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The black chokeberry, Aronia melanocarpa (Family Rosaceae), is native to North America and was introduced into Europe in the XIX century. Aronia melanocarpa contain particularly high amounts of procyanidins, anthocyanins, and phenolic acids. These antioxidants reduce the oxidative damage of human cells that can lead to cancer, heart disease, diabetes, hypertension, hypercholesterolemia. The black chokeberry may be used in the treatment and prevention of numerous civilization diseases.

Feeding disorders are common pediatric problems with diverse etiology. They are associated with organic diseases, especially digestive, circulatory and neurological conditions. Psychological factors may also play an important role. We present a case of infant admitted to hospital because of feeding disturbances and poor weight gain. Based on differential diagnostics we excluded organic causes of feeding disturbances in the presented case. Clinical observations and further events let us diagnose an incorrect mother–child relationship as possible reason of feeding disorder in our patient.

The results of 17 clinical trials on application L. plantarum 299v are presented in this review. According to them, it seems that usage of this strain is safe and could bring beneficial effects in treating patients with functional gastrointestinal disorders, infectious diarrhoea, recurrent C. difficile infection, acute pancreatitis, after liver transplantation and hospitalised in intensive care units. However, particular directions to usage of L. plantarum 299v in medical practice, especially in paediatrics, needs some further investigations performed on larger group of patients, also in developmental age.

Lesch-Nyhan syndrome is a rare inborn error of metabolism with very poor prognosis. Patients vary in many ways but all seem to have impairments to some degree in uric acid metabolism, motor development, and behavior. A careful evaluation is essential toward making the appropriate diagnosis. A case of infant with motor delay, spasticity, dystonia, and crystalluria is reported. Treatment based on allopurinal (12 mg/kg of body weight/24 h) reduced serum hyperuricemia to values

Introduction: Supermarkets together with their wide range of products are considered to be the major arenas of free choice of products. Marketing research has suggested that in-store environmental stimuli may induce substantial demand. A substantial body of research has determined that juice consumption is a risk factor of obesity among youth. Recently, research on dietary pattern increasingly focuses on the food environment. Unfortunately, there is a little data on exactly what infant food supermarkets stock. The greater share of the product on the shelf, the higher possibility to be chosen. Methods: In June 2012 we evaluated infant food aged 5–12 months in 6 supermarkets located in Warsaw. The methodology was based on tracking the information that consumer see when visiting a shop. We focused on four broad categories: porridges, dinner and dessert jars, fruit-based beverages, and infant tea. We analyzed the manufacturer and its offer of infant food, as well as length of shelves occupied by the broad categories of food. Results: The average length of shelves with fruit-based beverages and infant tea consisted 22% and 7% of total shelves length (porridges + jars + fruit-based beverages + tea), respectively. In 2 of 6 markets the length of shelves with juice and fruit drinks was higher than with porridges. The greatest offer of infant tea consisted of 29 types from 5 suppliers. Conclusions: This exploratory research allowed us to conclude that the space allocated to juice and fruit drinks is clearly larger than that recommended in dietary. In-store marketing cannot be ignored as having the critical influence on consumer behavior. From an academic point of view, there is a need for a continuous and careful study of relationship between infant food in-store marketing and nutritional guidelines.

Phenylketonuria is an inborn error of metabolism treated with a closely monitored low phenylalanine diet. Protein substitutes used for treatment are supplemented with vitamins and micronutrients.The aim of this study was to investigate plasma folic acid concentrations in children with phenylketonuria.Retrospective analysis of medical records of 73 patients with phenylketonuria and 28 with mild hyperphenylalaninemia (on normal diet) was carried out. Intake of folic acid was calculated on the basis of protein substitute intake. Folate concentrations were analyzed according to their intake, and concentration of homocysteine and phenylalanine.In 76.7% patients with phenylketonuria intake of folic acid exceeded recommended dietary allowance. Serum folic acid concentrations above upper reference level were detected in 75.3% patients with phenylketonuria and only in 25% patients with hyperphenylalaninemia (p0.0001). Strong positive correlation between daily intake of folic acid (with protein substitute) and concentration plasma folic acid (corr=0.55, p0.0001) has been observed.Low phenylalanine diet using protein substitutes currently available in Poland predisposes to high concentration of plasma folic acid. The security of folic acid hipersupplementation in patients with phenylketonuria requires further detailed research.

17p13.3 duplication is a rare and heterogeneous genetic syndrome. Microdeletions of this region are responsible for the symptoms of Miller-Dieker syndrome. We present a case of 17p13.3 duplication consisting of about 730kb in a patient with psychomotor developmental delay, concerning eye-hand coordination, posture, locomotion and speech. Among other symptoms, we found excessive physical development in relation to age, hypotonia, dysmorphic facial features (high and prominent forehead, low-set ears, hypertelorism, short nose, small upturned nose, narrow lips and pointed chin) and discrete changes in the CNS - enhanced frontal horns of the lateral ventricles and quite narrow corpus callosum. These symptoms overlap with phenotype of previously described patients with 17p13.3 duplication. The aberration has been identified by array comparative genomic hybridization (aCGH) and confirmed by fluorescence in situ hybridization (FISH). This publication presents a detailed, comparative characteristic of clinical fetures expression in discussed patient with 17p13.3 duplication and patients previously described in medical literature. Further cases with different variants of 17p13.3 duplication may contribute to characterise the specific genotypephenotype correlation.

OBJECTIVE: To evaluate dental arch relationship in preschoolers with unilateral cleft lip and palate after early alveolar bone grafting (ABG). MATERIALS AND METHODS: Three raters blindly assessed the dental arch relationship with the GOSLON Yardstick (using a 5-point scale, from 1--very good to 5--very poor outcome) in Early-grafted group (27 boys and 15 girls; mean age = 5.2 years, SD 0.5) and Non-grafted group (17 boys and 12 girls; mean age = 5.8 years, SD 0.8). The groups differed regarding the age when ABG was performed: between 2 and 4 years (mean = 2.4, SD 0.6) in the Early-grafted group and after 9 years in the Non-grafted group. The strength of agreement of rating was evaluated with kappa statistics. RESULTS: The intra- and inter-rater agreement was high (kappa > 0.800). The mean GOSLON score in the Early-grafted group was 2.72 and in the Non-grafted group -2.64. The distribution of the GOSLON grades in the Early-grafted group was: 54.8% had a score 1 or 2, 23.8%--3, and 21.4%--4 or 5; in the Non-grafted group, 38.0% subjects scored 1 or 2, 41.4%--3, and 20.6%--4 or 5 (p = 0.023). CONCLUSIONS: Early alveolar bone grafting carried out between the ages of 2 and 4 years was not found to negatively affect dental arch relationship by the age of 5 years. However, it is possible that such a negative effect could be found if a longer observation period (e.g. at age 10 years or age 15 years) was allowed.

Mostowska A, Hozyasz KK, Biedziak B, Wojcicka P, Lianeri M, Jagodzinski PP. Genotype and haplotype analysis of WNT genes in non-syndromic cleft lip with or without cleft palate. Eur J Oral Sci 2012; 120: 1–8. © 2012 Eur J Oral Sci The wingless-type MMTV integration site family (Wnt) signalling pathway plays a crucial role in craniofacial development. Recently, nucleotide variants in WNT genes have been shown to be associated with oral congenital anomalies, including facial clefts. Therefore, in the current study we decided to assay the association of nucleotide variants in selected WNT genes with the risk of non-syndromic cleft lip with or without cleft palate (NCL/P) in the Polish population. Fourteen polymorphisms in WNT3, WNT3A, WNT5A, WNT8A, WNT9B, and WNT11 were tested in a group of 210 patients with NCL/P and in a properly matched control group. The most significant results were found for the WNT3 rs3809857 variant, which, under the assumption of a recessive model, was associated with a two-fold decrease in the risk of NCL/P (ORTT vs. GT + GG = 0.492, 95% CI: 0.276–0.879, P = 0.015). Moreover, haplotype analysis revealed that WNT3 is significantly correlated with NCL/P. The global P-values for haplotypes of rs12452064_rs7207916 and rs3809857_rs12452064_rs7207916 were 0.0034 and 0.0014, respectively, and these results were statistically significant, even after the permutation test correction. In conclusion, our study confirmed the involvement of polymorphisms in the WNT3 gene in NCL/P aetiology in the tested population.

BACKGROUND Non-syndromic cleft lip and palate (CLP) is one of the most common birth defects. Recent genome-wide association studies (GWAS) have identified several novel risk loci associated with this craniofacial anomaly. Therefore, the objective of this report was to investigate the contribution of the top seven polymorphisms reaching genome-wide statistical significance in GWAS analyses in the Polish population. METHODS and RESULTS Nucleotide variants located at chromosomal regions 1p22.1, 10q25.3, 17q22, and 20q12 were tested in a group of 206 patients with nonsyndromic CLP and a properly matched control group. Significant results, which persisted even after Bonferroni correction (p < 0.0071), were observed for polymorphisms located at 10q25.3 (rs7078160 and rs4752028) and 17q22 (rs227731). Under a recessive model, both rs7078160 and rs4752028 were associated with a greater than fourfold increase in the risk of CLP (odds ratio [OR] = 4.536; 95% confidence interval [CI], 1.678–12.265; p = 0.0012 and OR = 4.573; 95% CI, 1.817–11.512; p = 0.0004, respectively). Polymorphism rs227731 increased the risk of CLP when analyzed under a dominant model (OR = 1.732; 95% CI, 0.184–2.253; p = 0.0044). Borderline association was alsoidentified for the 1p22.1 locus (rs481931). Moreover, 10q25.3 haplotypes were significantly associated with a susceptibility to CLP. CONCLUSION Our evaluation study confirmed a substantial association of polymorphisms located at chromosomal regions 10q25.3 and 17q22 with nonsyndromic CLP in the Polish population. Birth Defects Research (Part A), 2012. © 2011 Wiley Periodicals, Inc.

Celiac disease (CD) is a polygenic chronic enteropathy conferring an increased risk for various nutrient deficiency states. Hyperhomocysteinemia is a frequent finding in CD and may be related to the development of venous thrombosis, cardiovascular disease, and stroke in untreated CD patients. Recently, a possible excess in the frequency of the MTHFR c.677C>T (rs1801133) gene variant in CD patients was reported. The purpose of this study was to determine if there exist differences in the distribution of polymorphic variants of genes involved in homocysteine/methyl group metabolism between CD patients and the general population. A set of 10 gene polymorphisms (MTHFR rs1801133, MTR rs1805087, MTHFD1 rs2236225, MTRR rs1801394, CBS 844ins68, BHMT1 rs7356530 and rs3733890, BHMT2 rs526264 and rs625879, and TCN2 rs1801198) was tested in 134 patients with CD and 160 matched healthy controls. The frequency of the MTR rs1805087 GG genotype in CD patients was lower than in controls (0.01 and 0.06, respectively), although statistical significance was not achieved (P = 0.06). For the other analyzed polymorphisms, there was no evidence of difference in both allelic and genotypic distribution between cases and controls. The exhaustive Multifactor Dimensionality Reduction analysis revealed no combination of interactive polymorphisms predicting the incidence of CD. In contrast to the well-documented clinical observations of increased risks of vascular disease in patients with longstanding untreated CD, in our group of patients no significant association with CD was found for all tested polymorphic variants of genes involved in homocysteine metabolism. These findings should be replicated in studies with a larger sample size. Electronic supplementary material The online version of this article (doi:10.1007/s11033-011-1077-7) contains supplementary material, which is available to authorized users.

Orofacial clefts are thought to be determined by the interplay of genetic and environmental factors. Experiments on animals demonstrated that vitamin B12 supplemented diets antagonize selected teratogens during palatogenesis. Increased propionylcarnitine in neonates is regarded as a marker of maternal vitamin B12 deficiency. The retrospective study was undertaken to determine whether increased propionylcarnitine in newborns is associated with orofacial clefts. Fifty-two newborns with isolated cleft lip with or without cleft palate (CLP) and 107 control newborns without congenital anomalies were investigated. Whole blood propionylcarnitine concentrations were measured using tandem mass spectrometry. The mean concentrations of propionylcarnitine in newborns with clefts and controls were 2.82 ± 1.06 µmol L−1 and 2.68 ± 0.94 µmol L−1, respectively. T-test for equality of means did not confirm any significant differences between both groups (P = 0.381). Deficiency of vitamin B12 with metabolic disturbances seems not to be a risk factor for CLP in the investigated group of patients.

Non-syndromic cleft lip with or without cleft palate (CL/P) has severe long-lasting adverse effects on both physical and psychological development. Although recent years have brought significant improvement in clinical treatment, our understanding of the etiology of this congenital anomaly is lagging. Many genes, genetic pathways, harmful exposures, as well as nutrient deficiencies have been implicated in abnormal palatogenesis. Extrapolating data regarding risk factors for CL/P from different populations is not always straightforward. This review gives an overview of knowledge about both environmental and genetic risk factors in the etiology of CL/P in the Polish population, which was originally presented in research papers by the author and collaborating investigators. The findings suggest a possible association between maternal consumption of α-tocopherol, retinol, zinc, citrulline, and dietary compounds contributing to methyl-group homeostasis and CL/P risk. Polymorphisms in BHMT1 and BHMT2 were significantly associated with decreased CL/P risk in the Polish population. Other interesting findings include associations of CL/P risk with polymorphisms in MTR, PCYT1A, ASS1, SLC 25A13, GSTM1, GSTT1, SUMO1 genes, and 8q24.21 loci. Reviewed research papers indicate interesting pathways and new candidate genes for further investigation, and partly confirm earlier findings according risk factors for orofacial clefts.

Objective Maternal mid-pregnancy low levels of symmetric dimethylarginine and newborn low levels of citrulline are suspected to be risk factors for orofacial clefts. This study was undertaken to investigate the involvement of polymorphic variants of genes related to arginine metabolism in the susceptibility of clefting. Design PCR-RFLP and HRM analyses were used to analyze single nucleotide polymorphisms (SNPs) of ASS1, ASL, and SLC25A13 in 172 children with non-syndromic cleft lip with or without cleft palate (CL/P) and 188 controls without congenital anomalies. The differences in allele and genotype frequencies between cases and controls were determined using standard Chi-square and Fisher exact tests. The odds ratio (OR) and associated 95% confidence intervals (95% CI) for individuals with CL/P versus controls were also calculated. Associations between the investigated polymorphisms and the risk of being born with an orofacial cleft were tested using the nonparametric and genetic model-free Multifactor Dimensionality Reduction (MDR) approach. Results Analysis of five SNPs of the ASS1 gene revealed that the G allele of rs7860909 is associated with increased CL/P risk. Compared to individuals with the AA genotype, the G allele carriers had an OR of 1.768 (95% CI: 1.133–2.759; p = 0.012). For the remaining SNPs of all analysed genes, there was no overall evidence for cleft association considering the allele and genotype distribution. However, gene-by-gene interaction analysis conducted using the MDR approach revealed a significant interactive genetic effect of ASS1 (rs666174) and SLC25A13 (rs10252573) on the occurrence of clefting (p = 0.002). Conclusion Our results demonstrate moderate evidence for the association of polymorphic variants of genes related to arginine metabolism with abnormal palatogenesis.

The Mediterranean diet is well known for its health-promoting effects. Among its key ingredients, olive oil is the most characteristic. Processing industries have been successfully manufacturing and marketing jarred baby foods with the use of vegetable oils, including olive oil, as well as other sources of visible fat. We aimed to survey manufacturer claims concerning added fat in jarred infant foods supplied to the Polish market. A total of 124 kinds of infant foods from six suppliers were analyzed. Corn, canola, and soybean oil occupied the first three positions, respectively, in rank order of vegetable oils used in jarred baby foods. In our sample, only one type of ready-to-eat jars with vegetables contained olive oil. 11% of products contained cow milk butter or cream. 61% of jarred “dinners” contained poultry or fish, which are typical sources of animal protein in the Mediterranean diet. Given that commercial baby foods currently available in the Polish market contain no olive oil, we advocate considering home preparation of infant foods with the use of visible fat. Medical professionals should encourage food manufacturers to return to the concepts of the Mediterranean diet for young consumers, aimed at long-term health.

Mostowska A, Hozyasz KK, Biedziak B, Misiak J, Jagodzinski PP. Polymorphisms located in the region containingBHMTandBHMT2genes as maternal protective factors for orofacial clefts. Eur J Oral Sci 2010; 118: 325–332. © 2010 The Authors. Journal compilation © 2010 Eur J Oral Sci Nonsyndromic cleft lip with or without cleft palate (NCL/P) is one of the most common craniofacial malformations; however, its aetiology is still unclear. Because the effects of maternal nutrition on fetal development are well known, we decided to pursue the question of whether polymorphic variants of genes encoding enzymes involved in choline metabolism might be associated with the maternal risk of having a baby with NCL/P. Analysis of 18 single nucleotide polymorphisms (SNPs) of betaine-homocysteine methyltransferase (BHMT), betaine-homocysteine methyltransferase-2 (BHMT2), choline dehydrogenase (CHDH), choline kinase (CHKA), dimethylglycine dehydrogenase (DMGDH), choline-phosphate cytidylyltransferase A (PCYT1A), and phosphatidylethanolamine N-methyltransferase (PEMT) provided evidence that polymorphisms located in the region containing BHMT and BHMT2 were protective factors against NCL/P affected pregnancies in our population. The strongest signal was found for the SNP located in the intronic sequence of BHMT2. Women carrying two copies of the rs625879 T allele had a significantly decreased risk of having offspring with orofacial clefts. These results were significant, even after correction for multiple comparisons. Moreover, the gene–gene interaction analysis revealed a significant epistatic interaction of BHMT2 (rs673752), PEMT (rs12325817), and PCYT1A (rs712012) with maternal NCL/P susceptibility. Altogether, our study identified a novel gene, the nucleotide variants of which were be associated with a decreased risk of having a baby with NCL/P.

Streszczenie Wstep Metabolity talidomidu, np. pochodne kwasu glutarowego, dzialają teratogennie. Zwiekszone wytwarzanie kwasu glutarowego skutkuje wzrostem stezenia glutarylkarnityny (C5DC). W badaniu przesiewowym noworodkow w kierunku kwasicy glutarowej są wykorzystywane oznaczenia C5DC. Cel Celem pracy byla analiza stezenia C5DC u dzieci z rozszczepami twarzoczaszki. Metody Retrospektywnie analizowano wyniki oznaczen C5DC w badaniach przesiewowych noworodkow metodą tandemowej spektrometrii mas (MS/MS). Grupe badaną stanowilo 51 pacjentow z izolowanym rozszczepem wargi polączonym lub nie z rozszczepem podniebienia. Do grupy kontrolnej zakwalifikowano 107 zdrowych dzieci bez wad wrodzonych. W analizie statystycznej wykorzystano testy sumy rang Wilcoxona i χ 2 . Wyniki Stezenia glutarylkarnityny (mediana; IQR) byly istotnie statystycznie wieksze u noworodkow z rozszczepem twarzoczaszki w porownaniu z noworodkami bez wad wrodzonych; 0,062 (0,044–0,083) μ mol/l vs 0,045 (0,034–0,067) μ mol/l, p=0,001. U dzieci z wadą nie stwierdzono wystepowania stezenia C5DC mniejszego od 5 centyla w grupie kontrolnej. Wniosek Uzyskane wyniki sugerują zaleznośc pomiedzy homeostazą kwasu glutarowego a palatogenezą.

Maternal zinc deficiency seems to be a risk factor for orofacial clefts in offspring. This study was undertaken to investigate the involvement of polymorphic variants of genes for zinc transporters in the susceptibility of clefting. PCRRFLP analysis was used to analyze single nucleotide polymorphisms of SLC30A1 (rs7526700, rs2278651, rs611386), SLC30A4 (rs2453531, rs8029246), SLC30A5 (rs351444, rs164393, rs6886492), SLC39A1 (rs10127484, rs11264736), and SLC39A3 (rs759071, rs4806874, rs10415622) in mothers of children with non-syndromic cleft lip with or without cleft palate (CL/P) and control mothers. The allele, genotype, and haplotype distribution was found to be similar among case and control mothers. Also, the gene-by-gene interaction analysis conducted using the Multifactor Dimensionality Reduction approach revealed no significant interactive genetic effect on having a child with a cleft. In conclusion, our results demonstrated that the analyzed polymorphic variants of genes for zinc transporters are not implicated in abnormal palatogenesis in the investigated group of women from the Polish population.

Background Non-syndromic isolated cleft lip with or without cleft palate (NCL/P) is a common congenital anomaly in humans, the aetiology of which is complex and associated with both genetic and environmental factors. It has been reported that maternal nutritional factors are likely to play a major role in development of NCL/P in the embryo. Objective As the mechanism by which folic acid and choline supplementation prevents NCL/P is poorly understood, the relationship between 16 polymorphic variants of 12 genes encoding enzymes involved in the metabolism of these two nutrients and the risk of facial clefts was investigated. Results It was found that individuals with the AA genotype of the BHMT rs3733890 polymorphism have a significantly lower risk of orofacial clefts (OR 0.1450, 95% CI 0.0420 to 0.4995; p=0.0005; p corr =0.008). It was also demonstrated that the rs7639752 polymorphism of the PCYT1A gene increases the risk of NCL/P nearly twofold in the Polish population (OR 1.891, 95% CI 1.151 to 3.107; p=0.011), but this association would not withstand correction for multiple testing (p corr =0.176). The genetic variations in CBS , MTHFD1 , MTHFR , MTR , MTRR , TCN2 , BHMT2 , CHDH , CHKA , and PEMT were not separately correlated with NCL/P risk. However, the Multifactor Dimensionality Reduction (MDR) analysis showed a significant epistatic interaction between MTHFR (rs1801133), MTR (rs1805087), and PEMT (rs4646406) in NCL/P susceptibility. Conclusion This study demonstrates that choline metabolism may play an important role in the aetiology of NCL/P. Polymorphic variants of BHMT and PCYT1A and interactions between genes of choline and folate metabolism might influence the risk of NCL/P in the Polish population.

Streszczenie W pracy przedstawiono historie obecności bananow w diecie ludzi oraz wyniki najnowszych badan dotyczących stosowania diety bananowej w leczeniu biegunki i niedozywienia. Bogate piśmiennictwo sugeruje takze znaczenie bananow w zapobieganiu nowotworom, chorobom ukladu krązenia oraz hipokalimii.

Objective: The study focused on the correlation between maternal polymorphisms of genes encoding antioxidant enzymes and the risk of having a child with CL/P in the Polish population. Method: PCR–RFLP analysis was used to analyze polymorphisms of MnSOD 2 (c.47T>C), CAT (c.− 330C>T) and GPX1 (c.599C>T) in mothers of children with CL/P and control mothers. Results and Conclusion: Polymorphic variants of genes for main antioxidant enzymes were determined not to be a maternal risk factor for having a child with CL/P in the investigated group of women.

The locus on chromosome 15q13.3 containing GREM1 is correlated with the risk of nonsyndromic cleft lip with or without cleft palate (NSCL/P). The aim of the present study was to find the GREM1 functional variants implicated in the aetiology of this common developmental anomaly in the Polish population.Eight polymorphisms were genotyped in 334 NSCL/P patients and 955 controls. In addition, the GREM1 protein-coding region was sequenced in 96 NSCL/P patients.Significant association with a risk of oral clefts was found for 5 tested polymorphisms. The lowest p(trend) values were identified for rs16969681, rs16969816, and rs1258763 (p(trend) 4.09E-05, 3.35E-05, and 0.0002, respectively). The putative functional variant rs16969681, located in a region that has enhancer activity, was associated with a 2.6-fold lower risk for NSCL/P (odds ratio [OR] = 0.38; 95% confidence interval [CI], 0.24-0.61, p = 2.37E-05). The previously reported association of rs1258763 with NSCL/P was replicated (OR = 0.57; 95% CI, 0.44-0.73; p = 1.10E-05). For all tested GREM1 variants, no significant sex-by-genotype interaction effects were observed. The sequencing analysis did not detect any rare variants implicated in the development of oral clefts.Our results might suggest that variants influencing GREM1 expression levels, rather than variants affecting the function of the encoded protein, are significant factors in NSCL/P etiology.

The aetiology of non-syndromic cleft lip with or without cleft palate (CL/P) is very complex. It has been shown that polymorphic variants of genes encoding key proteins of folate and methionine metabolism might be important maternal risk factors of having a child with this craniofacial anomaly. Therefore, in our study, mothers with CL/P children as well as control mothers were examined for prevalence of polymorphisms of genes that encode methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formylte-trahydrofolate synthetase (MTHFD1) and reduced folate carrier 1 (RFC1). We observed that there were no statistical differences in allele and genotype frequencies of MTHFR c.677C>T, MTHFD1 c.1958G>A and RFC1 c.80G>A between mothers who had children with CL/P and control mothers. However, mothers with MTR c.2756AG or GG genotype displayed a 2.195-fold increased risk of having a child with CL/P (95% CI 1.189-4.050, p = 0.011). The mechanism by which polymorphic transition of MTR gene might increase the maternal risk of having CL/P progeny is unknown. Our observations are consistent with a significant role of the methyl cycle in the development of craniofacial structures in humans.

Achieving a successful and well-functioning reconstruction of craniofacial deformities still remains a challenge. As for now, autologous bone grafting remains the gold standard for alveolar cleft reconstruction. However, its aesthetic and functional results often remain unsatisfactory, which carries a long-term psychosocial and medical sequelae. Therefore, searching for novel therapeutic approaches is strongly indicated. With the recent advances in stem cell research, cell-based tissue engineering strategies move from the bench to the patients' bedside. Successful stem cell engineering employs a carefully selected stem cell source, a biodegradable scaffold with osteoconductive and osteoinductive properties, as well as an addition of growth factors or cytokines to enhance osteogenesis. This review highlights recent advances in mesenchymal stem cell tissue engineering, discusses animal models and case reports of stem cell enhanced bone regeneration, as well as ongoing clinical trials.

INTRODUCTION: Hypospadias has a complex etiology with both genetic and environmental factors contributing to the condition. Urogenital abnormalities including hypospadias, are found in 22% of cases with Ellis van Creveld syndrome (EvC). Mutations in the EVC gene can cause major and minor anomalies, which form phenotypes that partially overlap with those present in EvC. The aim of this study was to evaluate the association between nucleotide variants of the EVC gene and the risk of hypospadias. MATERIAL AND METHODS: Four single nucleotide polymorphisms (SNPs) of the EVC gene (rs3774856, rs2302075, rs1383180, rs7680768) were taken under investigation in 96 patients with isolated hypospadias and 284 matched controls. Genotyping of all polymorphisms was carried out by PCR and followed by appropriate restriction enzyme digestion (PCR-RFLP). RESULTS: Individuals homozygous for the SNP rs2302075 (p.Thr449Lys) showed an elevated risk for hypospadias. Haplotypes containing the rs2302075 variant also revealed modest associations with hypospadias, which did not survive multiple testing corrections. None of the other tested EVC polymorphisms displayed significant association with the risk of hypospadias, either in dominant or recessive inheritance models. CONCLUSIONS: The results of this study suggest that polymorphic variants of the EVC gene do not substantially contribute to the risk of hypospadias based on our study population. However, further studies should help to clarify the relationship between polymorphisms of EVC and hypospadias.

The etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P) is very complex and still not well elucidated. Given the critical role of DNA damage repair in the embryonic development, we decided to test the hypothesis that polymorphisms of selected DNA repair genes might contribute to the risk of NSCL/P in the Polish population.Analysis of 36 polymorphisms in 12 DNA damage repair genes (ATM, BLM, BRCA1, BRIP1, E2F1, MLH1, MRE11A, MSH2, MSH6, NBN, RAD50, and RAD51) was conducted using TaqMan assays in a group of 263 NSCL/P patients and matched control group (n = 526).Statistical analysis of genotyping results revealed that nucleotide variants in the BRIP1 (BACH1) gene were associated with the risk of NSCL/P. Under assumption of a dominant model, the calculated odds ratios (ORs) for BRIP1 rs8075370 and rs9897121 were 1.689 (95% confidence interval [CI], 1.249-2.282; p = 0.0006) and 1.621 (95% CI, 1.200-2.191; p = 0.0016), respectively. These results were statistically significant even after applying multiple testing correction. Additional evidence for a causative role of BRIP1 in NSCL/P etiology was provided by haplotype analysis. Borderline association with a decreased risk of this anomaly was also observed for BLM rs401549 (ORrecessive = 0.406; 95% CI, 0.223-1.739; p = 0.002) and E2F1 rs2071054 (ORdominant = 0.632; 95% CI, 0.469-0.852; p = 0.003).Our study suggests that polymorphic variants of DNA damage repair genes play a role in the susceptibility to NSCL/P. BRIP1 might be novel candidate gene for this common developmental anomaly.

Do niedawna metabolizm nie-bialkowego aminokwasu cytruliny nie cieszyl sie zainteresowaniem badaczy. Synteza cytruliny de novo ma miejsce w enterocytach, a jej stezenia są uwazane za marker prawidlowej czynności jelita cienkiego. Stezenie cytruliny w pelnej krwi u nowo diagnozowanych chorych na celiakie jest male. U osob genetycznie usposobionych do rozwoju celiakii gliadyna moze uszkadzac plodową i matczyną cześc lozyska. Male stezenia cytruliny we krwi po urodzeniu moglyby odzwierciedlac niekorzystne dzialanie gliadyny rowniez na jelito cienkie. Retrospektywna analiza wykazala prawidlowe stezenia cytruliny w przesiewowym badaniu noworodkow u dwojga dzieci ze zdiagnozowaną celiakią oraz u potomstwa kobiety z zaniedbaną celiakią. Przedstawione przypadki kliniczne nie sugerują, ze oznaczenia stezenia cytruliny w pelnej krwi z badania przesiewowego noworodkow mają wartośc prognostyczną w ocenie ryzyka rozwoju celiakii.

Cystynuria jest chorobą metaboliczną, w ktorej zaburzony jest nerkowy i jelitowy transport aminokwasow dwuzasadowych. Z powodu malej rozpuszczalności cystyny w moczu latwo tworzą sie zlogi z tego aminokwasu. Procesowi krystalizacji moze zapobiegac odpowiednie nawodnienie oraz modyfikacja diety chorego. W ostatnich latach w terapii kamicy cystynowej stosuje sie kaptopryl. Lek ten m.in. wykazuje aktywnośc przeciwutleniającą. Celem pracy bylo zbadanie calkowitej aktywności przeciwutleniającej osocza (TAS) u chorych na cystynurie. Material i metody Badaniem objeto 11 chorych z nawracającą kamicą cystynową. Grupa kontrolna liczyla 18 zdrowych dzieci. Pomiary TAS w osoczu wykonano metodą kolorymetryczną. Wyniki U chorych średni poziom TAS byl istotnie statystycznie mniejszy (1,21 ± 0,06 mmol/l) niz w grupie kontrolnej (1,29 ± 0,06 mmol/l, p Wniosek Zaburzenia rownowagi antyoksydacyjnej mogą byc powiązane z klinicznym obrazem cystynurii.

Z powodu szerokiego zakresu objawow klinicznych wiele przypadkow celiakii pozostaje nierozpoznanych. W pracy przedstawiono piecioro dzieci z celiakią i niedoborem wysokości ciala jako jedyną nieprawidlowością w badaniu przedmiotowym. U wszystkich chorych morfologia i aktywnośc aminotransferazy alaninowej w surowicy krwi mieścily sie w zakresie wartości prawidlowych. Obserwacja ta potwierdza pogląd, ze nie ma jednego uniwersalnego parametru wśrod podstawowych badan laboratoryjnych, ktory moglby sugerowac obecnośc choroby trzewnej u niskoroslych dzieci.

Background Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common structural malformation with a complex and multifactorial aetiology. Associations of abnormalities in phenylalanine metabolism and orofacial clefts have been suggested. Methods Eight single nucleotide polymorphisms (SNPs) of genes encoding phenylalanine hydroxylase (PAH) and large neutral l -amino acid transporter type 1 (LAT1), as well as the PAH mutation that is most common in the Polish population (rs5030858; R408W), were investigated in 263 patients with NSCL/P and 270 matched controls using high resolution melting curve analysis (HRM). Results We found that two polymorphic variants of PAH appear to be risk factors for NSCL/P. The odds ratio (OR) for individuals with the rs7485331 A allele (AC or AA) compared to CC homozygotes was 0.616 (95% confidence interval [CI] = 0.437–0.868; p = 0.005) and this association remains statistically significant after multiple testing correction. The PAH rs12425434, previously associated with schizophrenia, was borderline associated with orofacial clefts. Moreover, haplotype analysis of polymorphisms in the PAH gene revealed a 4-marker combination that was significantly associated with NSCL/P. The global p -value for a haplotype comprised of SNPs rs74385331, rs12425434, rs1722392, and the mutation rs5030858 was 0.032, but this association did not survive multiple testing correction. Conclusion This study suggests the involvement of the PAH gene in the aetiology of NSCL/P in the tested population. Further replication will be required in separate cohorts to confirm the consistency of the observed association.

Item does not contain fulltext BACKGROUND/PURPOSE: In mice, biotin deficiency is one of the most potent clefting factors. Increased 3-hydroxyisovalerylcarnitine (C5OH) is regarded as a biomarker of biotin deficiency. This retrospective study was undertaken to determine whether increased C5OH in newborns is associated with orofacial clefts. MATERIALS AND METHODS: Seventy newborns with non-syndromic cleft lip with or without cleft palate and 140 control newborns without congenital anomalies were investigated. Whole-blood C5OH concentrations were measured using tandem mass spectrometry. RESULTS: The median (interquartile range, IQR) concentrations of C5OH in patients with clefts and controls were 0.16 (0.13-0.22)mumoll(-1) and 0.17 (0.13-0.20)mumoll(-1), respectively (p=0.90). The receiver operating characteristic analysis did not find out cut-off values for C5OH discriminating between cases and controls. CONCLUSION: There appears to be no association between biotin deficiency, as indexed by an increase of C5OH, and orofacial clefts in the investigated group of patients.

Orofacial clefts are among the most common birth defects and result in an improper formation of the mouth or the roof of the mouth. Monosomy of the distal aspect of human chromosome 6p has been recognized as causative in congenital malformations affecting the brain and cranial skeleton including orofacial clefts. Among the genes located in this region is PAK1IP1, which encodes a nucleolar factor involved in ribosomal stress response. Here, we report the identification of a novel mouse line that carries a point mutation in the Pak1ip1 gene. Homozygous mutants show severe developmental defects of the brain and craniofacial skeleton, including a median orofacial cleft. We recovered this line of mice in a forward genetic screen and named the allele manta-ray (mray). Our findings prompted us to examine human cases of orofacial clefting for mutations in the PAK1IP1 gene or association with the locus. No deleterious variants in the PAK1IP1 gene coding region were recognized, however, we identified a borderline association effect for SNP rs494723 suggesting a possible role for the PAK1IP1 gene in human orofacial clefting.

The wingless-type MMTV integration site family (Wnt) signalling pathway plays a crucial role in craniofacial development. Recently, nucleotide variants in WNT genes have been shown to be associated with oral congenital anomalies, including facial clefts. Therefore, in the current study we decided to assay the association of nucleotide variants in selected WNT genes with the risk of non-syndromic cleft lip with or without cleft palate (NCL/P) in the Polish population. Fourteen polymorphisms in WNT3, WNT3A, WNT5A, WNT8A, WNT9B, and WNT11 were tested in a group of 210 patients with NCL/P and in a properly matched control group. The most significant results were found for the WNT3 rs3809857 variant, which, under the assumption of a recessive model, was associated with a two-fold decrease in the risk of NCL/P (OR(TT vs. GT + GG) = 0.492, 95% CI: 0.276-0.879, P = 0.015). Moreover, haplotype analysis revealed that WNT3 is significantly correlated with NCL/P. The global P-values for haplotypes of rs12452064_rs7207916 and rs3809857_rs12452064_rs7207916 were 0.0034 and 0.0014, respectively, and these results were statistically significant, even after the permutation test correction. In conclusion, our study confirmed the involvement of polymorphisms in the WNT3 gene in NCL/P aetiology in the tested population.

Item does not contain fulltext The objective of this study was to evaluate the association between nasolabial symmetry and aesthetics in children with complete unilateral cleft lip and palate (CUCLP). Frontal and basal photographs of 60 consecutively treated children with CUCLP (cleft group: 41 boys and 19 girls, mean (SD) age 11 (2) years) and 44 children without clefts (control group: 16 boys and 28 girls, mean (SD) age 11(2) years), were used for evaluation of nasolabial symmetry and aesthetics. Nasal and labial measurements were made to calculate the coefficient of asymmetry (CA). The 5-grade aesthetic index described by Asher-McDade et al. was used to evaluate nasolabial appearance. Correlation and regression analysis were used to identify an association between aesthetics and CA, sex, and the presence of CUCLP. Ten measurements in the cleft, and 2 in the control, group differed significantly between the cleft and non-cleft (or right and left) sides, respectively. The significantly higher values of 9 of 11 CA in the children with CUCLP indicated that they had more asymmetrical nasolabial areas than children without clefts. However, the regression analyses showed that only a few CA were associated with nasolabial aesthetics. In conclusion, nasolabial aesthetics and nasolabial symmetry seem to be only weakly associated in patients with CUCLP.

Malonyl-CoA is regarded as a key signaling molecule in mammalian cells. It is converted to acetyl-CoA, and to a lesser extent, to malonyl acid and malonylcarnitine (C3DC). Availability of carnitine has been reported to be essential for the developing fetus. The objectives of the present study were to analyze associations of malonylcarnitine, acetylcarnitine (C2), and free carnitine (CO) in subjects with orofacial clefts.We performed a retrospective analysis of carnitine concentration obtained from a newborn screening program carried out in our institution. Concentrations of whole blood malonylcarnitine, acetylcarnitine, and free carnitine were measured using tandem mass spectrometry. The study group consisted of 51 children with nonsyndromic cleft lip with or without cleft palate. In total, 106 healthy children without congenital anomalies served as controls. Cut-off points were established using likelihood ratio values.The mean concentration of malonylcarnitine in the cleft group was lower than that of the control group, 0.048 micromol x L(-1) vs. 0.058 micromol x L(-1), respectively (P = 0.009). In patients with orofacial cleft, low malonylcarnitine levels (or = 0.047 micromol x L(-1)) were 1.7 times more predominant than in healthy individuals (P = -0.03). The mean concentration of acetylcarnitine was also lower in affected newborns in comparison to controls, 33.8 micromol x L(-1) vs. 37.8 micromol x L(-1), respectively (P = 0.026). After analysis of acetylcarnitine and free carnitine concentrations, the likelihood ratio test did not indicate valuable cut-offpoints.The study provides initial data indicating a potential association between decreased malonylcarnitine and abnormal palatogenesis.

BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (NCL/P) is a common structural malformation with a complex and multifactorial etiology. It has been shown that maternal psychological stress in the periconceptional period can contribute to an increase in the risk of NCL/P affecting pregnancy. METHODS: Twenty-four single nucleotide polymorphisms of 11 stress-related genes (COMT, CRHR1, FKBP5, GABRA6, HSD11β2, MAOA, NPY, NR3C1, SERPINA6, SLC6A4, and TPH2) were investigated in 220 healthy mothers of children with facial clefts and 210 matched controls using restriction fragment-length polymorphism and high-resolution melting analysis. RESULTS: We found that polymorphisms in SLC6A4, TPH2, and SERPINA6 appear to be maternal factors increasing the risk of having a child with facial clefts. The closest correlations with NCL/P were found for the SLC6A4 rs2020942 and TPH2 rs10879357 gene variants (odds ratio [OR], 1.720; 95% confidence interval [CI], 1.158–2.553; p = 0.0069; ptrend = 0.0036; and OR, 1.837; 95% CI, 1.226–2.753, p = 0.0030, ptrend = 0.0057; respectively). Moreover, haplotype analysis revealed that several combinations of markers in SLC6A4, TPH2, and SERPINA6 might be significantly associated with the risk of NCL/P affected pregnancies. However, these associations were not statistically significant after correction for multiple testing. CONCLUSION: This study suggests that nucleotide variants of genes encoding components of the hypothalamus-pituitary-adrenal axis and serotoninergic system have a role in the etiology of NCL/P in the Polish population. SLC6A4, TPH2, and SERPINA6 might be novel candidate genes for this common congenital anomaly. Birth Defects Research (Part A), 2011. © 2011 Wiley-Liss, Inc.

Nonsyndromic cleft lip with or without cleft palate (NCL/P) is one of the most common craniofacial malformations; however, its aetiology is still unclear. Because the effects of maternal nutrition on fetal development are well known, we decided to pursue the question of whether polymorphic variants of genes encoding enzymes involved in choline metabolism might be associated with the maternal risk of having a baby with NCL/P. Analysis of 18 single nucleotide polymorphisms (SNPs) of betaine-homocysteine methyltransferase (BHMT), betaine-homocysteine methyltransferase-2 (BHMT2), choline dehydrogenase (CHDH), choline kinase (CHKA), dimethylglycine dehydrogenase (DMGDH), choline-phosphate cytidylyltransferase A (PCYT1A), and phosphatidylethanolamine N-methyltransferase (PEMT) provided evidence that polymorphisms located in the region containing BHMT and BHMT2 were protective factors against NCL/P affected pregnancies in our population. The strongest signal was found for the SNP located in the intronic sequence of BHMT2. Women carrying two copies of the rs625879 T allele had a significantly decreased risk of having offspring with orofacial clefts. These results were significant, even after correction for multiple comparisons. Moreover, the gene-gene interaction analysis revealed a significant epistatic interaction of BHMT2 (rs673752), PEMT (rs12325817), and PCYT1A (rs712012) with maternal NCL/P susceptibility. Altogether, our study identified a novel gene, the nucleotide variants of which were be associated with a decreased risk of having a baby with NCL/P.

BACKGROUND Cleft lip with or without cleft palate (CL/P) is one of the most common craniofacial malformations, with a complex and multifactorial etiology. Because of the genetic heterogeneity of facial clefts, the aim of this study was to investigate the contribution of previously reported candidate genes and chromosomal loci to the risk of CL/P in the Polish population. METHODS We performed an analysis of 18 polymorphisms of FOXE1, IRF6, MSX1, PAX9, TBX10, FGF10, FGFR1, TGFα, TGFβ3, SUMO1, and the chromosomal region 8q24 in a group of 175 patients with CL/P and a properly matched control group. RESULTS Highly significant results were observed for the IRF6 rs642961 variant and the 8q24 region's rs987525 (odds ratio [OR]AG+AAvsGG, 1.635; 95% confidence interval [CI], 1.153–2.319; p = 0.005; and ORAC+AAvsCC, 1.962; 95% CI, 1.382–2.785; p = 1.4 × 10−4, respectively). For rs987525, the results were also significant after correction for multiple comparisons. Borderline association with an increased risk of CL/P was also identified for the SUMO1 locus (rs2350350; ORCGvsGG, 1.580; 95% CI, 1.056–2.363; p = 0.025). CONCLUSIONS Our findings confirmed that genetic variants of IRF6 and the polymorphism located in the 8q24 gene desert are strongly involved in the etiology of facial clefts in the Polish population sample. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc.

The amino acid citrulline is poorly represented in food, except for the Cucurbitaceae family of fruits (watermelons, etc.) and sap from birch trees, which have both been used in the treatment of reproductive disorders for centuries. Recently, an interesting observation was published regarding citrulline as a promising candidate biomarker of abnormal embryogenesis. Our study was undertaken to investigate the involvement of newborn citrulline concentrations as potential risk factors for orofacial clefting. We performed a retrospective analysis of citrulline concentrations obtained from the results of a newborn screening program. The study group consists of 52 children with isolated cleft lip with or without cleft palate. One hundred and seven healthy children without congenital anomalies serve as controls. Whole blood citrulline levels were measured using tandem mass spectrometry. Two cut-off points of citrulline concentrations were accepted and three groups of participants were analysed: those with (1) low concentrations (8 micromol/L), (2) medium concentrations (8 - 16 micromol/L), and (3) high concentrations (16 micromol/L). Low citrulline levels were significantly more frequent in patients with clefts than in children without congenital anomalies. In the control group, a high level of citrulline was observed nearly two times more often than in affected children (p=0.03). The presented findings, confirming a possible association between newborn citrulline status and the risk of an orofacial cleft, call for further studies in this area and consideration of increased consumption of foods rich in citrulline (or supplements) by women of childbearing age.

A number of genetic studies have been performed to find susceptibility genes for smoking behavior. Recently the polymorphism Mspl in CYP1A1 was reported to facilitate quitting of smoking during pregnancy. We aimed to determine whether polymorphisms of CAT (-330CT), MnSOD2 (c. 47TC), GPX1 (c599CT), the null GSTM1 and GSTT1 are associated with smoking behavior in pregnant women. We found no significant differences in genotypes distribution between women who quit smoking in the first trimester of pregnancy and persistent smokers. Analyzed polymorphisms seems to not influence susceptibility to smoking in the investigated group of women.

Evidence suggests an association between orofacial clefts and maternal smoking, common cold, and stressful life events. 247 mothers of children with an orofacial cleft completed a self-administered survey with questions concerning obstetric history. Of these, 29.6% were smokers in pre-conceptional period. 6.3%, 5.2% and 25.2% of participants reported working exposure to solvents, stressful life events, and common cold in the early pregnancy, respectively. Differences were seen between smokers and non-smokers for preconceptional folic acid supplementation (5.6% vs. 19.9%), multivitamin use (2.8% vs. 6.4%), pre-conceptional health care utilization (15.3% vs. 30.4%), and late enrollment for prenatal care (12 weeks of gestation; 6.2% vs. 1.9%). Improved lifestyles of women of childbearing age is required.

Benign acute childhood myositis (BACM) is characterised by sudden calf pain and inability to walk. We analyzed the characteristics of seven boys and two girls with BACM treated in the Pediatric Department from April 2005 to March 2009. The mean age at onset of symptoms was 7 +/- 2 years. Two boys were hospitalized twice for BACM. All cases occurred in winter or spring. 7 out of all admissions were clustered together in one week long periods. Patients demonstrated prodromal symptoms of flu-like illness followed by the sudden onset of difficulty in walking. One girl additionally complained of a painful right hip. Four patients received inosine pranobex for prodromal viral infection before the clinical onset of myositis. In all cases, creatine phosphokinase (CPK; the highest value at 8988 U/l) and aspartate aminotransferase (AST; the highest value at 329 U/l) values were elevated. The serum concentration of myoglobin was elevated in five out of six tested patients (the highest value at 2172 microg/l). The following haematological abnormalities were detected: leucocytopenia (the lowest WBC 1.35 x 10(3)/microl), neutropenia, and trombocytopenia. All patients made a rapid recovery within 1 to 5 days. Pediatricians and emergency medicine specialists must be aware that BACM is a self-limiting disorder with the acute onset of inability to walk, elevated CPK and AST levels, and transient haematological abnormalities. There is no sufficient data from clinical reports on immunostimulant use before the onset of BACM.

We investigated the relation between concentrations of maternal zinc and copper and the risk of an infant being born with an orofacial cleft. We did a case-control study using 116 mothers of children with isolated cleft lip with or without cleft palate (cleft group), and 64 mothers of unaffected children (control group). Mothers with a whole blood zinc concentration of 47.1 micromol/L or less had a risk 2.5 times higher of having a child with an orofacial cleft than those with a higher concentration (or level) (95% CI 1.03-6.23; p

Humans are highly adapted to consuming probiotics. Trehalose ("mushroom" sugar) is probably an important reserve compound and stress-responsible metabolite (increases bile and gastric acid resistance) of probiotic bacteria's and trehalase activity, in contrast to lactase activity, is preserved in all human populations, even those not consuming mushrooms. Among traditional Melanesian horticulturists, of whom 4/5 are daily smokers, the diet is rich in pre- and probiotics and there is absence of cancer and cardiovascular disease. Indoor air pollution is an important cancer risk factor. Over thousands of years, the controlled use of fire for preparing meals has resulted in exposure to smoke pollution (biomass fuels produce up to 100 times more respirable particles compared to gas ovens). Simultaneously, up until the 20th century, the only commonly available and inexpensive way of preserving food was fermentation and drying. Probiotics may protect the detoxification function of the kidney and liver. Furthermore, it can be speculated that probiotics may help in adaptation to smoke pollution generated during cooking, heating but also tobacco smoking. Smoking is the most important lifestyle risk factor for bladder cancer and the consumption of probiotic foods reduces the risk of this cancer in humans. Probiotics may restore natural killer cell activity which is lowered in smokers. In one study it was observed that a diet supplemented with Lactobacillus plantarum could be also useful in the prevention of cardiovascular disease in smokers. There is no sufficient data from clinical trials to recommend the routine use of probiotics in prevention of smoking-related diseases. More research is needed to investigate the role of probiotics in this area.

In the 19-th and early 20-th centuries the regions of the Green Forest and White Forest (Central Poland) comprised a reservoir of rural people living on the verge of biological existence. Despite material deficiencies, tobacco smoking addiction was common--nearly 100% of the male population was smokers. An analysis of ethnographic findings suggests that the permanence of addiction could have been caused by 1. the early initiation of smoking and acceptance of smoking by under-ages, 2. the spreading of the practice of replacing tobacco, when in deficit, by other materials such as dried potato leaves, clover leaves or even feces of horses. One can assume that stimuli linked with non-tobacco-exposed smoking may also have an important influence on maintaining addiction.

Celiac disease is known to predispose patients to disturbances in bone metabolism. However, little information is available on the biochemical bone turnover markers in celiac children treated with gluten-free diet.The aim of presented study was to assess bone resorption and formation processes by biochemical bone turnover markers in children with celiac disease on gluten-free diet.We studied 20 children with celiac disease (age range 1.5 - 16 yr; 11 girls, 9 boys). The mean age of diagnosis was 2.6 +/- 1.9 yr and the mean duration of gluten-free diet was 7.8 +/-5.1 yr. Results were compared with those obtained in 130 healthy children. Serum levels of bone-specific alkaline phosphatase and osteocalcin as bone formation indices and serum level of C-telopeptide of type I collagen as bone resorption index were measured by immunoenzymatic methods. Additionally, serum vitamin D, calcium and phosphorus were also estimated.Lower median values of C-telopeptide of type I collagen were observed in about 50% tested celiac patients. Some of them also had lower osteocalcin level. However, in most patients ranges of values of bone turnover markers were similar to those in the controls. During our observation, all tested children had normal serum concentration of vitamin D as well as of calcium and phosphorus.Our data show normal bone resorption and formation processes in most patients with celiac disease on gluten-free diet. However, some cases had changes in the pattern of bone turnover markers. Further studies of these patients are needed to assess their predisposition to osteopenia and osteoporosis.