Third trimester intrauterine fetal death: proposal for the assessment of the chronology of umbilical cord and placental thrombosis.

The timing of umbilical cord and placental thrombosis in the third trimester intrauterine fetal death (TT-IUFD) may be fundamental for medico-legal purposes, when it undergoes medical litigation due to the absence of risk factors. Authors apply to human TT-IUFD cases a protocol, which includes histochemistry and immunohistochemistry (IHC) for the assessment of thrombi's chronology. A total of 35 thrombi of umbilical cord and/or placenta were assessed: 2 in umbilical artery, 6 in umbilical vein, 15 in insertion, 10 in chorionic vessels, 1 in fetal renal vein, 1 in fetal brachiocephalic vein. Thrombi's features were evaluated with hematoxylin-eosin, Picro-Mallory, Von Kossa, Perls, and immunohistochemistry for CD15, CD68, CD31, CD61, and Smooth Muscle Actin. The estimation of the age of the thrombi was established by applying neutrophils/macrophages ratio taking into consideration, according to literature, the presence of hemosiderophagi, calcium deposition, and angiogenesis. To estimate an approximate age of fresh thrombi (< 1 day), a non-linear regression model was tested. Results were compared to maternal risk factors, fetal time of death estimated at autopsy, mechanism, and cause of death. Our study confirms that the maternal risk factors for fetal intrauterine death and the pathologies of the cord, followed by those of the placental parenchyma, are the conditions that are most frequently associated with the presence of thrombi. Results obtained with histological stainings document that the neutrophile/macrophage ratio is a useful tool for determining placental thrombi's age. Age estimation of thrombi on the first day is very challenging; therefore, the study presented suggests the N/M ratio as a parameter to be used, together with others, i.e., hemosiderophagi, calcium deposition, and angiogenesis, for thrombi's age determination, and hypothesizes that its usefulness regards particularly the first days when all other parameters are negative.

Human umbilical cord perivascular cells prevent chemotherapeutic drug-induced male infertility in a mouse model.

OBJECTIVE: To study whether intratesticular (IT) administration of 2 sources of human umbilical cord perivascular cells (HUCPVC), rich and potent sources of mesenchymal stromal cells (MSC), before chemotherapy can prevent infertility in a mouse model. DESIGN: Two control groups of CD1 male mice without busulfan (BUS) administration (untreated and IT media injection groups) were included. Experimental groups included IT administration of media, first trimester (FTM) HUCPVCs or term HUCPVCs (n = 5 each) injected 3 days before BUS treatment (20 mg/kg). All groups were included in a mating time course study over 6 months. SETTING: Preclinical study in a fertility center research laboratory. PATIENTS: Not applicable. INTERVENTION: IT delivery of FTM or term HUCPVC before BUS treatment. MAIN OUTCOME MEASURES: Pregnancies, litter sizes, and gross morphology of offspring were monitored. Caudal epididymal sperm concentration, motility, and progressive motility were assessed by computer-assisted sperm analysis. Spermatogenesis was also assessed histologically in testicular tissue sections. RESULTS: FTM and term HUCPVC displayed an MSC-associated immunophenotype and expressed transcripts encoding paracrine factors known to regulate the testicular cell niche. IT administration of FTM and term HUCPVC before chemotherapy promoted the recovery of spermatogenesis and fertility compared with BUS-treated animals that received a media injection. Although the total number of pups sired over 6 months by males treated with FTM or term HUCPVC was reduced compared with untreated or media-injected controls, litter size and sperm parameters in fertile animals did not differ between control and cell-treated groups. CONCLUSION: HUCPVC represent a promising source of MSC-based therapy to prevent gonadotoxic chemotherapeutic drug-induced infertility.

The risk of hyperbilirubinemia in term neonates after placental transfusion - a randomized-blinded controlled trial.

OBJECTIVE: We aimed to demonstrate non-inferiority of delayed cord clamping (DCC) and cord milking (CM) in comparison to early cord clamping (ECC) in the incidence of hyperbilirubinemia requiring phototherapy. MATERIAL AND METHODS: 467 of maternal-foetal dyads were screened for eligibility. 389 term infants, of breastfeeding, non-smoking mothers were randomized to receive ECC ( < 40 s), DCC (1-2 min) or CM (4 times towards the neonate). The primary outcome was defined as hyperbilirubinemia requiring phototherapy. RESULTS: 307 patients were included in the analysis. CM did not increase the risk of phototherapy RR 11.27 95% CI (0.80; 2.04). Similar results were achieved when comparing DCC and ECC, RR 1.29 95% CI (0.82; 2.05). This was also true for CM vs DCC, RR 0.99 95% CI (0.64; 1.52). The prevalence of total serum bilirubin (TSB) at 24-48 hours was 10.8 mg/dL; 10.33 mg/dL and 11.39 in ECC, CM and DCC group respectively. Transcutaneous bilirubin (TcB) levels at 24-48 h were 7.58 mg/dL, 7.89 mg/dL and 7.60 mg/dL in the ECC, CM and DCC respectively. None of the neonates met exchange transfusion criteria or symptomatic polycythaemia. CONCLUSIONS: Our study suggests that placental transfusion is not associated with hyperbilirubinemia requiring phototherapy or exchange transfusion.

Canine umbilical cord perivascular tissue: A source of stem cells for therapy and research.

There are numerous sources of multipotent mesenchymal stromal cells (MSC) with therapeutic potential, and bone marrow is the main one. However, pain, lack of donors and comorbidities associated with harvesting stimulate the search for new sources of MSCs. The aim of this work is to obtain cells from umbilical cord (UC) perivascular tissue of dogs and characterize them as MSCs. For this, the UC was obtained from therapeutic cesarean sections and submitted to enzymatic digestion. The obtained cells were subjected to growth and proliferation tests, as well as the analysis of surface markers, differentiation test in three mesenchymal lineages and analysis of differentiation markers expression. From all the UC used in this study an adherent with fibroblastoid shape cell was obtained, with an initial number of 4.8 × 105 of cells. The growth curves showed a lag phase from 0 to 24 h, followed by a phase of growth of 24 to 168 h, and then phase of cell decay. The doubling time was kept around 15 h until the sixth passage, from which there were signs of cellular senescence. The differentiation assays demonstrated the ability of cells to differentiate into osteoblasts, adipocytes and chondrocytes when subjected to the induction mediums. The study of surface markers was positive for adhesion markers and negative for hematopoietic markers. Thus, cells obtained from canine UC perivascular tissue by enzymatic digestion are multipotent MSC and the protocol developed ensures the perivascular origin of these cells.

Electrical field stimulation induces endothelium-dependent contraction of human umbilical cord vessels.

Electrical field stimulation (EFS) has been used for decades in classical pharmacological preparations in order to characterize the mediators released by neural endings involved in smooth muscle contraction or relaxation. Since most of the human umbilical cord has no innervation, EFS has never been used in this preparation. This study aimed to investigate the effect of EFS on vascular responsiveness from human umbilical cord. Segments of the human umbilical cord were obtained from normotensive parturients and the human umbilical artery (HUA) and the human umbilical vein (HUV) were isolated and mounted in organ bath chambers. Electrical field stimulation-induced contractions in both HUA (2.35 ±â€¯1.31 mN and 3.77 ±â€¯2.31 mN for 8 Hz and 16 Hz respectively, n = 24) and HUV (3.81 ±â€¯2.54 mN and 6.26 ±â€¯4.51 mN for 8 Hz and 16 Hz respectively, n = 25). The addition of tetrodotoxin (1 µM) did not alter the EFS-induced contractions in both tissues (n = 5). Pre-incubation with atropine (10 and 100 µM), glibenclamide (10 µM) and indomethacin (10 µM) did not affect the EFS-induced contractions in both tissues. The contractions of both vessels were significantly reduced by pre-incubation of the tissues with phentolamine (10 and 100 µM). The endothelium removal almost abolished the EFS- induced contractions in both vessels (n = 5). In sandwich preparation, donor tissue (with endothelium) released a factor (s) that promoted contraction of the recipient tissue (endothelium removal) in both HUA and HUV (n = 5, respectively). Our findings indicate a potential role of endothelium-derived catecholamines in modulating HUA and HUV reactivities.

Hemangioma of the umbilical cord with associated amnionic inclusion cyst: two uncommon entities occurring simultaneously.

Umbilical cord hemangioma is an uncommon benign vascular neoplasm arising from the free segment of the umbilical cord, distinct from placental and fetal insertion, and is thought to originate from endothelial cells of the umbilical vessels. Cystic changes in the umbilical cord rarely occur as a consequence of the damage to the amnionic surface of the cord caused by the presence of the hemangioma. Until now, a total of 8 cases of umbilical cord hemangioma associated with cystic changes in the umbilical cord have been reported in the literature, however, among these cases, only one showed an associated cyst derived from inclusion of the amniotic epithelium, and the remaining seven cases consisted of hemangiomas with associated pseudocyst of the umbilical cord. We herein report a case of umbilical cord hemangioma with an associated amnionic epithelial inclusion cyst. Clinicopathological features and differential diagnostic considerations are also discussed.

Negative correlation between testosterone and TNF-α in umbilical cord serum favors a weakened immune milieu in the human male fetoplacental unit.

Clinical and epidemiological evidence supports that pregnancies carrying a male fetus are more vulnerable to infections and preterm birth, probably due to testosterone immunosuppressive properties. In human placentas, testosterone lowers the expression of CYP27B1, the vitamin D (VD)-activating enzyme, diminishing cathelicidin synthesis, a potent VD-dependent antimicrobial peptide (AMP). VD also stimulates other AMPs, including defensins. To get insights into the increased male vulnerability mechanisms, we investigated the relationship between fetal sex and the immunoendocrine milieu at the fetoplacental unit. For this, umbilical vein serum and placental samples were collected from healthy newborns. In males' serum, testosterone levels were significantly higher and negatively associated with TNF-α, a cytokine that strengthens the immune response. Males showed lower serum TNF-α and increased levels and gene expression of the immunosuppressive cytokine IL-10. Only in female samples there was a positive association (P < 0.05) between AMPs and both TNF-α and CYP27B1 and between 25-hydroxyvitamin D3 and IL-1ß serum levels. Accordingly, VD-metabolites (25-hydroxyvitamin D3, calcitriol) significantly stimulated IL-1ß gene expression in cultured trophoblasts. Interestingly, IL-1ß mRNA correlated positively with defensins (P < 0.05) in males, but not with cathelicidin expression, which was significantly diminished in comparison to females. Our data suggest that high umbilical serum testosterone and IL-10 in males could explain reduced TNF-α levels and lack of association between VD-dependent innate immunity markers and proinflammatory cytokines expression in the fetoplacental unit. Altogether, our observations imply a restricted basal immune milieu in males compared to females, which may help understand the higher male susceptibility to adverse perinatal outcomes.

The in vitro growth of a cord blood-derived cell population enriched for CD34+ cells is influenced by its cell cycle status and treatment with hydroxyurea.

OBJECTIVE: Cell cycle plays a fundamental role in the physiology of hematopoietic stem and progenitor cells. In the present study we used a negative selection system to obtain an immature cell population-enriched for cord blood-derived CD34+ cells-and we determined its proliferation, expansion and differentiation patterns as a function of the cell cycle status. The effects of hydroxyurea (HU) were also assessed. RESULTS: As compared with cells in synthesis (S)/Gap2 (G2)/mitosis (M), cells in quiescent state (G0)/Gap1 (G1) showed a higher proliferation potential in vitro. At culture onset, G0, G1 and S/G2/M cells corresponded with 63%, 33% and 4%, respectively. Treatment with HU before culture resulted in an increase in the proportion of cells in G1 with a concomitant decrease in S/G2/M cells, without affecting the proportion of cells in G0. After 3 days of culture in the presence of recombinant cytokines, the vast majority of the cells (90%) were in G1, and by day 8, G0, G1 and S/G2/M cells corresponded with 18%, 67% and 15%, respectively. HU also induced an increase in colony-forming cell (CFC) frequency, in the proliferation and expansion capacities of cultured cells under myeloid conditions, and favored the development of the erythroid lineage. CONCLUSION: Our results show that the in vitro proliferation, expansion and differentiation potentials of immature hematopoietic cells are determined, at least in part, by their cell cycle status and that the cell cycle modifier HU significantly influences the growth of human hematopoietic cells. These results are of potential relevance for the development of ex vivo expansion protocols.

Preparation and Culturing of Human Primary Vascular Cells.

Cerebral amyloid angiopathy (CAA) results from amyloid accumulation within arteries of the cerebral cortex and leptomeninges. This condition is age-related, especially prevalent in Alzheimer's disease (AD), and the main feature of certain hereditary disorders (i.e., HCHWA-I). The vascular smooth muscle cells (VSMCs) appear to play a vital role in the development of CAA, which makes them well suited as an experimental model to study the disease and screen for possible remedies. We describe two different methods for isolating and culturing human VSMCs: First, using the human umbilical cord as an easy source of robust cells, and secondly, using brain tissue that provides the proper cerebral VSMCs, but is more problematic to work with. The umbilical cord also provides human umbilical vascular endothelial cells (HUVEC), useful primary cells for vascular research. Finally, the maintenance, preservation, and characterization of the isolated vascular cells are described.

Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF.

Mesenchymal stem cells (MSCs) have been used for cell-based therapies in regenerative medicine, with increasing importance in central and peripheral nervous system repair. However, MSCs grafting present disadvantages, such as, a high number of cells required for transplantation and low survival rate when transplanted into the central nervous system (CNS). In line with this, MSCs secretome which present on its composition a wide range of molecules (neurotrophins, cytokines) and microvesicles, can be a solution to surpass these problems. However, the effect of MSCs secretome in axonal elongation is poorly understood. In this study, we demonstrate that application of MSCs secretome to both rat cortical and hippocampal neurons induces an increase in axonal length. In addition, we show that this growth effect is axonal intrinsic with no contribution from the cell body. To further understand which are the molecules required for secretome-induced axonal outgrowth effect, we depleted brain-derived neurotrophic factor (BDNF) from the secretome. Our results show that in the absence of BDNF, secretome-induced axonal elongation effect is lost and that axons present a reduced axonal growth rate. Altogether, our results demonstrate that MSCs secretome is able to promote axonal outgrowth in CNS neurons and this effect is mediated by BDNF.

Effect of Delayed Cord Clamping on Hematocrit, and Thermal and Hemodynamic Stability in Preterm Neonates: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the short term clinical effects of delayed cord clamping in preterm neonates. DESIGN: Randomized controlled trial. SETTING: A tertiary care neonatal unit from October 2013 to September 2014. PARTICIPANTS: 78 mothers with preterm labor between 27 to 316/7 weeks gestation. INTERVENTION: Early cord clamping (10 s), delayed cord clamping (60 s) or delayed cord clamping (60 s) along with intramuscular ergometrine (500 µg) administered to the mother. MAIN OUTCOME MEASURES: Primary: hematocrit at 4 h after birth; Secondary: temperature on admission in neonatal intensive care unit, blood pressure (non-invasive) at 12 h, and urinary output for initial 72 h. RESULTS: Mean (SD) hematocrit at 4 h of birth was 58.9 (2.4)% in delayed cord clamping group, and 58.7 (2.1) % in delayed cord clamping with ergometrine group as compared to 47.6 (1.3) % in early cord clamping group. Mean (SD) temperature on admission in NICU was 35.8 (0.2)ºC, 35.8 (0.3)ºC, and 35.5 (0.3)ºC, respectively in these three groups. The mean (SD) non-invasive blood pressure at 12 h of birth was 45.8 (7.0) mmHg, 45.8 (9.0) mmHg, and 35.5 (8.6) mmHg, respectively in these three groups. Mean (SD) urinary output on day 1 of life was 1.1 (0.2) mL/kg/h, 1.1 (0.2) mL/kg/hr and 0.9 (0.2) ml/kg/h, respectively. CONCLUSION: In preterm neonates delayed cord clamping along with lowering the infant below perineum or incision site and administration of ergometrine to mother has significant benefits in terms of increase in hematocrit, higher temperature on admission, and higher blood pressure and urinary output during perinatal transition.

The injury of fine particulate matter from cooking oil fumes on umbilical cord blood vessels in vitro.

Cooking oil fumes (COFs) derived PM2.5 is the major source of indoor air pollution in Asia. For this, a pregnant rat model within different doses of cooking oil fumes (COFs) derived PM2.5 was established in pregnancy in our research. Our previous studies have showed that exposure to COFs-derived PM2.5 was related to adverse pregnancy outcomes. However, the mechanisms of signaling pathways remain unknown. Therefore, this study aimed to investigate the underlying mechanisms induced by COFs-derived PM2.5 injury on umbilical cord blood vessels (UCs) in vitro. Exposure to COFs-derived PM2.5 resulted in changing the expression of eNOS, ET-1, ETRA, and ETRB. In additions, western blot analysis indicated that the HIF-1α/iNOS/NO signaling pathway and VEGF/VEGFR1/iNOS signaling pathway were involved in UCs injury triggered by COFs-derived PM2.5. In conclusion, our data suggested that exposure to COFs-derived PM2.5 resulted in increasing of oxidative stress and inflammation, as well as dysfunction of UCs.

Wait a minute? An observational cohort study comparing iron stores in healthy Swedish infants at 4 months of age after 10-, 60- and 180-second umbilical cord clamping.

BACKGROUND AND OBJECTIVE: Umbilical cord blood (UCB) is a valuable stem cell source used for transplantation. Immediate umbilical cord (UC) clamping is widely practised, but delayed UC clamping is increasingly advocated to reduce possible infant anaemia. The aim of this study was to investigate an intermediate UC clamping time point and to evaluate iron status at the age of 4 months in infants who had the UC clamped after 60 s and compare the results with immediate and late UC clamping. DESIGN: Prospective observational study with two historical controls. SETTING: A university hospital in Stockholm, Sweden, and a county hospital in Halland, Sweden. METHODS: Iron status was assessed at 4 months in 200 prospectively recruited term infants whose UC was clamped 60 s after birth. The newborn baby was held below the uterine level for the first 30 s before placing the infant on the mother's abdomen for additional 30 s. The results were compared with data from a previously conducted randomised controlled trial including infants subjected to UC clamping at ≤10 s (n=200) or ≥180 s (n=200) after delivery. RESULTS: After adjustment for age differences at the time of follow-up, serum ferritin concentrations were 77, 103 and 114 µg/L in the 10, 60 and 180 s groups, respectively. The adjusted ferritin concentration was significantly higher in the 60 s group compared with the 10 s group (P=0.002), while the difference between the 60 and 180 s groups was not significant (P=0.29). CONCLUSION: In this study of healthy term infants, 60 s UC clamping with 30 s lowering of the baby below the uterine level resulted in higher serum ferritin concentrations at 4 months compared with 10 s UC clamping. The results suggest that delaying the UC clamping for 60 s reduces the risk for iron deficiency. TRIAL REGISTRATION NUMBER: NCT01245296.

Vasomotor effects of hydrogen sulfide in human umbilical vessels.

Hydrogen sulfide (H2S) has recently emerged as a biologically active gas with multiple effects on the cardiovascular system. We aimed to investigate the vasomotor actions of sodium sulfide (Na2S), which forms H2S and HS- in solution, in human umbilical artery (HUA) and vein (HUV) rings. In addition, we examined by immunocytochemistry the expression and localization of cystathionine ß-synthase (CBS), cystathionine lyase (CSE), and 3-mercaptopyruvate sulphurtransferase (MPST), the enzymes responsible for endogenous H2S production. Human umbilical vessels were compared with chicken embryo umbilical vessels. HUA and HUV expressed a robust signal for CSE, CBS, and 3-MPST in both endothelial and smooth muscle cells. However, HUA rings did not respond to Na2S (10-6M-10-3M) either at resting tone or during contraction evoked by serotonin or KCl. Similarly, the extraembryonic part of chicken allantoic artery did not respond to Na2S. In contrast, Na2S induced a concentration-dependent contraction in HUV rings under resting tone and a concentration-dependent relaxation when the H2UV rings were contracted with serotonin (42 ± 5% relaxation) or KCl (12 ± 5% relaxation). Na2S-induced contraction of HUV was impaired following removal of extracellular Ca2+, endothelial denudation, NO synthase inhibition (L-NAME), or soluble guanylate cyclase (sGC) inhibition (ODQ). Na2S-induced relaxation of HUV was impaired by the KATP channel inhibitor glibenclamide. In conclusion, H2S does not have vasomotor effects on HUA but induced contraction (mediated through inactivation of the NO/sGC axis) and relaxation (mediated through KATP channels) in HUV. Our data suggest a role for H2S in the venous side of human umbilical circulation.

Ultrastructure and histomorphometric analysis of human umbilical cord vessels in preeclampsia: a potential role of VEGF, VEGFR-1 and VEGFR-2.

AIM: This study aimed to analyze the ultrastructure and histomorphometric changes of the human umbilical cord vessels of preeclampsia compared to healthy pregnancies and the possible role of vascular endothelial growth factor (VEGF) and its receptors. MATERIALS AND METHODS: Umbilical cord (UC) specimens were collected between August, 2014 and July, 2015. Histomorphometric analysis of UC vessels was performed utilizing an image analysis system. Cellular localization of VEGF, VEGFR-1 (VEGF receptor-1) and VEGFR-2 (VEGF receptor-2) were examined in immunohistochemically-stained sections of UC from 45 pregnancies with preeclampsia (PE) and 40 healthy pregnancies. RESULTS: Compared with healthy pregnancies, UC venous measurements were significantly higher in PE; total venous area (p<0.001), luminal venous area (p<0.001) and luminal venous index (p=0.005). Arterial measurements except for the total arterial area were significantly lower in the PE compared to healthy pregnancies, luminal arterial area (p=0.32) and luminal arterial index (p=0.004). Histological and ultrastructural examination of UC from PE revealed discontinuity of vascular endothelium and disorganized edematous widely spaced smooth muscle cells. We demonstrated a significant increase in tissue expression of VEGF in PE (16.6±0.1) compared to healthy pregnancies (12±0.8) (p=0.001). Also, significant higher VEGFR-1 expression in PE (20.5±2.5) compared to healthy pregnancies (9.5±1.2) (p<0.001) has been observed. However, tissue expression of VEGFR-2 was decreased significantly in PE (10.5±0.7) compared to healthy pregnancies (13.8±1.6) (p=0.043). CONCLUSIONS: Altered tissue expression of VEGF and its receptors in the UC vessels could play a crucial role in disturbing the UC vascular endothelium, smooth muscles and measurements and this may underlie the existence of preeclampsia.

Elective caesarean: does delay in cord clamping for 30†s ensure sufficient iron stores at 4†months of age? A historical cohort control study.

OBJECTIVE: To compare iron stores in infants born after elective caesarean section (CS) and a 30 s delay of umbilical cord clamping with those born vaginally after early (≤10 s) or delayed (≥180 s) cord clamping. DESIGN: Prospective observational study with historical control. SETTING: Swedish county hospital. POPULATION: 64 infants born after elective CS were compared with a historical control of 166 early clamped and 168 delayed clamped after vaginal birth. METHODS: Blood and iron status were measured in blood samples collected at birth, 48-96 hours after birth, 4 and 12 months of age. PRIMARY AND SECONDARY OUTCOME MEASURES: Ferritin at 4 months of age was the primary outcome, second outcome measures were other indicators of iron status, and haemoglobin, at 4 and 12 months of age, as well as respiratory distress at 1 and 6 hours after birth. RESULTS: At 4 months infants born by elective CS had better iron status than those born vaginally subjected to early cord clamping, shown by higher adjusted mean difference of ferritin concentration (39 µg/L (95% CI 10 to 60)) and mean cell volume (1.8 fL (95% CI 0.6 to 3.0)); and lower levels of transferrin receptors (-0.39 mg/L (95% CI -0.69 to -0.08)). No differences were seen between infants born after elective CS and delayed clamped vaginally born infants at 4 months. No differences were found between groups at 12 months of age. CONCLUSIONS: Waiting to clamp the umbilical cord for 30 s after elective CS results in higher iron stores at 4 months of age compared with early cord clamping after vaginal birth, and seems to ensure iron status comparable with those achieved after 180 s delayed cord clamping after vaginal birth.

[Influence of delayed cord clamping on preterm infants with a gestational age of <32 weeks].

OBJECTIVE: To investigate the influence of delayed cord clamping (DCC) on preterm infants with a gestational age of <32 weeks. METHODS: Ninety preterm infants with a gestational age of <32 weeks delivered naturally from January to December, 2015 were enrolled and randomly divided into DCC group (46 infants) and immediate cord clamping (ICC) group (44 infants). The routine blood test results, total amount of red blood cell transfusion, blood gas parameters, mean arterial pressure, bilirubin peak, total time of phototherapy, and incidence rates of necrotizing enterocolitis, late-onset sepsis, intracranial hemorrhage, retinopathy, and bronchopulmonary dysplasia were compared between the two groups. RESULTS: Compared with the ICC group, the DCC group had significantly higher levels of hemoglobin, hematocrit, mean arterial pressure, and standard base excess (P<0.05), as well as a significantly lower percentage of preterm infants who underwent volume expansion and dopamine treatment and a significantly lower amount of red blood cell transfusion (P<0.05). The body temperature, pH value, HCO3(-) concentration, serum bilirubin peak, total time of phototherapy, and incidence rates of late-onset sepsis, retinopathy, grade≥2 intracranial hemorrhage, and grade≥2 neonatal necrotizing enterocolitis showed no significant differences between the two groups (P>0.05). CONCLUSIONS: DCC is a safe clinical intervention and can improve the prognosis of preterm infants with a gestational age of <32 weeks.

Unveiling the Differences of Secretome of Human Bone Marrow Mesenchymal Stem Cells, Adipose Tissue-Derived Stem Cells, and Human Umbilical Cord Perivascular Cells: A Proteomic Analysis.

The use of human mesenchymal stem cells (hMSCs) has emerged as a possible therapeutic strategy for CNS-related conditions. Research in the last decade strongly suggests that MSC-mediated benefits are closely related with their secretome. Studies published in recent years have shown that the secretome of hMSCs isolated from different tissue sources may present significant variation. With this in mind, the present work performed a comparative proteomic-based analysis through mass spectrometry on the secretome of hMSCs derived from bone marrow (BMSCs), adipose tissue (ASCs), and human umbilical cord perivascular cells (HUCPVCs). The results revealed that BMSCs, ASCs, and HUCPVCs differed in their secretion of neurotrophic, neurogenic, axon guidance, axon growth, and neurodifferentiative proteins, as well as proteins with neuroprotective actions against oxidative stress, apoptosis, and excitotoxicity, which have been shown to be involved in several CNS disorder/injury processes. Although important changes were observed within the secretome of the cell populations that were analyzed, all cell populations shared the capability of secreting important neuroregulatory molecules. The difference in their secretion pattern may indicate that their secretome is specific to a condition of the CNS. Nevertheless, the confirmation that the secretome of MSCs isolated from different tissue sources is rich in neuroregulatory molecules represents an important asset not only for the development of future neuroregenerative strategies but also for their use as a therapeutic option for human clinical trials.

Methamphetamine, smoking, and gestational hypertension affect norepinephrine levels in umbilical cord tissues.

BACKGROUND: These studies were undertaken to determine methamphetamine (METH) and smoking effects on umbilical vascular dynamics and pregnancy outcomes. MATERIALS AND METHODS: Umbilical cords (54) were collected prospectively at birth, washed of blood, and stored at -80°C. Cords were thawed and lysates prepared, then catecholamine levels quantified with enzyme-linked immunosorbent assay (ELISA). RESULTS: Catecholamine levels in umbilical cords were not associated with maternal or gestational age, gravidity, parity, neonatal or placental weight. Neither smoking nor METH affected dopamine or epinephrine. However, smoking (two-fold) and METH (four-fold) decreased norepinephrine and together a 60-fold reduction occurred (p = 0.025). Cesarean section and hypertension were both associated with lower norepinephrine levels (p < 0.001) regardless of drug status. In normotensive pregnancies, smoking and METH significantly decreased norepinephrine levels (two-fold and 3.5-fold each, respectively) with a 40-fold decrease for METH/smoking together. DISCUSSION: Depletion of norephinephrine by METH and smoking likely contributes to pregnancy complications, including the higher incidence of respiratory distress and postpartum hemorrhage in cesarean section.