Serum Antioxidant Capacity is Preserved in Peritoneal Dialysis Contrary to Its Robust Depletion After Hemodialysis and Hemodiafiltration Sessions

Renal replacement therapy (RRT) may differentially affect systemic generation of reactive oxygen species and depletion of antioxidant pools of low molecular weight molecules and proteins. This study was designed to assess the magnitude of the impairment of serum total antioxidant capacity (TAC) in relation to different RRT modalities. The study included patients on continuous ambulatory peritoneal dialysis (CAPD, N = 21), hemodialysis (HD, N = 21), hemodiafiltration (HDF, N = 20), and healthy controls (N = 33). TAC was assessed by the ferric reducing ability of plasma (FRAP) and with the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay. In CAPD patients, predialysis FRAP and DPPH were increased: 1.46 mM and 10.5% vs. control 1.19 mM and 7.2%, respectively (P < 0.001 in each). In HD and HDF patients, the FRAP and DPPH were significantly increased before and lowered after the RRT session (P < 0.05) if compared with healthy controls. During an HD session, FRAP was decreased from pre-HD 1.71 ± 0.29 mM to post-HD 0.85 ± 0.20 mM (P = 0.0001). The decrease of FRAP was lower during HDF (P < 0.05 vs. HD), it decreased from pre-HDF 1.41 ± 0.43 mM to post-HDF 0.87 ± 0.23 mM (P = 0.0001 vs. pre-HDF). The HD session decreased DPPH from the pre-HD median 10.3%, interquartile range (IR) 9.3–12.0% to post-HD 2.6% IR 2.3–3.1% (P < 0.0001). The adjustment of either urate or bilirubin up to pre-HD levels did not restore lowered post-HD levels of TAC. TAC remains preserved in CAPD, whereas the robust depletion of TAC, lower after HDF than HD sessions, cannot be attributed solely to the washout of dialyzable compounds.     

Axis inhibition protein 2 (AXIN2) polymorphisms may be a risk factor for selective tooth agenesis

Selective tooth agenesis is the most common developmental abnormality of the human dentition. To date, this abnormality has been associated only with mutations in MSX1 and PAX9 mutations, however it has recently been suggested that mutations of axis inhibition protein 2 (AXIN2) may also contribute to this complex anomaly. The protein product of this gene is a negative regulator of the Wnt-signaling pathway. We searched for AXIN2 variants in a group of patients with tooth agenesis who did not have mutations of MSX1 and PAX9. Using multi-temperature single-stranded conformational polymorphism and sequencing analysis, we identified three novel AXIN2 gene variants: c.956+16A>G, c.1060-17C>T and c.2062C>T. We also observed that individuals carrying the c.956+16G and c.2062T alleles exhibited an increased risk of tooth agenesis. The calculated odds ratio was 2.94 (95% CI 1.104–7.816; p=0.026; p_corr=0.234) and 4.01 (95% CI 1.563–10.301; p=0.002; p_corr=0.018), respectively. Moreover, we found that the c.2062C>T transition may change exon splice enhancer-specific binding sites of the protein splicing regulators SC35 and SF2/ASF. This alternation may negatively affect the splicing process and cellular concentration of AXIN2 protein. Our findings suggest that AXIN2 polymorphic variants may be associated with both hypodontia and oligodontia.     

Social acceptance and facial behavior in children with oral clefts.

OBJECTIVE: To examine and compare social acceptance, social behavior, and facial movements of children with and without oral clefts in an experimental setting. DESIGN: Two groups of children (with and without oral clefts) were videotaped in a structured social interaction with a peer confederate, when listening to emotional stories, and when told to pose specific facial expressions. PARTICIPANTS: Twenty-four children and adolescents ages 7 to 16(1)/(2) years with oral clefts were group matched for gender, grade, and socioeconomic status with 25 noncleft controls. MAIN OUTCOME MEASURES: Specific social and facial behaviors coded from videotapes; Harter Self-Perception Profile, Social Acceptance subscale. RESULTS: Significant between-group differences were obtained. Children in the cleft group more often displayed "Tongue Out," "Eye Contact," "Mimicry," and "Initiates Conversation." For the cleft group, "Gaze Avoidance" was significantly negatively correlated with social acceptance scores. The groups were comparable in their ability to pose and spontaneously express facial emotion. CONCLUSIONS: When comparing children with and without oral clefts in an experimental setting, with a relatively small sample size, behavior analysis identified some significant differences in patterns of social behavior but not in the ability to express facial emotion. Results suggest that many children with oral clefts may have relatively typical social development. However, for those who do have social competence deficits, systematic behavioral observation of atypical social responses may help individualize social skills interventions.     

Contribution of IL12A and IL12B Polymorphisms to the Risk of Cervical Cancer

We studied the contribution of the IL12A 3'UTR G>A (rs568408) and IL12B 3'UTR A>C (rs3212227) polymorphisms to the risk of cervical cancer. These polymorphisms were genotyped in four hundred-five patients with cervical cancer and four hundred fifty unrelated healthy females from the Polish population. Logistic regression analysis adjusting for age, pregnancy, oral contraceptive use, tobacco smoking, and menopausal status revealed that the IL12B 3'UTR A>C polymorphism could be a genetic risk factor for cervical cancer. The adjusted odds ratio (OR) for patients with the A/C genotype vs A/A genotype was 1.557 (95?% CI?=?1.173-2.066, p?=?0.0178) and adjusted OR for the C/C or A/C genotype vs the A/A genotype was 1.635 (95?% CI?=?1.241-2.153, p?=?0.0125). However, logistic regression analysis did not show an association of the IL12A 3'UTR G>A polymorphism with cervical cancer development in the studied Polish population. Our studies confirmed that the IL12B 3'UTR A>C polymorphism may be a genetic risk factor for cervical cancer.     

Effects of acute smoking on brain activity vary with abstinence in smokers performing the N-Back task: a preliminary study

We previously reported that compared with a non-deprivation state, overnight abstinence from cigarette smoking was associated with higher brain activity in the left dorsolateral prefrontal cortex (L-DLPFC) during a low demanding working memory challenge, and little increase beyond this activity level during more taxing working memory conditions. In the present study, we aimed to assess how recent smoking (overnight abstinence vs. smoking ad libitum) influenced the effect of smoking a cigarette on brain activity related to a working memory challenge. Six smokers performed the N-Back working memory task during functional magnetic resonance imaging (fMRI) both before and after smoking a cigarette in each of two test sessions: one following overnight abstinence from smoking ( approximately 13 h) and the other following ad libitum smoking. Task-related activity in L-DLPFC showed a significant interaction between the effects of acute smoking, test session, and task load. After overnight abstinence, post-smoking brain activity in L-DLPFC was lower than before smoking at low task load and higher at high task load; corresponding activity on a day of ad libitum smoking was higher at low load and lower at high task load after smoking during the session. These data suggest that the effect of acute smoking on working memory processing depends on recent prior smoking and task load. In particular, they provide preliminary evidence that functional efficiency of working memory is improved by smoking a cigarette during abstinence, while the effect of a cigarette in a non-deprived state varies with the nature and difficulty of the working memory challenge. This interaction merits further examination in larger studies specifically designed to consider this issue.     

Polymorphic variants of genes related to arginine metabolism and the risk of 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.     

Low incidence of hepatic veno‐occlusive disease in pediatric patients undergoing hematopoietic stem cell transplantation attributed to a combination of intravenous heparin,oral glutamine,and ursodiol at a single transplant institution

Lakshminarayanan S, Sahdev I, Goyal M, Vlachos A, Atlas M, Lipton JM. Low incidence of hepatic veno‐occlusive disease in pediatric patients undergoing hematopoietic stem cell transplantation attributed to a combination of intravenous heparin, oral glutamine, and ursodiol at a single transplant institution.
Pediatr Transplantation 2010: 14:618–621. © 2009 John Wiley & Sons A/S. Abstract: We report the low incidence of hepatic VOD in pediatric patients with various diagnoses including hematologic malignancies and non‐malignant conditions transplanted at our institution. Retrospective review of 188 patients who underwent HSCT and received a combined prophylactic regimen of intravenous heparin, oral glutamine, and ursodiol was undertaken. Analysis of the outcome of VOD revealed only one clinical case with acute myeloid leukemia; the patient developed hepatic VOD 10 days after receiving myeloablative chemotherapy with busulfan and CTX followed by HLA‐matched related peripheral blood stem cell transplantation. The low incidence of hepatic VOD in an otherwise high‐risk pediatric transplant population is an important observation, which may be partly attributed to this prophylactic regimen, and warrants further randomized clinical trials for confirmation.     

Polymorphisms located in the region containing BHMT and BHMT2 genes as maternal protective factors for orofacial clefts

Mostowska A, Hozyasz KK, Biedziak B, Misiak J, Jagodzinski PP. Polymorphisms located in the region containing BHMT and BHMT2 genes 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.