Search

Background: Despite being a long-term therapy for patients with short bowel syndrome (SBS), subcutaneous injections of teduglutide promote the regeneration of the gastrointestinal tract. Such cases are particularly concerning for patients with residual small bowel. Methods: In this report, we present a case of an SBS patient with only 5 cm of remaining small bowel and a high-output duodenal stoma, who was treated with teduglutide. Results: The initiation of teduglutide injections in our patient resulted in a reduction of stoma output, improvement in the patient’s nutritional status, regulation of fluid balance, and stabilization of their clinical condition. Conclusions: This case suggests that subcutaneous injections of teduglutide, when combined with appropriate nutritional care, can effectively treat high-output stomas, even in cases where the small bowel is nearly absent.

The cardiovascular performance of salmonids in aquaculture can be impaired by acute climate warming, posing risks for fish survival. Exercise training and functional feeds have been shown to be cardioprotective in mammals but their action on the fish heart and its upper thermal performance has not been studied. To investigate this, rainbow trout were trained at a moderate water velocity of 1 body length per second (bl s−1) for 6 h per day, either alone or in combination with one of two functional feed-supplements, allicin and fucoidan. After 6 weeks of exercise training and feeding, maximum heart rate and the temperature coefficient of heart rate were significantly higher in the trained fish as compared to untrained ones. There was a slight increase in hematocrit in trained control fish reared on a normal diet (TC group) compared to untrained fish fed with the same diet (CC). This implies that exercise training enhanced oxygen delivery to trout tissues via an increase of cardiac blood flow in warm water. However, cardiac thermal tolerance was not affected by exercise training or feeding, except from the temperature of peak heart rate which was higher in the trained group fed with fucoidan supplement (TF) as compared to the untrained group fed with same diet (CF). Allicin supplement caused a significant reduction in the maximum heart rate and the temperature coefficient of heart rate, especially in trained fish, while fucoidan supplement did not cause any effect on heart rate. No differences were observed in growth performance among groups. However, fish fed with fucoidan-supplemented diet had a slight reduction in feed conversion efficiency. We suggest further investigations to understand the antagonistic effect of allicin supplemental feeding and exercise training on cardiovascular performance. More studies are also required to investigate if other exercise training intensities could increase cardiac thermal tolerance.

Purpose: Studies examining association of estrogen receptor alpha (ERα) polymorphisms with early puberty are scarce and results are controversial; data in Caucasian girls are lacking. Main objective was to determine association of Xbal and Pvull polymorphisms of ERα gene in Greek girls with precocious/early puberty Methods: We studied 107 girls with idiopathic precocious/early puberty and 81 young women with pubertal maturation within normal age (controls). Pubertal stage, height SDS (HSDS), and BMI z-score were determined in patients. In controls, height was measured and menarcheal age was self-reported. All participants in the study were genotyped for XbaI and PvuII polymorphisms of the ERα gene. Results: There was no significant difference in XbaI and PvuII polymorphisms between patients and controls. Homozygous, xx and pp, girls had an earlier onset of puberty, although non-significant, than heterozygous or with no polymorphisms p= 0.9; in girls with pubertal onset <7 years, the association tended to become significant, p= 0.09. Girls with xxpp genotype were significantly taller, HSDS 1.63, p= 0.014. In controls, homozygosity for Xbal (xx) and PvuII (pp) was associated with significantly earlier menarche than in women with no polymorphism, p= 0.013 and p= 0.026, respectively, and xxpp genotype was associated with taller adult height, p= 0.017. Conclusion: XbaI and PvuII polymorphisms are not related to idiopathic precocious/early puberty. Early pubertal girls homozygous for both polymorphisms presented earlier onset of puberty, although statistically non-significant, and taller height than girls heterozygous or without these polymorphisms. Homozygosity for both polymorphisms is associated with earlier menarche and taller adult height.

Flavobacterium psychrophilumproduces biofilms under laboratory conditions, and it has been inconclusively suggested that F. psychrophilumbiofilms can be a potential reservoir for transmission of the pathogen to a fish population under fish farming conditions. Therefore, there is a need for anti‐biofilm compounds. The main aim of this study was to determine the anti‐biofilm properties of certain compounds and bacteriophages on F. psychrophilumbiofilms under static conditions using a standard 96‐well microtiter plate biofilm assay in vitro. Eight compounds (A‐type proanthocyanidins, D‐leucine, EDTA, emodin, fucoidan, L‐alliin, parthenolide, and 2‐aminoimidazole) at three sub‐minimum inhibitory concentrations (sub‐MICs), four bacteriophages (Fpv‐3, Fpv‐9, Fpv‐10, and Fpv‐21), and a phage combination (Fpv‐9 + Fpv‐10) were tested for inhibition of biofilm formation and reduction of the biomass of mature biofilms formed by two smooth isolates (P7‐9/10 and P1‐10B/10) and two rough isolates (P7‐9/2R/10 and P1‐10B/2R/10) of F. psychrophilum. The crystal violet staining method was used to stain the biofilms. Most of the compounds at sub‐MICs inhibited the biofilm formation of mainly smooth isolates, attaining up to 80% inhibition. Additionally, the same reduction trend was also observed for 2‐aminoimidazole, emodin, parthenolide, and D‐leucine on the biomass of mature biofilms in a concentration‐dependent manner. The anti‐biofilm properties of the compounds are believed to lie in their ability to disturb the cellular interactions during biofilm formation and probably to cause cell dispersal in already formed biofilms. Lytic bacteriophages efficiently inhibited biofilm formation of F. psychrophilum, while they partially reduced the biomass of mature biofilms. However, the phage combination (Fpv‐9 + Fpv‐10) showed a successful reduction in the biomass of F. psychrophilummature biofilms. We conclude that inhibiting compounds together with bacteriophages may supplement the use of disinfectants against bacterial biofilms (e.g., F. psychrophilumbiofilms), leading to a reduced occurrence of bacterial coldwater disease outbreaks at fish farms.

There is accumulated evidence supporting a beneficial role of Mediterranean diet (MD) in the control of asthma symptoms. The aim of this study was to investigate the relationships between adherence to MD and serum levels of certain cytokines namely, interleukin (IL)-4, and IL-17 known to have a pathogenetic role in the airway changes associated with asthma.

Background/Objectives: The aim of this work was to evaluate the current vitamin D status in healthy pregnant women and their newborns living in Greece and assess possible associations between 25(OH)D and anthropometric features of their fetuses and newborns. Materials & Methods: 81 healthy women were monitored during pregnancy. Biochemical markers related to bone metabolism, 25(OH)D and PTH levels were measured in serum samples of mothernewborn pairs at 1st trimester of pregnancy and at delivery in mothers, in cord blood and at the 3rd day of life of newborns. Results: Maternal 25(OH)D levels at the 1st trimester of pregnancy (22.6±9.2ng/ml) were significantly higher than those at delivery (19.2±9.2ng/ml) (p<0.001). Furthermore, umbilical 25(OH)D levels (21.3±9.3ng/ml) were higher than maternal at delivery (p=0.005) and neonatal levels (19.4±10.4 ng/ml) (p=0.021). Only 57.3% of the mothers at the first trimester and 46.7% at delivery as well as 55.8% of the fetuses and 38.5% of the neonates had adequate vitamin D levels (25(OH)D≥30ng/ml). A significant positive correlation was found between fetal femur length at the 22nd week of gestation and maternal 25(ΟΗ)D at the 1st trimester of pregnancy (r=0.36, p=0.048) while body length was significantly higher in newborns whose mothers had sufficient 25(OH)D levels (51.5±2.1cm) compared with those whose mothers had insufficient or deficient 25(OH)D levels at delivery (50.6±2.0cm) (p=0.047). Conclusion: The study confirms inadequate levels of vitamin D in pregnant women in Greece associated with inadequate vitamin D levels of their fetuses and newborns.

OBJECTIVE: Autosomal dominant hypocalcemia (ADH) is a rare familial or sporadic syndrome associated with activating mutations in the calcium sensing receptor (CaSR) gene. The aim of this study was to assess the functional significance of a novel CaSR mutation and, moreover, to present the clinical characteristics and the bone mineral density (BMD) progression from early childhood to late puberty in a patient with ADH. DESIGN: Genetic analysis of the CaSRgene was performed in a patient who presented in the neonatal period with hypocalcemic seizures and biochemical features of ADH. The functional impact of the novel mutation identified was assessed in cultured HEK 293T cells, transfected with either the wild type (WT) or mutant CaSR, by evaluating intracellular calcium ([Ca2+]i) influx after stimulation with extracellular calcium (Ca2+). Several BMD measurements were performed during the patient’s follow-up until late puberty. RESULTS: A novel CaSR mutation (p.L123S) was identified, which, as demonstrated by functional analysis, renders CaSR more sensitive to extracellular changes of Ca2+compared with the WT, although the difference is not statistically significant. BMD measurements, from early childhood to late puberty, revealed high normal to elevated BMD. CONCLUSION: We present the first Greek patient, to our knowledge, with sporadic ADH due to a novel gain-of-function mutation of the CaSRgene.

Supplemental Digital Content is available in the text.Wiskott-Aldrich syndrome (WAS) is a rare X-linked immunodeficiency characterized by various clinical phenotypes. We report the case of a 3-year-old immigrant boy presenting with persistent infant-onset thrombocytopenia treated for refractory immune thrombocytopenic purpura. Sequence analysis confirmed the diagnosis of WAS. The patient responded neither to IV infusions of immunoglobulin (Ig) nor a thrombopoietin receptor agonist and is currently planned for stem cell transplantation. Raised awareness is thus vital of this potentially misdiagnosed and lethal disorder. The diagnosis of WAS should be considered in all males with infant-onset immune thrombocytopenic purpura-like features, especially, if mean platelet volume is decreased (<7 fL) and good increment to platelet transfusions are evident.

Polymorphisms in the vitamin D receptor (VDR) gene have been studied in immune-related disorders either as independent contributors or in combination with vitamin D concentration. Vitamin D and VDR have been independently linked to asthma susceptibility. We investigated whether VDR variants were associated independently or in relation to vitamin D levels with asthma in Cypriot adolescents. We studied 190 current wheezers, 69 of which were categorized as active asthmatics and 671 healthy controls. We determined three VDR genotypes (BsmI, TaqI, ApaI) and measured serum 25(OH)D levels. Logistic regression and stratified analyses by the presence of hypovitaminosis D (≤20 ng/ml) were used to evaluate the association of the VDR variants with asthma. The distribution of TaqIgenotypes was significantly different between controls and current wheezers (p= 0.030) or active asthmatics (p= 0.014). The tt genotype was over-represented in wheezers (19.2 %) and asthmatics (21.3 %) compared to respective controls (12.9 %). No difference was observed between controls, current wheezers and active asthmatics in the genotypic distribution of BsmIand ApaIpolymorphic sites. After stratification by the presence of hypovitaminosis D, a significant association was detected between tt genotype of TaqIpolymorphism with wheezing (OR: 1.97, 95 % CI: 1.12, 3.46) and asthma (OR: 2.37, 95CI%: 1.02, 5.52) only in those with normal vitamin D levels (>20 ng/ml) but not in subjects with low vitamin D. The minor TaqIgenotype of VDR is associated with asthma in Cypriot adolescents. This polymorphism may contribute to asthma susceptibility primarily under conditions of normal vitamin D levels (>20 ng/ml).

Vitamin D has an indisputable immunodulatory role in both lung and immune system development, which is initiated during fetal life and is mainly accomplished in the first years of extrauterine life. Several published studies have shown that low levels of vitamin D may increase the risk of developing asthma and allergic diseases. Moreover, vitamin D deficiency epidemic reported over the last decades coincides with an increase in the prevalence of asthma and allergies in westernized societies. Since placental transfer of 25(OH)D is the major source of vitamin D in the developing fetus, important questions concerning the impact of maternal vitamin D status on the outcome of pregnancy have arisen. The aim of this review is to present the current evidence regarding the determinants of vitamin D status in pregnancy as well as its role in the development of asthma and allergies in early childhood.

In the present study, we aimed to assess bone status and the effect of gluten-free diet (GFD) in children with celiac disease (CD), and to evaluate the predictive value of standard serum biochemical indices in the diagnosis of bone mineral density (BMD) disturbances.

In the present study, we aimed to assess bone status and the effect of gluten-free diet (GFD) in children with celiac disease (CD), and to evaluate the predictive value of standard serum biochemical indices in the diagnosis of bone mineral density (BMD) disturbances. Forty-five children at the time of diagnosis of CD (group A, 77.8% girls) and 36 children receiving GFD for >2 years (group B, 75% girls) were included. Sixteen children in group A were reexamined 12 months after initiation of GFD. Serum measurements of biochemical bone health indices and BMD, assessed by dual x-ray absorptiometry, were obtained. Patients after 1 year of receiving GFD had higher BMD zscores compared with baseline (-1.45 ± 0.28 vs -0.61 ± 0.25, respectively, P= 0.004). BMD zscores were significantly lower than expected for the normal population, after 1 (P= 0.03) or at least 2 (P< 0.001) years of receiving GFD. In group B, BMD zscore was positively correlated with 25-hydroxy vitamin D levels (P= 0.009). In the repeated measurements group, 25-hydroxy vitamin D differed between pre- and post-GFD (P= 0.018). No biochemical index was capable of predicting an abnormal BMD zscore (receiver operating characteristic curve analysis, all of the areas under the curve <0.66). GFD has a beneficial effect on bone health. Two years receiving diet do not ensure normalization. Biochemical markers are not indicative of BMD disturbances. Dual x-ray absorptiometry should be included in the standard management of children with CD.

Oral anticoagulants antagonize vitamin K action and potentially impair the carboxylation of osteocalcin, a protein essential for normal bone matrix formation. In the present study, bone mineral density (BMD) and bone turnover markers were evaluated in 23 children under long-term oral anticoagulant therapy. BMD of the lumbar spine was assessed (Dual Energy x-ray Absorptiometry) and reported as zscore. Osteoblast bone alkaline phosphatase, osteocalcin (Gla-Oc), amino-terminal procollagen 1 extension peptide and osteoclast (urinary calcium and deoxypyridinoline, serum cross-linked C telopeptide) activity markers were measured. Vitamin D 25(OH) D, parathormone, calcium, phosphorus, magnesium and vitamin K status factors II, VII, IX, X, protein C, protein S, undercarboxylated osteocalcin (Glu-Oc) were determined. The above parameters were also evaluated in 25 healthy controls. Patients presented with higher levels in Glu-Oc, parathormone, and bone resorption markers, lower levels in bone formation markers and 25(OH) D, whereas 52 of them showed signs of osteopenia (−1> BMD zscore >−2.5). Statistical analysis demonstrated that anticoagulant therapy was an independent predictor of alterations in Glu-Oc, Gla-Oc, bone alkaline phosphatase, amino-terminal procollagen 1 extension peptide, and serum cross-linked C telopeptide levels. It seems that long-term use of coumarin derivatives may cause osteopenia in children with the risk of developing osteoporosis later in life.

AbstractBackground/Aims: Hypocalcemic vitamin D-resistant rickets (HVDRR) is a rare autosomal recessive disorder characterized by severe rickets, hypocalcemia, secondary hyperparathyroidism, elevated levels of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and occasionally, alopecia. In most cases, the disease is associated with mutations in the gene of the vitamin D receptor (VDR), the mediator of 1,25(OH)2D3 action. The apparently healthy HVDRR heterozygotes express both normal and mutant VDR alleles, and they present higher levels of 1,25(OH)2D3 than their respective controls. Because VDR function, except for the disease-causative mutations, might be influenced by the presence of certain polymorphisms, we investigated the distribution of four common VDR polymorphisms – BsmI, ApaI, TaqI and FokI – in HVDRR carriers compared with their respective controls. Methods: Sixty-seven relatives of 2 HVDRR patients, all members of an extended Greek kindred, were included in the study. VDR allelic polymorphisms were assessed by restriction fragment length polymorphisms after specific polymerase chain reaction amplification. Results: The distribution of genotypic and allelic frequencies differed between HVDRR carriers and their respective controls regarding BsmI and TaqI polymorphisms. The bb genotype and the T allele (presence of BsmI and absence of TaqI polymorphisms) were less frequent in the HVDRR carrier group than in the control group in a statistically significant manner (p = 0.029 and p = 0.025, respectively). Conclusions: Our findings showed that the apparently healthy HVDRR carriers present a different distribution of BsmI and TaqI VDR polymorphisms than their controls, suggesting that further investigation of the HVDRR carrier population may elucidate the implication of VDR alleles in VDR function and the vitamin D endocrine system.Copyright © 2007 S. Karger AG, Basel

AbstractBackground: Noonan syndrome (NS) (OMIM 163950) is an autosomal dominant developmental disorder characterized mainly by typical facial dysmorphism, growth retardation and variable congenital heart defects. In unrelated individuals with sporadic or familial NS, heterozygous missense point mutations in the gene PTPN11 (OMIM 176876) have been confirmed, with a clustering of mutations in exons 3 and 8, the mutation A922G (Asn308Asp) accounting for nearly 25% of cases. Patient and Methods: We report a 7-year-old boy with short stature and some other clinical features of NS, who has been investigated by molecular analysis for the presence of mutations in the PTPN11 gene. Result: The de novo mutation A172G in the exon 3 of the PTPN11 gene, predicting an Asn58Asp substitution, has been found. To the best of our knowledge, this specific mutation has only been described once before, but this is the first report of detailed clinical data suggesting a mild phenotype. Conclusion: Detailed clinical phenotype in every patient with major or minor features of NS and molecular identification of PTPN11 gene mutation may contribute to a better phenotype–genotype correlation.Copyright © 2006 S. Karger AG, Basel

Idiopathic Hypercalciuria (IH), a heterogenous disorder, is the most common cause of urolithiasis in children. IH patients present frequently with gross or microscopic hematuria, abdominal pain and a variety of urinary tract complaints (frequency-dysuria syndrome, enuresis, recurrent tract infection), with-noncalculus manifestation more prevalent than stone disease. Recently, osteopenia has been found in a high percentage of IH children even at the time of diagnosis. IH is characterized by urinary calcium excretion greater than 4mg/kg/day with normocalcemia in the absence of any other causes of hypercalciuria such as vitamin D intoxication, primary hyperparathyroidism, hyperthyroidism, immobilization, endogenous or exogenous glucocorticoid excess, distal renal tubular acidosis and furesemide medication. This complex metabolic disease is considered to be of genetic origin, as in some cases, it seems to be inherited in an autosomal dominant pattern. A variety of genes participating in the mechanisms of Ca homeostasis, have attracted the interest of researchers in order to elucidate the pathogenetic mechanism of the disease and thus determining the appropriate treatment for any distinct patient. However, no specific gene or polymorphisms are yet identified. Furthermore, studies on the pathophysiology of IH distinguish two prominent types of IH: the absorptive, characterized by increased intestinal Ca absorption, and the renal, characterized by decreased tubular Ca reabsorption. The distinction between renal and absorptive type could direct towards the better therapeutic protocol. Generally, the main goal of treatment applied on hypercalciuric children should be to alleviate and finally eliminate the symptoms of the disease, to prevent renal stone formation or recurrence and to permit the acquisition of the optimal bone mass. Initial management of those patients consists primarily of high fluid intake and dietary salt restriction. If the symptoms persist, thiazide diuretics prescription is ideal, especially for IH patients of renal type.

AbstractBackground/Aims: Hypocalcemic vitamin D-resistant rickets (HVDRR) is a rare monogenic autosomal recessive disorder associated with mutations in the gene of the vitamin D receptor (VDR), the mediator of 1,25(OH)2D3 action. Although many investigations have discussed the clinical manifestations and molecular etiology of this disease, only a few have investigated the biochemical and hormonal status of heterozygous HVDRR. The aim of the current work was to investigate the profile of selected biochemical and hormonal parameters related to the vitamin D endocrine system in a large number of HVDRR heterozygotes. Methods: 67 relatives of 2 HVDRR patients, all members of an extended Greek kindred of five generations with a common ancestor, were included in the study. Direct sequencing was used to identify VDR gene mutations. Serum Ca, P, 25(OH)D, iPTH, and 1,25(OH)2D levels were determined in all members of the kindred. Results: DNA analysis of the participants led to the design of two study groups: the HVDRR carriers (24) and the control subjects (43). Our results showed elevated circulating serum levels of 1,25(OH)2D3 and lower levels of PTH than their age- and sex-matched controls. No hypocalcemia or hypophosphatemia were detected in HVDRR carriers. Conclusions: Our findings suggest that HVDRR carriers may have compensatory elevated serum levels of 1,25(OH)2D3 through which they restrain PTH secretion. The study of HVDRR carriers could be a useful tool for the investigation of the vitamin D endocrine system.Copyright © 2006 S. Karger AG, Basel

The coding region determinant binding protein (CRD-BP) was isolated by virtue of its high affinity to the c-myc mRNA coding region stability determinant and shown to shield this message from nucleolytic attack, prolonging its half-life. CRD-BP is normally expressed during fetal life but is also activated de novo in tumors. Considering that aberrant CRD-BP expression may represent an additional mechanism interfering with c-myc regulation, we screened 118 primary breast carcinomas for CRD-BP expression, 60 of which had also been analyzed by comparative genomic hybridization (CGH). Copy number gains encompassing 8q24, the chromosome band that contains the c-myc locus, were detected in 48.3% (29/60) of tumors, whereas gains involving band 17q21, which contains the CRD-BP locus, were observed in 18.3% (11/60) of tumors. CRD-BP expression was detected in 58.5% (69/118) of tumors, implying mechanisms of activation alternative to gene amplification. Altogether, some 75% of the tumors had alterations pertaining to c-myc since they either harbored 8q24 gains and/or expressed CRD-BP. Significant associations were detected between CRD-BP expression and the absence of estrogen receptors (p = 0.005) and between the presence of 8q24 gains and an increased number of genomic changes as measured by CGH (p = 0.0017). Tumors were divided into 4 groups according to CRD-BP expression and 8q24 gains. The odds for tumors having both characteristics to be classified as poorly differentiated (grade III vs. grade I and II) were 19.6 times the corresponding odds for tumors neither expressing CRD-BP nor harboring 8q24 gains. For tumors either harboring 8q24 gains only or expressing CRD-BP alone, the corresponding odds were 6.4 and 3, respectively. © 2002 Wiley-Liss, Inc.

Congenital absence of breast development is a very rare abnormality. It may present as an isolated finding or it may be accompanied by other congenital anomalies. Here we report on a 13.5yearold girl presented to our pediatric endocrinology clinic because of lack of breast development. She had pubarche since the age of 10 years and was regularly menstruating since the age of 12 years. The patients medical history was positive for bilateral complete choanal atresia that was diagnosed and corrected soon after birth. Physical examination was unremarkable except for bilateral amazia, that is, absence of palpable breast tissue and hypoplastic areolae, whereas both nipples were formed. Renal ultrasonography and chest radiography were normal. The coexistence of congenital bilateral amazia and bilateral complete choanal atresia suggests that these rare disorders may be related etiologically. The patient is scheduled for breast augmentation. © 2009 WileyLiss, Inc.