Melatonin and Glycine Reduce Uterus Ischemia/Reperfusion Injury in a Rat Model of Warm Ischemia.

Ischemia/reperfusion injury (IRI) remains a significant problem to be solved in uterus transplantation (UTx). Melatonin and glycine have been shown to possess direct cytoprotective activities, mainly due to their antioxidative and anti-inflammatory properties. The aim of this study was to investigate the protective effects of melatonin and glycine and their combination on IRI in a rat model of warm ischemia. In this study, Sprague-Dawley rats were assigned to eight groups, including sham and IRI (n = 80). Melatonin and glycine alone or their combination were administered prior to 1 h of uterus ischemia followed by 1 h of reperfusion. Melatonin (50 mg/kg) was administered via gavage 2 h before IRI and glycine in an enriched diet for 5 days prior to intervention. Uterus IRI was estimated by histology, including immunohistochemistry, and biochemical tissue analyses. Histology revealed that uterus IRI was significantly attenuated by pretreatment with melatonin (p = 0.019) and glycine (p = 0.044) alone as well as their combination (p = 0.003). Uterus IRI led to increased myeloperoxidase expression, which was significantly reduced by melatonin (p = 0.004), glycine (p < 0.001) or their combination (p < 0.001). The decline in superoxide dismutase activity was significantly reduced in the melatonin (p = 0.027), glycine (p = 0.038) and combined treatment groups (p = 0.015) when compared to the IRI control group. In conclusion, melatonin, glycine and their combination significantly reduced oxidative stress-induced cell damage after IRI in a small animal warm ischemia model, and, therefore, clinical studies are required to evaluate the protective effects of these well-characterized substances in uterus IRI.

The Role of Metabolomics in Current Concepts of Organ Preservation.

In solid organ transplantation (Tx), both survival rates and quality of life have improved dramatically over the last few decades. Each year, the number of people on the wait list continues to increase, widening the gap between organ supply and demand. Therefore, the use of extended criteria donor grafts is growing, despite higher susceptibility to ischemia-reperfusion injury (IRI) and consecutive inferior Tx outcomes. Thus, tools to characterize organ quality prior to Tx are crucial components for Tx success. Innovative techniques of metabolic profiling revealed key pathways and mechanisms involved in IRI occurring during organ preservation. Although large-scale trials are needed, metabolomics appears to be a promising tool to characterize potential biomarkers, for the assessment of graft quality before Tx and evaluate graft-related outcomes. In this comprehensive review, we summarize the currently available literature on the use of metabolomics in solid organ Tx, with a special focus on metabolic profiling during graft preservation to assess organ quality prior to Tx.

Custodiol-N Is Superior to Custodiol® Solution in Experimental Rat Uterus Preservation.

Uterus transplantation (UTx) is the first and only available treatment for women with absolute uterine factor infertility. However, clinical application is limited by the lack of organs, ischemia/reperfusion injury, as well as immunosuppression after UTx. Several different preservation solutions are used in experimental and clinical UTx, including Custodiol® solution. Recently, the novel Custodiol-N solution was developed with superior results in organ preservation. However, the solution was not tested yet in UTx. Therefore, the aims of this study were to evaluate the effect of Custodiol-N in uterus prolonged cold preservation time (8 and 24 h), compared to Custodiol® solution. Uterus tissue samples were obtained from adult Sprague Dawley rats (n = 10/group). Cold ischemic injury was estimated by histology, including immunohistochemistry, and biochemical tissue analyses. After 8 h of cold ischemia, higher percentage of tissue edema, necrosis signs and myeloperoxidase expression, as well as lower superoxide dismutase activity were found in Custodiol® compared to Custodiol-N (p < 0.05). These differences were more pronounced after 24 h of cold preservation time (p < 0.05). This study demonstrated that Custodiol-N protects uterus grafts from cold ischemic injury better than standard Custodiol® most likely via inhibition of oxidative stress and tissue edema. It seems that iron chelators in the composition of Custodiol-N play an important protective role against cold ischemia.

Reasons for Breastfeeding Cessation in the First Year after Childbirth in Lithuania: A Prospective Cohort Study.

Objectives: to identify the main reasons of breastfeeding cessation in Lithuania and if there is a link between the length of maternity leave and breastfeeding cessation. Methods: a prospective questionnaire study was conducted in a tertiary hospital from 2016 to 2017. The sample size included 449 women. Results: a total of 41% (n = 123) of respondents weaned off by 6 months after birth, and 57.8% (n = 173) between 6 months and 1 year. During the first few days after delivery, mothers did not breastfeed their infants mainly due to shortage of milk (n = 10; 40%) or separation from their baby due to infant health problems (n = 12; 48%) (p < 0.0001). Mothers who did not breastfeed during the first days after birth more often did not start breastfeeding later at home (p = 0.001). Going back to work was not a significant factor in weaning off. Conclusions: breastfeeding initiation and practice during the first few days after birth has a significant impact on the further commitment for full breastfeeding. Additionally, a perceived lack of support and help from both doctors and midwives influences a woman's decision to choose not to breastfeed.

Predictors of exclusive breastfeeding in the first six months: four consecutive surveys in a tertiary hospital in Lithuania.

BACKGROUND: There are little up-to-date data available on the duration of exclusive breastfeeding in Lithuania. The aim of our study was to examine the factors that could influence exclusive breastfeeding during the first 6 months of life. METHODS: In 2016, a survey was conducted at the Obstetrics and Gynecology Clinic of Vilnius University Hospital, Santaros Klinikos. Women in postnatal wards were opportunistically offered questionnaires and later followed up by telephone interviews at 6 weeks, 3 months, and 6 months postpartum. We used binary logistic regression to determine the factors that impacted exclusive breastfeeding during the first 6 months following childbirth. RESULTS: Of 475 eligible women that were approached, a total of 447 women were recruited, with response rates of 76.1, 71.4 and 67.0% at 6 weeks, 3 months, and 6 months postpartum, respectively. The prevalence of exclusive breastfeeding through the 6 month postpartum period was 39.8%. Exclusive breastfeeding during days 2 to 4 postpartum was positively influenced by factors such as a natural childbirth, the practice of breastfeeding on demand and maternal self-confidence in breastfeeding. Subsequently, exclusive breastfeeding on demand in the immediate postpartum period and exclusive breastfeeding for up to 3 months were associated with successful exclusive breastfeeding up to 6 months. However, the adverse factors that limited the success and duration of exclusive breastfeeding included free samples of human milk substitutes or advertising at primary healthcare centers 6 weeks after childbirth, pacifier use 6 months after childbirth, as well as amniotomy for labor induction. CONCLUSIONS: Our research demonstrated that exclusive breastfeeding is impacted in both directions by a range of factors during particular periods after delivery. One of the novel findings was the adverse influence of amniotomy for labor induction on exclusive breastfeeding rates. Taking into account diverse factors influencing exclusive breastfeeding and the absence of a single way to promote it, there is a crucial need to increase the incidence of exclusive breastfeeding until infants reach the age of 6 months.

Dietary Melatonin and Glycine Decrease Tumor Growth through Antiangiogenic Activity in Experimental Colorectal Liver Metastasis.

Despite multimodal treatment strategies, clinical outcomes of advanced stage colorectal cancer (CRC) patients remain poor. Neoadjuvant/adjuvant chemotherapy efficacy is limited due to chemoresistance, toxicity, and negative side effects. Since both melatonin and glycine have anti-cancer activities without relevant side effects, this study was designed to investigate their combined effects in experimental CRC liver metastases. CRC metastasis with CC531 cells were induced in male Wistar rats. Melatonin and glycine alone or their combination were supplemented for 14 days (n = 100). Blood parameters, a micro-computed tomography scan (tumor volume over time), and immunohistochemistry for Ki67 and CD31 expression in tumor tissue were compared between groups. Melatonin and glycine alone significantly reduced the tumor volume by 63.2% (p = 0.002) and 43% (p = 0.044) over time, respectively, while tumor volume increased by 8.7% in the controls. Moreover, treatment with melatonin and glycine alone reduced the tumor proliferation index. Most interestingly, the combination therapy did not have any influence on the above-mentioned tumor parameters. The leukocyte count was significantly increased with melatonin at the end of the experiment (p = 0.012) which was due to a high lymphocytes count. Tumor microvascular density was significantly reduced in all treatment groups. The results of this study suggest an inhibitory function for melatonin and glycine alone in the case of CRC liver metastasis growth by acting as natural antiangiogenic molecules, followed by angiogenesis-dependent cancer proliferation and immunomodulation.

The role of melatonin in colorectal cancer treatment: a comprehensive review.

Colorectal cancer (CRC) is one of the most common types of cancer worldwide, known as the second leading cause of cancer-related deaths annually. Currently, multimodal treatment strategies, including surgical resection, combined with chemotherapy and radiotherapy, have been used as conventional treatments in patients with CRC. However, clinical outcome of advanced stage disease remains relatively discouraging, due mainly to appearance of CRC chemoresistance, toxicity, and other detrimental side effects. New strategies to overcome these limitations are essential. During the last decades, melatonin (MLT) has been shown to be a potent antiproliferative, anti-metastatic agent with cytotoxic effects on different types of human malignancies, including CRC. Hence, this comprehensive review compiles the available experimental and clinical data analyzing the effects of MLT treatment in CRC patients and its underlying molecular mechanisms.

Ischemia and reperfusion injury in uterus transplantation: A comprehensive review.

Uterus transplantation (UTx) is the only available treatment for human beings who cannot carry children out to term. However, despite several clinical studies with a very limited number of UTx many issues have to be addressed. Up to date, there is a limited number of successful UTx with livebirth and the majority was achieved with live donors. Wide clinical application is inherently limited by the lack of organs, ischemia/reperfusion injury (IRI) as well as immunosuppression after UTx. The objective of this comprehensive literature review is to discuss these arising limitations of UTx with main focus on strategies to reduce IRI. This review showed, that usage of immunosuppressants, opioids or supplements, like amino acids, protects uterus from IRI, improving rising level of antioxidants and decreasing level of oxidative stress markers. The available data of experimental and clinical studies was compiled and will be discussed.

A Rare Case Report of Thoracic Ectopia Cordis: An Obstetrician's Point of View in Multidisciplinary Approach.

Ectopia cordis is a rare congenital anomaly associated with the heart positioned outside of the thoracic cavity either partially or completely. It can be associated with other congenital abnormalities. Overall, the prognosis for infants with ectopia cordis is very poor but depends greatly on the type and severity of ectopia cordis and intracardiac and associated malformations. We present one case of a fetus with prenatally diagnosed thoracic ectopia cordis with intracardiac defects and omphalocele, all the abnormalities seen in pentalogy of Cantrell except a diaphragmatic defect. Considering poor prognosis for fetus, conservative management of prenatal care has been chosen. At the 42nd gestational week, during the active stage of labor, due to fetal distress, cesarean section was performed at a tertiary level hospital. The condition of the infant was impairing rapidly and the newborn succumbed within 24 hours. We discuss the perinatal care concerning this rare anomaly.