Evaluation of the Regulatory Role of Circadian Rhythm Related Long Non-Coding RNAs in ADHD Etiogenesis.

OBJECTIVE: ADHD is associated with increased sleep problems and circadian rhythm disturbances. This study aimed to examine ADHD patients and healthy controls in terms of chronotypic features and expression levels of CLOCK, PER1, lncRNA HULC, lncRNA UCA1. METHOD: Eighty-three children were included (43 ADHD). Conner's Parent Rating Scale-Revised Short Form, Childhood Chronotype Questionnaire, Children's Sleep Disorders Scale were administered. Gene expression levels were studied from peripheral blood. RESULTS: Evening chronotype, sleep initiation/maintenance disorder, sleep-wake transition disorder, excessive sleepiness disorder were higher in the ADHD group compared to the controls in the scales reported by the parents. Expression levels of all examined genes were statistically significantly higher in the ADHD group. There was no significant relationship between genes and sleep parameters in the ADHD group. CONCLUSION: Our study provides the first evidence that lncRNA HULC and lncRNA UCA1 might have a role in the etiology of ADHD.

The predictive value of vitamin D follow-up and supplementation on recurrence in patients with colorectal cancer.

Aim: Vitamin D has a role in carcinogenesis and may have effect on recurrence. Thus, we aim to analyze the prognostic effect of vitamin D levels at beginning and follow-up together with the contribution of vitamin D supplementation on patients with colorectal cancer (CRC). Materials & methods: CRC patients who underwent curative surgery were included. Patients' vitamin D values were assessed under four groups according to baseline and follow-up vitamin D values, and whether vitamin D supplementation was used. Survival distributions were compared for vitamin D groups. Results: Patients with a high follow-up vitamin D level and a high vitamin D level after supplementation presented with better disease-free survival and overall survival than patients with low vitamin D and low vitamin D levels after supplementation. Conclusion: Follow-up vitamin D values seems to be a good predictive biomarker and vitamin D supplementation may have a positive effect on survival.

Role of prolidase activity and oxidative stress biomarkers in unexplained infertility.

OBJECTIVE: Our aim was to explore the significance of serum prolidase enzyme activity and oxidative stress in women with unexplained infertility (UEI). METHODS: In this case-control study (n = 160; 86 cases; 74 controls) prolidase enzyme activity and total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and vitamin E were measured in plasma using enzyme-linked immunosorbent assays. RESULTS: Prolidase enzyme activity and TAS levels were particularly higher in the patient group (P = 0.013, P = 0.001, respectively). Decreased OSI levels were detected in the patient group (P = 0.001). There was a positive relationship of prolidase with vitamin E in both patient and control groups (r = 0.892, P = 0.001, and r = 0.659, P = 0.001, respectively). A positive, but weak, relationship was identified between prolidase activity and TOS levels and also between vitamin E and TOS levels in the UEI group (r = 0.265, P = 0.049, and r = 0.288, P = 0.014, respectively). No association was found between prolidase and TOS levels or between vitamin E and TOS levels in the control group (r = 0.0097, P = 0.527, and r = 0.085, P = 0.610, respectively). CONCLUSION: Our results showed an association between serum prolidase activity and oxidative stress in UEI patients. Further studies including greater groups are required to show the role of reactive oxygen species in UEI.

Association of the CC chemokine receptor 5 (CCR5) polymorphisms with preeclampsia in Turkish women.

AIM: Endothelial dysfunction and inflammation are involved in the pathogenesis of preeclampsia. The CC chemokine receptor 5 (CCR5) modulates inflammation secondary to endothelial dysfunction and related vascular disorders, by initiating chemotaxis. In this study, we examined the frequency of two polymorphisms, the CCR5D32 deletion and the CCR5-59029 A/G promoter point mutation in women with preeclampsia. METHODS: The CCR5 polymorphisms were genotyped in 74 preeclamptic and 128 controls who had been unaffected by preeclampsia in previous pregnancies. Genotyping was performed with the polymerase chain reaction and restriction fragment length polymorphism. Statistical evaluations were made using the chi-square test or Fisher's exact test when appropriate. RESULTS: The percentage of wild-type allele bearers (?/?plus ?/D32 genotypes) in the preeclamptic group was significantly higher than that of non-bearers (98.6 vs.91.4%, P = 0.03, by the Fisher's exact test). The number of the individuals with D32/D32 genotype was significantly high in the control group (P = 0.035). D32 allele revealed a 2.3-fold protective effect against the risk of preeclampsia.When the percentage of G allele bearers of CCR5 59029A/G polymorphism was compared between the groups, a significant increase was seen in preeclamptics (P = 0.002). CONCLUSION: CCR5 polymorphisms significantly influenced the susceptibility to preeclampsia in our study population consisted of Caucasians. The role of chemokines in this syndrome appears to be an important issue.

-765 G→C and -1195 A→G promoter variants of the cyclooxygenase-2 gene decrease the risk for preeclampsia.

Cyclooxygenase-2 (COX-2) is the inducible isoenzyme of COX that leads to increased production of prostaglandins and thromboxane, the mediators of inflammation. Controversial data regarding COX levels or activities in the placentas of women with preeclampsia have led us to examine whether a single nucleotide polymorphism (SNP) in the COX-2 gene is associated with the onset of preeclampsia. Two polymorphisms in the promoter region of COX-2 gene were examined by the polymerase chain reaction and restriction fragment length polymorphism in 128 controls and 74 preeclamptic patients. Genotype distribution and allelic frequencies for -765G→C polymorphism of COX-2 gene were significantly different between patients and controls (p=0.000 and p=0.042, respectively). The odds ratio (OR) for preeclampsia risk associated to the -765G allelic variant was 4.07 (95% confidence interval [CI]: 0.89-18.56). The AA genotype of the -1195 A→G variant was present at a significantly higher frequency among all preeclamptic subjects (p=0.000 χ(2): 13.4, OR: 3.44, 95% CI: 1.74-6.77). A moderate linkage was observed between the -765G and -1195A variants (D(0): 0.201; r(2): 0.003). These findings suggest that SNPs, -765G→C and -1195 A→G, on the promoter region of COX-2 gene may reduce the risk of preeclampsia, possibly by affecting the rate of gene expression.

Association of monocyte chemotactic protein-1 and CC chemokine receptor 2 gene variants with preeclampsia.

Preeclampsia complicates 10% of pregnancies in developing countries. It is one of the leading causes of maternal and fetal/neonatal mortality and morbidity worldwide. It has been suggested that maladaptation of the maternal immune response during pregnancy might be a causal factor for preeclampsia. According to immune maladaptation hypothesis, preeclampsia is due to an inappropriate regulation of normally Th2-deviated maternal immune responses, leading to a shift toward harmful Th1 immunity. Several studies indicate that monocyte chemotactic protein-1 (MCP-1) and CC chemokine receptor 2 (CCR2) are involved in Th1 and Th2 immunity. In this study, we investigated the association between MCP-1 A-2518G and CCR2-V64I polymorphisms and preeclampsia. One hundred eighty preeclamptic pregnant women and 145 healthy controls were included in the study. We observed that in preeclamptic women, MCP-1 G: CCR2 Val haplotype was significantly higher when compared with other haplotypes. In conclusion, we stated that MCP-1 and CCR2 gene variants might be associated with preeclampsia.

Serum total antioxidant status and lipid peroxidation marker malondialdehyde levels in overt and subclinical hypothyroidism.

BACKGROUND: Mitochondria are the main production site of free oxygen radicals, which can cause organ dysfunction by oxidation of cellular macromolecules such as carbohydrates, lipids and proteins. Oxidative stress may result from either overproduction of these species or from failure of the antioxidant defence systems. Thyroid hormones have well-known effects on mitochondrial oxygen consumption, but data about how hypothyroidism affects oxidative stress are controversial, and little is known about oxidative stress in subclinical hypothyroidism. Total antioxidant status (TAS) gives information about all of the antioxidants in the organism, while malondialdehyde (MDA) is a lipid peroxidation marker used to assess lipid peroxidation due to increased oxidative stress. We aimed to determine how hypothyroidism and subclinical hypothyroidism affect serum MDA and TAS. SUBJECTS AND METHODS: Serum TAS, MDA, C-reactive protein levels and lipid compositions were studied in 20 hypothyroid, 40 subclinical hypothyroid and 40 healthy subjects. RESULTS: MDA was elevated in both hypothyroid and subclinical hypothyroid patients compared with controls, while TAS levels show no significant differences between groups. Low-density lipoprotein (LDL) cholesterol levels were significantly high in both hypothyroid and subclinical hypothyroid patients. Triglyceride levels were high only in hypothyroid patients when compared with the controls. MDA showed a correlation with LDL cholesterol, total cholesterol and triglyceride. CONCLUSIONS: These results suggest an increased oxidative stress in both hypothyroid and subclinical hypothyroidism states, which can be explained by both the insufficient increase in the antioxidant status and the altered lipid metabolism in these cases.

Association of pre-eclampsia with hyperhomocysteinaemia and methylenetetrahydrofolate reductase gene C677T polymorphism in a Turkish population.

BACKGROUND: Hyperhomocysteinaemia is a common finding in a wide variety of pathological conditions that exhibit endothelial disturbances. In the pathogenesis of pre-eclampsia, endothelial cell activation or dysfunction has been proposed as a central feature, and the presence of hyperhomocysteinaemia in varying degrees has been detected. One of the known causes of hyperhomocysteinaemia is polymorphism in the methylenetetrahydrofolate reductase gene that lowers the activity of the enzyme. AIMS: In the current study, we measured plasma homocysteine concentrations in pre-eclamptic pregnants, and searched for the altered methylenetetrahydrofolate reductase (MTHFR) gene in which the cytosine 677 was replaced by the thymine (C677T polymorphism). METHODS: The study groups consisted of 64 pre-eclamptic and 47 normotensive healthy pregnant women in their third trimester. The C677T transition in the MTHFR gene was detected by HinfI restriction enzyme analysis and subsequent electrophoresis in a 3% agarose gel. Total homocysteine concentrations were measured by high performance liquid chromatography. RESULTS: The prevalence of the homozygous mutant thymine-thymine genotype was non-significant in the pre-eclamptic group. Total homocysteine in the plasma of pre-eclamptic women was found to be increased in comparison with healthy pregnant women (P < 0.001). Any influence of the allelic distribution on plasma homocysteine concentrations was not detected in either group. However, pre-eclamptic patients bearing the non-mutated cytosine-cytosine genotype had significantly higher homocysteine levels than those with an uncomplicated pregnancy (P = 0.009), ruling out the possibility that the presence of a mutated allele is associated with the hyperhomocysteinaemia seen in pre-eclamptic women. CONCLUSION: In our pre-eclamptic study population, a mild hyperhomocysteinaemia was observed. This finding seems to be a consequence of hypertension and vascular injury rather than an independent factor with a genetic origin.

Effects of hyperbaric oxygen therapy on caustic esophageal injury in rats.

BACKGROUND/PURPOSE: Caustic esophageal burn is a serious problem in pediatric surgery. Even though many clinical and experimental studies had been performed, the complication rate could not be reduced to a satisfying level. In this study, the authors evaluated the effects of hyperbaric oxygen (HBO) therapy in caustic esophageal burn in rats. METHODS: Rats were divided into 4 groups, and caustic burn at the distal esophagus was created by applying 50% NaOH for 3 minutes in all groups. The first and third groups did not receive HBO therapy. HBO therapy was applied to the second group for 2 days and to the fourth group for 28 days. To evaluate the effects of short-term HBO therapy, the first 2 groups were compared for ulceration, inflammation, and submucosal vascular thrombosis after 2 days. The third and fourth groups were compared for the long-term effects of HBO therapy. Rats in these groups were killed after 28 days and compared for the collagen content, weight, and mortality rate. RESULTS: In the second group, which received 2 days of HBO therapy, ulcer depth and vascular thrombosis were significantly lower than these in the first group (P =.022 and P =.020, respectively). The fourth group, which received 4 weeks of HBO therapy, had a significantly reduced mortality rate, weight loss, and collagen score and hydroxyproline level if compared with the third group (P =.035; P =.016; P =.028; and P =.033, respectively). CONCLUSIONS: These results indicate that HBO therapy is useful in caustic esophageal burn both in short-term and long-term use.

The association between preeclampsia and angiotensin-converting enzyme insertion/deletion polymorphism.

BACKGROUND: Plasma and tissue angiotensin-converting enzyme (ACE) activities are believed to be under genetic control. Increased ACE activity due to the deletion polymorphism of the ACE gene is associated with a wide variety of diseases that exhibit endothelial disturbances. Available reports suggest that the incidence of ACE gene deletion polymorphism associated with preeclampsia varies depending on the study population and geographic location. In this study, we examined the insertion/deletion genotype distribution and the activity of ACE in preeclamptic pregnants. METHODS: Ninety-five preeclamptic and 50 normotensive pregnant patients, both in their third trimester, as well as 39 healthy nonpregnant individuals were included in the study. Gene polymorphism was studied by the polymerase chain reaction followed by the agarose electrophoresis. Pearson's chi(2) test was used for the statistical evaluation of the allele frequency, and Student's t-test for the ACE activity. RESULTS: The presence of D allele was found to be associated with preeclampsia (p<0.05, odds ratio=1.53; df=1; 95% CI=1.007-2.338). The influence of allelic distribution on the enzyme activity was observed in the preeclamptics bearing II genotype, who exhibited significantly lower activity of ACE than that of the patients with the other genotypes (p<0.05). CONCLUSION: We found an association between the genotype II and low ACE activity in preeclamptic women and an association between D allele frequency and preeclampsia. Pregnancy alone did not have an effect on the ACE activity.