability (WST-1), apoptosis (Bcl-2, Bax, caspase-3, caspase-9), stemness (OCT3/4, NANOG, SOX2), EMT profile (E-cadherin, Vimentin, Slug) and proliferation (SURVIVIN, p21, CYCLIN D1) after OLE-mALG treatment were all evaluated in the 3D model. RESULTS: OLE was encapsulated in mALG with an efficiency of 90.49% and released 73% within 7 h. OLE-mALG induced apoptosis through the decrease in anti-apoptotic Bcl-2 and an increase in pro-apoptotic Bax, caspase-3, and caspase-9 protein levels. While Vimentin and Slug protein levels decreased after 200 µg/mL OLE-mALG treatment to 3D breast cancer culture, E-cadherin levels increased. OLE-mALG treatment to CSC co-culture led to a decrease in proliferation by triggering p21/SURVIVIN expressions, and also resulted in an increase in stemness genes (OCT3/4/NANOG/SOX2). CONCLUSION: 200 µg/mL OLE-loaded mALG microparticles suppressed epithelial-to-mesenchymal transition by suppressing Vimentin and Slug protein levels, and increased E-cadherin levels in the 3D breast cancer model we created with CSCs, MCF-12 A and HUVECs. This complex system may allow the use of personalized cells for rapid drug screening in preclinical studies compared to animal experiments. OLE-mALG showed apoptotic and metastasis suppressive properties in cancer cells and it was concluded that it can be used in combination with or alternatively with chemotherapeutic agents to target breast cancer stem cells.

Evaluation of Tumorigenic Properties of MDA-MB-231 Cancer Stem Cells Cocultured with Telocytes and Telocyte-Derived Mitochondria Following miR-146a Inhibition.

Telocytes have some cytoplasmic extensions called telopodes, which are thought to play a role in mitochondrial transfer in intercellular communication. Besides, it is hypothesized that telocytes establish cell membrane-mediated connections with breast cancer cells in coculture and may contribute to the survival of neoplastic cell clusters together with other stromal cells. The aim of this study is to investigate the contribution of telocytes and telocyte-derived mitochondria, which have also been identified in breast tumors, to the tumor development of breast cancer stem cells (CSCs) via miR-146a-5p. The isolation/characterization of telocytes from bone marrow mononuclear cells and the isolation of mitochondria from these cells were performed, respectively. In the next step, CSCs were isolated from the MDA-MB-231 cell line and were characterized. Then, miR-146a-5p expressions of CSCs were inhibited by anti-miR-146a-5p. The epithelial-mesenchymal transition (EMT) was determined by evaluating changes in vimentin protein levels and was evaluated by analyzing BRCA1, P53, SOX2, E-cadherin, and N-cadherin gene expression changes. Our results showed that miR-146a promoted stemness and oncogenic properties in CSCs. EMT (N-cadherin, vimentin, E-cadherin) and tumorigenic markers (BRCA1, P53, SOX2) of CSCs decreased after miR-146a inhibition. Bone marrow-derived telocytes and mitochondria derived from telocytes favored the reduction of CSC aggressiveness following this inhibition.

The role of telocytes and miR-21-5p in tumorigenicity and metastasis of breast cancer stem cells.

BACKGROUND: This study aims to investigate the roles of telocytes on the metastatic properties of breast cancer stem cells (CSCs), and to re-evaluate the effect of miR-21-5p expression on CSCs following the addition of telocytes. METHODS AND RESULTS: Telocytes from human bone marrow mononuclear cells were isolated/characterised. This was followed by the isolation/characterisation of CSCs from the MDA-MB-231. miR-21-5p was both overexpressed/inhibited in CSCs. Through co-culture studies, EMT transition and oncogenic properties of CSCs were investigated by analysing changes in ALDH1 and vimentin protein levels as well as changes in the ABCC11, SNAI1, LZTFL1, Oct 3/4, E- and N-cadherin gene expression levels. With the inhibition of miR-21-5p, significant increases in LZTFL and ABCC11 were observed with the addition of telocytes. The expression of the LZTFL gene, which decreased with the overexpression of miR-21-5p, increased in CSCs after co-culture with telocytes. While an increase expression of ABCC11, SNAI1, N-Cadherin, vimentin and ALDH was observed in CSCs after overexpression of miR-21-5p, significant decreases in these expressions were observed after co-culture with telocyte. CONCLUSIONS: In our study, by gene/protein level analysis we demonstrated that telocytes may have the potential to reduce cancer metastasis through miR-21-5p in breast cancer progression and reduce EMT transition.

In Vitro Cytotoxicity and Oxidative Stress Evaluation of Valerian (Valeriana officinalis) Methanolic Extract in Hepg2 and Caco2 Cells

Objectives: Traditional treatment methods are becoming popular and commonly used in many societies and have become the first treatment option for most people. While some of these methods are helpful, they can interact with medications the patient is taking for another disease and cause a variety of life-threatening risks. Valerian (catweed) plant is used in traditional medicine as a sleep aid due to its sedative effects. Valerian may also exert anticancer effect in vitro. Materials and Methods: In this study, the cytotoxicty and oxidative stress effects of valerian root extract were evaluated in human liver hepatocellular carcinoma (Hepg2) and human colorectal adenocarcinoma (Caco2) cell lines. The cytotoxicity was evaluated via the 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide test. Total reactive oxygen species analysis was performed via a 2',7'-dichlorodihydrofluorescein diacetate assay in flow cytometry. Results: Inhibition concentration 50 values were calculated as 936.6 and 1097.5 µg/mL in the Hepg2 and Caco2 cell lines, respectively. It was observed that valerian root extract did not induce oxidative stress in HepG2 and Caco2 cell lines. Conclusion: These results indicate that the use of valerian root extract as an alternative method in cancer treatment may not be effective and may cause a risk for public health. On the other hand, it may be safe at recommended tolerated concentrations since it does not cause oxidative stress.

Neuroprotective and memory-enhancing effects of methanolic leaf extract of Peristrophe bicalyculata in rat model of type 2 diabetes mellitus.

This study investigated the effect of methanolic leaf extract of Peristrophe Bicalyculata (MEPb) on type 2 diabetes mellitus (T2DM) associated cognitive decline in Wistar rats. 36 male rats weighing 130-200 g were assigned into 6 groups (n = 6) as follows: normal control, diabetic control, pioglitazone-treated diabetic and three MEPb-treated diabetic groups, type 2 diabetes mellitus was induced with low dose streptozocin (STZ) injection following 3 weeks of high fat diet (HFD) intake. Thirty days after diabetes induction, rats exhibited marked and persistent hyperglycemia, animals were treated with MEPb (50, 100 and 200 mg/kg) and pioglitazone (10 mg/kg) as standard. Morris water maze (MWM) test and Novel object recognition test (NORT) were used to assess learning and memory. Blood glucose level, oxidative stress makers, pro-inflammatory marker and acetylcholinestarase activities were analysed. Both MEPb and pioglitazone significantly (P < 0.05) reduced escape latency in treated animals compared to the diabetic control group in the MWM test. Methanolic leaf extract of Peristrophe bicalyculata and pioglitazone also significantly (P < 0.05) increased discrimination index in treated animals compared to the diabetic control group in the novel object recognition test. Serum, brain and liver MDA levels were significantly (P < 0.05) decreased in MEPb and pioglitazone treated rats compared to diabetic control. Serum and liver GSH as well as CAT levels were significantly (P < 0.05) increased while brain GSH and CAT levels shows apparent increase in MEPb and pioglitazone treated rats compared with diabetic control. Treatment with MEPb caused a significant (P < 0.05) decrease in brain nitrite level, interleukin 6 and acetylcholinesterase activity compared to diabetic control group. We conclude that Methanolic leaf extract of Peristrophe bicalyculata enhanced antioxidant capacity and prevented neuroinflammation, consequently improving brain neuronal cholinergic function in experimental animals.

Subchronic exposure to Kafura; its neurotoxic potentials in young adult female Wistar rats.

BACKGROUND: Kafura pelebe (camphor) {C10H16O} is a chemical substance used mostly amongst the Yoruba ethnic group in Western Nigeria to treat infantile colic during early childhood. This study assess the neurotoxic potentials of Kafura following sub-chronic exposure in female albino Wistar rats. METHODS: Twenty-eight female rats (mean weight of 130 g) were randomly selected and assigned into four (4) groups. Control, received 1ml coconut oil while the treatment groups received 79, 158 and 237. mg/kg b.wt (d ose p.o) of Kafura for the period of 14 days. On day fifteen, animals were dissected and the brain organ excised for the homogenate and histopathologic assay, blood samples were also collected for haematological analysis. Morris Water Maze experiment for reference memory was also carried out to ascertain effect of Kafura in the Central Nervous system (CNS). RESULTS: A trend toward decreased body-weight gain and increase brain weight was observed in Kafura-treated rats but was statistically not significant, compared to control. The biochemical assessment of the antioxidant status of brains of Kafura-treated rats showed significant (p ≤ 0.05) increase in activities of some anti-oxidant enzymes (Superoxide dismutase (SOD), Glutathione peroxide (GPx), and Catalase (CAT)). There was increase in acetylcholinesterase (AChE), Malondialdehyde (MDA), and Total protein activities in the brain of treated rats compared to control. Alterations of the haematological parameters were observed, with the plasma granulocytes, lymphocytes, and haemoglobin (HGB), showing significant decrease in the treated rats compared to control. The water maze test showed a marked increase in spatial learning and memory time (seconds) in kafura-treated rats, compared to control and across treated groups. CONCLUSIONS: The present study provides indication that kafura Pelebe shows apparent neurotoxicity in experimental animals. Incessant exposure in humans though may lead to development of some central nervous system defects.

Long-Term Outcome of Steroid-Resistant Nephrotic Syndrome in Children.

We investigated the value of genetic, histopathologic, and early treatment response information in prognosing long-term renal outcome in children with primary steroid-resistant nephrotic syndrome. From the PodoNet Registry, we obtained longitudinal clinical information for 1354 patients (disease onset at >3 months and <20 years of age): 612 had documented responsiveness to intensified immunosuppression (IIS), 1155 had kidney biopsy results, and 212 had an established genetic diagnosis. We assessed risk factors for ESRD using multivariate Cox regression models. Complete and partial remission of proteinuria within 12 months of disease onset occurred in 24.5% and 16.5% of children, respectively, with the highest remission rates achieved with calcineurin inhibitor-based protocols. Ten-year ESRD-free survival rates were 43%, 94%, and 72% in children with IIS resistance, complete remission, and partial remission, respectively; 27% in children with a genetic diagnosis; and 79% and 52% in children with histopathologic findings of minimal change glomerulopathy and FSGS, respectively. Five-year ESRD-free survival rate was 21% for diffuse mesangial sclerosis. IIS responsiveness, presence of a genetic diagnosis, and FSGS or diffuse mesangial sclerosis on initial biopsy as well as age, serum albumin concentration, and CKD stage at onset affected ESRD risk. Our findings suggest that responsiveness to initial IIS and detection of a hereditary podocytopathy are prognostic indicators of favorable and poor long-term outcome, respectively, in children with steroid-resistant nephrotic syndrome. Children with multidrug-resistant sporadic disease show better renal survival than those with genetic disease. Furthermore, histopathologic findings may retain prognostic relevance when a genetic diagnosis is established.

Idiopathic central diabetes insipidus presenting in a very low birth weight infant successfully managed with lyophilized sublingual desmopressin.

Neonatal central diabetes insipidus (DI) is an extremely rare disorder that can cause severe morbidity and mortality. We have reported a very low birth weight infant with idiopathic central DI presenting in the first month of life who was successfully treated with sublingual desmopressin therapy. In this report, we emphasize that central DI should be kept in mind in an infant with unexplained hypernatremia and polyuria. Timely diagnosis and treatment with lyophilized desmopressin may prevent severe morbidity and mortality.

Assessment of left ventricular functions with tissue Doppler, strain, and strain rate echocardiography in patients with familial Mediterranean fever.

OBJECTIVE: This study assessed the early changes in regional and global systolic and diastolic myocardial functions in patients with familial Mediterranean fever without any cardiovascular symptoms using tissue Doppler and strain and strain rate echocardiography and compared them to the results of a control group. METHODS: This study has a cross-sectional and observational design. FMF patients with normal left ventricular function were included in the study. We excluded patients who had arrhythmia, acquired/congenital heart disease, pericarditis, or acute attack. We compared 45 children with familial Mediterranean fever on colchicine therapy and 45 age- and sex-matched healthy children. RESULTS: The 45 patients with familial Mediterranean fever included 24 (55.3%) girls and 21 (46.7%) boys with a mean age of 11.3 ± 3.7 (range 2-18) years. The mean disease duration was 4.6 ± 2.4 (range 0.5-10) years. In the patient group, the homozygous M694V mutation was the most common (64.4%) mutation. The patients with familial Mediterranean fever had statistically lower longitudinal global strain, radial global strain, and strain rates (-14.44 ± 4.77%, 14.80 ± 6.29%, and 0.59 ± 0.24 s, respectively) than the controls (-17.40 ± 1.79%, 17.53 ± 4.63%, and 0.83 ± 0.51 s) (p < 0.05). The circumferential global strain did not differ significantly between the groups. CONCLUSION: Patients with familial Mediterranean fever who are subclinical from a cardiac aspect might have normal left ventricular function as measured by conventional echocardiography. However, the disease affects their myocardial tissue, and these patients should be followed with conventional, strain, and strain rate echocardiography techniques regularly.

Spectrum of steroid-resistant and congenital nephrotic syndrome in children: the PodoNet registry cohort.

BACKGROUND AND OBJECTIVES: Steroid-resistant nephrotic syndrome is a rare kidney disease involving either immune-mediated or genetic alterations of podocyte structure and function. The rare nature, heterogeneity, and slow evolution of the disorder are major obstacles to systematic genotype-phenotype, intervention, and outcome studies, hampering the development of evidence-based diagnostic and therapeutic concepts. To overcome these limitations, the PodoNet Consortium has created an international registry for congenital nephrotic syndrome and childhood-onset steroid-resistant nephrotic syndrome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Since August of 2009, clinical, biochemical, genetic, and histopathologic information was collected both retrospectively and prospectively from 1655 patients with childhood-onset steroid-resistant nephrotic syndrome, congenital nephrotic syndrome, or persistent subnephrotic proteinuria of likely genetic origin at 67 centers in 21 countries through an online portal. RESULTS: Steroid-resistant nephrotic syndrome manifested in the first 5 years of life in 64% of the patients. Congenital nephrotic syndrome accounted for 6% of all patients. Extrarenal abnormalities were reported in 17% of patients. The most common histopathologic diagnoses were FSGS (56%), minimal change nephropathy (21%), and mesangioproliferative GN (12%). Mutation screening was performed in 1174 patients, and a genetic disease cause was identified in 23.6% of the screened patients. Among 14 genes with reported mutations, abnormalities in NPHS2 (n=138), WT1 (n=48), and NPHS1 (n=41) were most commonly identified. The proportion of patients with a genetic disease cause decreased with increasing manifestation age: from 66% in congenital nephrotic syndrome to 15%-16% in schoolchildren and adolescents. Among various intensified immunosuppressive therapy protocols, calcineurin inhibitors and rituximab yielded consistently high response rates, with 40%-45% of patients achieving complete remission. Confirmation of a genetic diagnosis but not the histopathologic disease type was strongly predictive of intensified immunosuppressive therapy responsiveness. Post-transplant disease recurrence was noted in 25.8% of patients without compared with 4.5% (n=4) of patients with a genetic diagnosis. CONCLUSIONS: The PodoNet cohort may serve as a source of reference for future clinical and genetic research in this rare but significant kidney disease.

Diagnostic validity of colchicine in patients with Familial Mediterranean fever.

Although response to colchicine has been proposed as one of the diagnostic criteria in patients with Familial Mediterranean fever (FMF), the validity of this response has not been validated. The aim of this study was to assess the efficacy of the response to colchicine and to evaluate the extent of the effect of placebo. A double-blind randomized placebo-controlled trial with a cross-over design was conducted. The frequency of FMF attacks, the disease score, physical examination, and acute phase reactants were assessed at 0, 3, and 6 months. Blood samples were collected for complete blood count (CBC), erythrocyte sedimentation rate (ESR), levels of serum C-reactive protein (CRP) and serum amyloid A (SAA), and MEFV mutation analysis in 79 patients with a preliminary diagnosis of FMF. Patients were randomly allocated to receive either drug A or drug B in a double-blind fashion. The designated drug was switched at 3 months. Patients taking colchicine had less frequent FMF attacks (median 0) and lower FMF disease score (median 0) when compared to those on placebo (median 1 and 3, respectively) (p = 0.002 and p = 0.007, respectively). In genetically confirmed FMF patients, median attack number and median disease score was 0 under colchicine treatment, whereas these parameters were significantly higher in the placebo group (median 2 and 8, respectively) (p = 0.007 and p = 0.02, respectively) suggesting that colchicine is more effective than placebo in reducing attacks and disease score. Positive and negative predictive values were 70.2 and 37.5 %, respectively. During the placebo period, patients had less FMF attacks when compared to that of the pre-study period (median 2 vs 6, respectively) (p < 0.001). The high false positive rate raises concerns for considering the colchicine response test as diagnostic for FMF. The role of placebo on the attacks of periodic fever syndromes needs to be further investigated.

FMF50: a score for assessing outcome in familial Mediterranean fever.

BACKGROUND: Colchicine is the main treatment for familial Mediterranean fever (FMF). However, biological agents and other treatments are available for patients who are unable to receive optimal treatment. OBJECTIVE: To develop outcome criteria that define response to treatment. METHODS: Two rounds of Delphi exercise were followed by a consensus conference enabling the definition of the criteria to be employed. Data for patients with FMF responding and resistant to their treatment were obtained from the FMF Arthritis Vasculitis and Orphan disease Research in paediatric rheumatology (FAVOR) website. The suggested criteria were analysed and validated in this patient cohort. Sensitivity/specificity measures and the ability of the score to discriminate between patients with active and inactive disease via the best cut-off score were calculated by a receiver operating characteristic analysis. RESULTS: Compliance with the maximum dose of the drug was considered essential for evaluation of the patients. Seven criteria were suggested in the consensus conference. The performance of each criterion, in differentiating between resistant and responsive patients, was tested. The final set of criteria was defined as at least 50% improvement in five of six criteria, without worsening in any one defined response to treatment with a very high sensitivity and specificity. The items of this FMF50 included: 1. Percentage change in the frequency of attacks with the treatment. 2. Percentage change in the duration of attacks with the treatment. 3. Patients/parents' global assessment of disease severity (10 cm visual analogue scale (VAS)). 4. Physicians' global assessment of disease severity (10 cm VAS). 5. Percentage change in arthritis attacks with the treatment. 6. Percentage change in C-reactive protein, erythrocyte sedimentation rate or serum amyloid A level with the treatment. CONCLUSIONS: The FMF50 produced is a user-friendly measurement tool to guide physicians and can be used in clinical trials.

Genotype-phenotype associations in WT1 glomerulopathy.

WT1 mutations cause a wide spectrum of renal and extrarenal manifestations. Here we evaluated disease prevalence, phenotype spectrum, and genotype-phenotype correlations of 61 patients with WT1-related steroid-resistant nephrotic syndrome relative to 700 WT1-negative patients, all with steroid-resistant nephrotic syndrome. WT1 patients more frequently presented with chronic kidney disease and hypertension at diagnosis and exhibited more rapid disease progression. Focal segmental glomerulosclerosis was equally prevalent in both cohorts, but diffuse mesangial sclerosis was largely specific for WT1 disease and was present in 34% of cases. Sex reversal and/or urogenital abnormalities (52%), Wilms tumor (38%), and gonadoblastoma (5%) were almost exclusive to WT1 disease. Missense substitutions affecting DNA-binding residues were associated with diffuse mesangial sclerosis (74%), early steroid-resistant nephrotic syndrome onset, and rapid progression to ESRD. Truncating mutations conferred the highest Wilms tumor risk (78%) but typically late-onset steroid-resistant nephrotic syndrome. Intronic (KTS) mutations were most likely to present as isolated steroid-resistant nephrotic syndrome (37%) with a median onset at an age of 4.5 years, focal segmental glomerulosclerosis on biopsy, and slow progression (median ESRD age 13.6 years). Thus, there is a wide range of expressivity, solid genotype-phenotype associations, and a high risk and significance of extrarenal complications in WT1-associated nephropathy. We suggest that all children with steroid-resistant nephrotic syndrome undergo WT1 gene screening.

Genetic screening in adolescents with steroid-resistant nephrotic syndrome.

Genetic screening paradigms for congenital and infantile nephrotic syndrome are well established; however, screening in adolescents has received only minor attention. To help rectify this, we analyzed an unselected adolescent cohort of the international PodoNet registry to develop a rational screening approach based on 227 patients with nonsyndromic steroid-resistant nephrotic syndrome aged 10-20 years. Of these, 21% had a positive family history. Autosomal dominant cases were screened for WT1, TRPC6, ACTN4, and INF2 mutations. All other patients had the NPHS2 gene screened, and WT1 was tested in sporadic cases. In addition, 40 sporadic cases had the entire coding region of INF2 tested. Of the autosomal recessive and the sporadic cases, 13 and 6%, respectively, were found to have podocin-associated nephrotic syndrome, and 56% of them were compound heterozygous for the nonneutral p.R229Q polymorphism. Four percent of the sporadic and 10% of the autosomal dominant cases had a mutation in WT1. Pathogenic INF2 mutations were found in 20% of the dominant but none of the sporadic cases. In a large cohort of adolescents including both familial and sporadic disease, NPHS2 mutations explained about 7% and WT1 4% of cases, whereas INF2 proved relevant only in autosomal dominant familial disease. Thus, screening of the entire coding sequence of NPHS2 and exons 8-9 of WT1 appears to be the most rational and cost-effective screening approach in sporadic juvenile steroid-resistant nephrotic syndrome.

The association between urinary tract infection and idiopathic hypercalciuria in children.

BACKGROUND: Identifying the risk factors is important in prevention of urinary tract infections (UTIs) in children. The aim of this study is to evaluate the association of UTI and idiopathic hypercalciuria (IHC). METHODS: Two hundred and twenty-four children aged between 1 month and 16 years and diagnosed to have UTI were evaluated for urinary calcium excretion. The children were diagnosed to have IHC if their urinary calcium/creatinine ratios in at least two different spot urine samples were >0.6 between 0-1 year old and ≥0.21 over 1 year or daily calcium excretion >4 mg/kg. RESULTS: The frequency of IHC was found to be 16.7%. Family history of urolithiasis, parental consanguinity, presentation with abdominal pain, loss of appetite, and discomfort were found to be significantly higher in the IHC group. No association was found between IHC and the recurrence of UTI, presence of vesicoureteral reflux, renal scar formation, and the prognosis. CONCLUSIONS: IHC should be considered among the risk factors for UTI and should be investigated particularly in patients with family history of urinary stones and suggestive complaints of IHC.

Can sonographic peritoneal thickness be used to follow pediatric patients on peritoneal dialysis?

BACKGROUND: Peritoneal dialysis (PD) is an effective and successful therapy for end-stage renal disease (ESRD). However, PD does not have a life-long effectiveness, and peritoneal membrane failure is commonly observed in long-term PD patients. We hypothesized that ultrasonography could be used to follow these patients. METHODS: We recruited two patient groups (age range 3-18 years), of whom 20 had ESRD with ongoing PD for ≥24 months (study group) and 20 were pre-dialysis non-ESRD patients (control group). None of the patients had peritonitis during the preceding 3 months, and none had a history of abdominal surgery or malignancy. We measured the sonographic thickness of the parietal peritoneum and obtained Doppler indices of the superior mesenteric artery (SMA) by trans-abdominal ultrasonography. RESULTS: Peritoneal thickness as determined by sonography was significantly greater in the PD group than in the controls. The correlation between duration of PD and thickness of the peritoneal membrane was linear and statistically significant. We categorized all 20 patients as either rapid transporters or slow transporters for both creatinine and glucose. The peritoneal membranes of patients who were rapid transporters for both creatinine and glucose were significantly thicker than those of the slow transporters. No statistical difference was found between the Doppler indices of the SMA between the groups. CONCLUSION: Thickness of the parietal peritoneum as determined by sonography is associated with PD duration and transport characteristics. We conclude that ultrasonography is a non-invasive and practical method which can be useful for following PD patients.

An unusual case of ANA negative systemic lupus erythematosus presented with vasculitis, long-standing serositis and full-house nephropathy.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that may affect any organ of the body. We report here an unusual case of seronegative SLE presented as vasculitis with rash, lower gastrointestinal system bleeding and acute renal failure. The patient was a 13-year-old boy, with abdominal distention, pretibial edema, arthritis and petechia on bilateral ankles. He had deteriorated renal functions (creatinine 1.65 mg/dl), hypoalbuminemia (1.6 g/dl) and hypocomplementemia with nephrotic range proteinuria and hematuria. He developed pleural effusion and peritonitis. Serum ANA, anti dsDNA, p ANCA, c ANCA, anticardiolipin IgM and IgG titers were negative. A renal biopsy was performed which revealed diffuse proliferative glomerulonephritis with full-house staining pattern in immunofluorescent microscopic examination suggesting Class IV Lupus Nephritis. He was administered a total of six courses of monthly intravenous pulse methyl prednisolone, dipyridamole, oral cyclophosphamide followed by azothiopirine and oral prednisolone therapy. The renal functions and serum albumin levels turned normal but peritonitis persisted and disappeared after the third pulse steroid therapy. In conclusion, we presented this patient to remind the possibility of SLE in such seronegative patients with unusual findings in order to avoid the delay in the management of this disease with high mortality and morbidity if not treated. Full-house nephropathy is an important clue especially for the diagnosis of ANA negative SLE.

The comparition of the efficacy of two different probiotics in rotavirus gastroenteritis in children.

Objectives. The aim of the study is to compare the clinical effectiveness of the probiotics-Saccharomyces boulardii and Bifidobacterium lactis-in children who had been diagnosed with rotavirus gastroenteritis. Materials and methods. Seventy five patients aged between 5 months-5 years diagnosed as rotavirus gastroenteritis were included in the study. The patients diagnosed as rotavirus gastroenteritis by latex agglutination test in stool were divided into 3 groups of twenty-five patients each: First group was given oral rehydration therapy and rapid refeeding with a normal diet with Saccharomyces boulardii (spp. I-745), second group was given oral rehydration therapy and rapid refeeding with a normal diet with Bifidobacterium lactis (spp. B94, culture number:N°118529) and third group received only oral rehydration therapy and rapid refeeding with a normal diet. Results. The duration of diarrhea was shorter in the group given oral rehydration therapy and rapid refeeding with a normal diet with Bifidobacterium lactis and Saccharomyces boulardii than the group given only oral rehydration therapy and rapid refeeding with a normal diet. Conclusion. Bifidobacterium lactis has a complemental role in the treatment of rotavirus gatroenteritis and other probiotics may also have a beneficial effect in rotavirus gastroenteritis compared with the therapy included only oral rehydration therapy and rapid refeeding with a normal diet.

[Assessment of left ventricular functions with tissue Doppler, strain and strain rate echocardiography in children with juvenile idiopathic arthritis: An observational study]. / Juvenil idiyopatik artritli çocuklarda sol ventrikül fonksiyonlarinin doku Doppler, gerilme ve gerilme hizi ekokardiyografi ile degerlendirilmesi: Gözlemsel bir çalisma.

OBJECTIVE: In juvenile idiopathic arthritis (JIA) cardiac involvement is usually silent without typical symptoms. The purpose of this study was to assess left ventricular functions with tissue Doppler echocardiography (TDE), strain and strain rate in children with JIA. METHODS: Our study was designed as a cross-sectional observational study. Thirty pediatric patients with JIA and 30 age- and sex-matched healthy controls were studied. In addition to standard echocardiographic methods, tissue Doppler, strain and strain rate imaging's were performed to assess left ventricular functions in all participants. The means of variables that did not distributed normally were compared with Mann-Whitney U test. RESULTS: In patients with JIA, E' values of mid and apical regions of left ventricular lateral wall were significantly lower than those of the controls (15.76±3.24 vs 17.91±3.29 cm/s, 11.10±2.96 vs12.64± 2.42 cm/s, p<0.05). In longitudinal strain reflecting left ventricular regional systolic functions, apical-lateral, basal and mid-septum peak S values, lateral peak S values in circumferential strain (-17.30±6.22 vs -21.97±4.32, -18.23±4.62 vs -21.53±2.69, -20.35±3.75 vs -22.75±3.50, -9.68±7.12 vs -13.70±6.81 cm/s, p<0.05, r:0.42, 0.41, 0.42), in longitudinal strain reflecting diastolic functions, apical-lateral, mid-lateral, apical-septum, mid-septum peak E values (2.22±1.00 vs 3.17±0.87, 1.62±0.84 vs 2.15±0.72, 2.51±0.76 vs 3.31±0.87, 1.99±0.64 vs 2.47±0.57 cm/s, p<0.05, r:-0.39,-0.55,-0.43) and in circumferential strain lateral and posterior peak E values (1.32±0.83 vs 1.88±0.94, 1.31±0.71 vs 1.85±0.91 cm/s, p<0.05, r:-0.33, -0.22) were significantly lower than those of the controls. CONCLUSION: Although marked myocardial involvement was not detected with tissue Doppler imaging in JIA patients with subclinical cardiac disease, regional impairments in left ventricular strain and strain rates were found.

Hyperprolactinemia as a rare cause of hypertension in chronic renal failure.

Chronic renal failure (CRF) is associated with a high risk for hypertension. An individualized treatment should be initiated after the diagnosis of hypertension and underlying etiology. Many metabolic and endocrinal abnormalities are encountered in CRF. We present an 11-year-old boy with CRF developing galactorrhea and hyperprolactinemia associated with α-methyldopa, defective dopaminergic control, and resistance to multi-antihypertensive therapy. Cabergoline, a dopamine receptor agonist, was effectively used in the treatment of hypertension. It is important to remember that sometimes treatment of an illness becomes the cause of this illness.