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ABSTRACT Recent research has shown that genetic variations in the oxytocin receptor (OXTR) may be related to variations in subtypes of obsessive-compulsive disorder (OCD). We aimed to explore the relationship between different subtypes of OCD and the genetic variation between rs1316193 and rs4686301 of the OXTR. In this case-control study, 92 OCD patients and 92 healthy controls were included in the OCD and control groups, respectively. The Y-BOCS scale was used to assess the severity of the OCD symptoms. The fasting peripheral blood samples were collected to extract DNA. rs4686301 and rs13316193 were genotyped using restriction fragment length polymorphism analysis techniques. Whether the gene frequency of the locus and the distribution of allele frequency were related to OCD were further study by TaqMan allele typing. The rs4686301 locus differed significantly between behavior and control groups. The genotype frequency and allele frequency at the rs4686301 locus were statistically significant between behavior and control groups (P<0.05). There was significant difference in the genotype frequency at the rs13316193 locus between behavior and control groups (P<0.05). The rs4686301 polymorphism of the OXTR may affect the clinical subtype of OCD. The rs13316193 polymorphism of the OXTR may be a risk factor for obsessive-compulsive behavior.
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PURPOSE@#Evidence suggests that the oxytocin receptor (OXTR) gene may be involved in the psychopathology of posttraumatic stress disorder (PTSD). This study aimed to investigate the effects of OXTR rs53576 genotype on PTSD symptoms introduced in the Diagnostic and Statistical Manual, Fifth Edition (DSM-5).@*METHODS@#This study was a cross-sectional study conducted among 1140 adults who had personally experienced the Wenchuan earthquake. PTSD symptoms were measured with the PTSD checklist for DSM-5. A custom-by-design 2 × 48-Plex SNPscan@*RESULTS@#The results revealed that the rs53576 genotype could significantly predict PTSD symptoms (β = 0.055, p = 0.045). Further analysis showed that the rs53576 genotype was only significantly associated with dysphoric arousal symptoms of PTSD (β = 0.080, p = 0.005). The rs53576 genotype × earthquake exposure interaction had no significant effect on different symptom clusters (p > 0.05).@*CONCLUSION@#This study showed that the rs53576 genotype was only associated with the dysphoric arousal symptoms but not with other symptom clusters of PTSD. These findings support the role of the OXTR on the psychopathology of PTSD and help us to understand the genetic basis of PTSD.
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Objective To investigate the expression of oxytocin ( OXT ) and oxytocin receptor (OXTR) in the prefrontal cortex of postpartum depression (PPD) rats induced by restraint stress during pregnancy and to observe the antidepressant effect of oxytocin and its analogue capitoxin and its mechanism. Methods Twenty-four adult female SD rats of SPF grade were randomly divided into control group,PPD +saline group,PPD + oxytocin group and PPD + captopril group with 6 rats in each group. Rats were subjec-ted to restraint stress for 2 hours every day on the 8th to 21st day of pregnancy to establish PPD model. While the rats in control group were not given any treatment. Rats in PPD + saline,PPD + oxytocin and PPD +captopril were injected bilaterally into prefrontal cortex (PFC) at 10 days postpartum (1 μl/side),oxytocin (30 ng/side) and captopril (45 ng/side) respectively once a day for 5 days. The depressive behaviors of rats were detected by sugar-water preference experiment. Rats were sacrificed 18 days after delivery. The ex-pression of OXT was detected by ELISA method,OXTR by Western blot,Iba-1 by immunofluorescence,and IL-1β,IL-6 and TNF-α by qRT-PCR. Results (1) The sucrose consumption of the PPD + saline group ((67. 1±10. 4)%) was significantly lower than that of the control group((92. 6± 3. 9)%,t=-5. 31,P<0. 01). (2) The expression of oxytocin in prefrontal cortex in PPD group was significantly lower than that in control group ((0. 03±0. 01) ng/mg) vs (0. 08 +0. 05) ng/mg,t=-2. 67,P<0. 05). However,there was no significant difference in the expression of oxytocin receptor between PPD group and control group ((0. 90 ±0. 06) vs (0. 90±0. 05),t=0. 709,P=0. 517). (3) The sucrose consumption of PPD+saline group de-creased than that of control group((65. 6±16. 9)% vs (91. 5±3. 5)%,t=3. 35,P<0. 001). Compared with PPD+saline group,the sucrose consumption of PPD+oxytocin group ((81. 8±8. 4)%) and PPD+carbetocin group ((78. 4±9. 4)%) increased(t=1. 98,1. 68,both P<0. 05). (4) The expression of Iba-1 in the pre-frontal lobe of PPD + saline group was higher than that of control group ((1. 15±0. 05) vs (1. 04 +0. 06), t=3. 50,P<0. 01). Compared with PPD + saline group,the expression of Iba-1 in PPD + oxytocin group (1. 03±0. 06) and in PPD + captopril group (1. 00±0. 02) were lower (t=-3. 50,-6. 55,both P<0. 01). (5) The expression of inflammatory factors IL-1β mRNA (1. 0±0. 1),IL-6 mRNA (1. 1±0. 1) and TNF-α mRNA (1. 7±0. 4) in the prefrontal cortex of rats in the PPD group were higher than that in the control group (IL-1β mRNA (0. 7± 0. 3),IL-6 mRNA (0. 9± 0. 1),TNF-α mRNA ( 1. 1± 0. 3),t=1. 92,3. 19, 2. 43 respectively,all P<0. 05). The expression of inflammatory factors IL-1β,IL-6 and TNF-α mRNA of the PPD+oxytocin group(IL-1β mRNA (0. 6±0. 1),IL-6 mRNA (0. 9±0. 1),TNF-α mRNA (1. 2±0. 4) )and the PPD+carbetocin group ( IL-1β mRNA ( 0. 7± 0. 1),IL-6 mRNA ( 0. 9 ± 0. 1),TNF-α mRNA ( 1. 0 ± 0. 2))in the prefrontal cortex were lower than that in the PPD group(t=-3. 17,-2. 78,-1. 84,t=-2. 76,-2. 40,-2. 94 respectively,all P<0. 05). Conclusion Oxytocin and capitoxin injected into prefrontal cortex can effectively improve depression-like behaviors in PPD model rats. Activation of microglia and decrease of inflammatory factors in prefrontal cortex may be the potential antidepressant mechanism.
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Aims: To evaluate the efficacy, safety and tolerability of atosiban in delaying preterm labour. Study Design: A prospective, open label, non comparative study. Place of Study: Lokmanya Tilak Municipal Medical College Mumbai, India. Methodology: Pregnant women (N=110) between the gestational age of 24 to 34 weeks, presenting with signs of preterm labour were enrolled in the study. Efficacy, safety and tolerability of Atosiban were assessed for a period of 72 hrs. Results: Ninety Eight patients (89.09%) remained undelivered up to 72 hrs after completion of treatment phase and ninety seven patients (88.18%) till the end of their hospital stay (upto 7 days). There were six patients with twin and one with quadruplet pregnancy; atosiban therapy was successful in delaying labour upto discharge from hospital in all the seven patients. The study medication was well tolerated as no adverse events were observed throughout the study duration. Conclusion: Atosiban, an oxytocin receptor antagonist, has proven to be an effective and well tolerated tocolytic drug and because of its favourable safety profile, it may be the best choice as a tocolytic therapy to delay the preterm labour.
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Oxytocin ( OT ) is a cyclic neuropeptide containing nine amino acids residues, in addition to the traditional roles of uterine contraction and lactation, it also plays important roles in the central nervous system and other peripheral organs, such as improving schizophrenia, autism - related psychiatric and psy-chological symptoms. Oxytocin exhibits its physiological func-tions by binding to its receptor (oxytocin receptor,OTR). Cur- rently researchers are manipulating OT system by developing new OTR ligand ( agonists and antagonists ) , hoping to prevent and treat OTR related diseases. This paper reviews the latest devel-opment of OTR agonists, antagonists and its physiological roles in central nerve system and peripheral organs.
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Objective To investigate the improve effects of environmental enrichment on maternal behavior in the adult female rats thatexperienced early-life stress,and to explore the molecular biological mechanism.Methods The newborn Wistar rats were divided into two groups randomly,the early life stress group and the control group.Pups from the former were separated from their mothers once per day for 4 hours from PND 2-21 (day of birth was considered PND =0),and suffered vicious stimulus during the daily 4 hours maternal separation from PND 8-21.On PND 22(weaning),pups from the early life stress group were divided into two groups:12 female pups were reared singly,refered to as isolated-rearing group; another 12 were placed in a big cage that was filled with all sorts of rodents toys,refered to as enriched-rearing group; control female pups were placed in groups of 4 per cage.Mating with male rats when female pups reached PND66,then being placed in cages singly when they were detected pregnant.Maternal behavior was evaluated on the second and sixth day after delivery,and the hypothalamic OTR mRNA levels were examined by RT-PCR.Results The results of maternal behavior observation showed that the total time of retrieve and the latency of licking were significantly longer in isolated-rearing rats compared with the normal and the enriched-rearing rats (P ＜ 0.01) ; total time of licking in enriched-rearing rats was longer than the normal and the isolated-rearing rats(P＜0.01) on the sixth day after delivery;and the score of the nest building was obviously lower in isolated-rearing rats,especially on the sixth day after delivery(P ＜ 0.01).Hypothalamic OTR mRNA levels in the isolated-rearing rats showed strongly decreased compared with the normal rats(P＜0.01),but which close to normal levels in enriched-rearing rats.Conclusion Early life stress can damage some components of maternal behavior,such as retrieval,licking,nest building,but it has no obvious effect on crouching behavior; it also decreases the hypothalamic OTR mRNA levels of the adult female rats; as a kind of early environmental intervention,groups-rearing could make hypothalamic OTR mRNA levels of the female rats that subjected to early life stress restore to normal,and thus reverse the disruptions of stress in maternal behavior.
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Purpose To investigate the effects of oxytocin(OT) and prostaglandins intervention on oxytocin receptor(OTR) expression of primary culture of human myometrial smooth muscle cell.Methods Using respectively oxytocin, prostaglandin E2(PGE2),and prostaglandin F2alpha(PGF2alpha) intervened on human myometrial smooth muscle cell.The expression of OTR mRNA and protein of cell hemogenate was examined.Results The expression of OTR between oxytocin intervention group and untreated group was similar.The expression of OTR in cell was significantly higher in the PGE2 or PGF2alpha intervention group than that in the untreated group.The expression of OTR in cell was significantly higher in the PGE2 and PGF2alpha joint intervention group than that in the untreated group and than that in the PGE2 or PGF2alpha individual intervention group.Conclusion Oxytocin didn′t increse the expression of OTR in human myometrial smooth muscle cell.PGE2 and PGF2alpha incresed the expression of oxytocin receptor in human myometrial smooth muscle cell.Furthermore PGE2 and PGF2alpha joint intervention more significantly increased the expression of oxytocin receptor than PGE2 or PGF2alpha individual intervention in human myometrial smooth muscle cell.
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Objective To study the differential expressions of labour-associated genes,including interleukin-8 (IL-8),oxytocin receptor (OTR) and prostaglandin H synthase type-2 (PGHS-2)) between preterm labour and term labour myometrium and their clinical significance.Methods Seventeen cases of preterm labour (PTL) and 31 cases of preterm no labour (PTNL) of pregnant women were selected as study group,while 6 cases of term labour (TL) and 6 cases term no labour (TNL) of pregnant women were chosen as control.Lower myometrial tissue biopsies were collected to detect the expressions of IL-8,OTR and PGHS-2 by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) as well as Western blot analysis.The expression data were then statistically analyzed in combination with clinical data.Results In the lower myometrial tissues,the mRNA levels of IL-8 and PGHS-2 were significantly lower in PTL group than in TL samples (P0.05),but the PGHS-2 mRNA level was significantly higher in TL group than in TNL group (P0.05).Correlation analysis suggested that the mRNA level of IL-8 was significantly correlated with gestational age in PTNL group (r=0.294,P=0.042).Multiple linear regression analysis showed a mutual control effect of the expressions of IL-8,OTR and PGHS-2 in preterm but not in term labour group.Conclusion Our results show that there are significant differences of the expression of labour-associated genes in lower myometrum between preterm labour and term labour,which might becorrelated with the progression of preterm labour.
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Atosiban is a representative drug of oxytocin receptor antagonists and has a good effect on preterm's treatment. It inhibits oxytocin's effect competitively by binding to oxytocin receptor on myometrial and decidual. It also prevents the second messager formation and calcium mobilization. The studies up to date have shown that Atosiban effectively inhibits uterine contractions with little side effects. The article briefly summarizes the current understanding of Atosiban.