Evaluation of umbilical cord immune cells in pregnancies with autoimmune disorders and/or methylenetetrahydrofolate reductase polymorphisms.

OBJECTIVES: To evaluate umbilical cord immune cells in pregnancies with autoimmune disorders (AID) and/or methylenetetrahydrofolate reductase (MTHFR) polymorphisms. METHODS: Umbilical cords were obtained from seven AID women without MTHFR polymorphisms, eight with AID and MTHFR polymorphisms, nine with MTHFR polymorphisms, and eight with neither. Umbilical cords were assessed immunohistologcally by anti-CD4, anti-CD8, anti-CD14, anti-CD19, anti-CD21, and anti-CD56 antibodies in six umbilical cord zones: 1) arterial wall 2) periarterial zone 3) venous wall 4) perivenous zone 5) intervascular zone, and 6) subamniotic zone. RESULTS: AIDs and MTHFR polymorphisms had an effect on the number and composition of CD4+ cells in the venous wall. The presence of a MTHFR polymorphism may affect the number and morphology of CD4+ cells in the subamniotic zone. CD8+ cell distribution is substantially influenced by the presence of maternal risk factors. The co-existence of AID with MTHFR polymorphism has a prominent effect on the number and morphology of CD14+ cells, especially in the arterial wall. CD19+ cells were only observed in the control group in the venous wall, perivenous zone, and intervascular zone. CD21+ cells were only observed in the arterial wall of the control group and the intervascular zone of the AID group with different morphologic features. The number and morphology of CD56+ cells is prominently affected by the presence of maternal risk factors. CONCLUSIONS: Umbilical cord stem cell and immune cell composition may be affected by the presence of risk factors like MTHFR polymorphisms and/or AID.

Low-dose low-molecular-weight heparin prophylaxis against obstetrical complications in pregnancies with metabolic and immunological disorder-associated placental inflammation.

OBJECTIVE: We investigated the importance of prophylactic administration of low-dose low-molecular-weight heparin (LMWH) in women with risk factors associated with placental inflammation. MATERIALS AND METHODS: This retrospective cohort study included 300 pregnant women with a singleton pregnancy (30 primigravidas and 270 multigravidas) who received prophylactic low-dose LMWH to prevent placental inflammation. Based on maternal risk factors, patients were categorized into 3 groups as follows: Group 1: Patients with metabolic risk factors for placental inflammation (n = 205), Group 2: Patients with immunological risk factors for placental inflammation (n = 42), Group 3: Patients with metabolic and immunological risk factors for placental inflammation (n = 53). Obstetric histories, demographic features, clinical characteristics, and present pregnancy outcomes were compared between groups. Live birth rates, composite adverse obstetric outcomes, and the Beksac obstetric index were compared between present and previous pregnancies in multigravidas. RESULTS: Pregnancy outcomes were significantly better in the present pregnancy than in previous pregnancies. A significant increase was observed in live birth rates (33.4% vs. 69.9%, 27.5% vs. 60.5%, and 30.1% vs. 69.4% in groups 1, 2, and 3, respectively) and in the Beksac obstetric index (0.32 vs. 0.43, 0.33 vs. 0.47, and 0.38 vs. 0.57 in groups 1, 2, and 3 respectively) (p < .001 for all). A significant decrease in composite adverse pregnancy outcome rates was observed during the present pregnancy (23.5% vs. 100%, 28.9% vs. 100%, and 24.5% vs. 100% in groups 1, 2, and 3, respectively) (p < .001 for all). Live birth and composite adverse obstetric outcome rates were 70% and 33.3%, respectively in primigravidas. CONCLUSION: Low-dose low-molecular-weight heparin prophylaxis is useful to prevent metabolic and immunological disorders causing placental inflammation, which is the most likely pathophysiological mechanism contributing to various obstetrical complications.

Photobiomodulation combined with adipose-derived stem cells encapsulated in methacrylated gelatin hydrogels enhances in vivo bone regeneration.

Reconstruction of bone defects is still a significant challenge. The aim of this study was to evaluate the effect of application of photobiomodulation (PBM) to enhance in vivo bone regeneration and osteogenic differentiation potential of adipose-derived stem cells (ADSCs) encapsulated in methacrylated gelatin (GEL-MA) hydrogels. Thirty-six Sprague-Dawley rats were randomly separated into 3 experimental groups (n = 12 each). The groups were control/blank defect (I), GEL-MA hydrogel (II), and ADSC-loaded GEL-MA (GEL-MA+ADSC) hydrogel (III). Biparietal critical sized bone defects (6 mm in size) are created in each animal. Half of the animals from each group (n = 6 each) were randomly selected for PBM application using polychromatic light in the near infrared region, 600-1200 nm. PBM was administered from 10 cm distance cranially in 48 h interval. The calvaria were harvested at the 20th week, and macroscopic, microtomographic, and histologic evaluation were performed for further analysis. Microtomographic evaluation demonstrated the highest result for mineralized matrix formation (MMF) in group III. PBM receiving samples of group III showed mean MMF of 79.93±3.41%, whereas the non-PBM receiving samples revealed mean MMF of 60.62±6.34 % (p=0.002). In terms of histologic evaluation of bone defect repair, the higher scores were obtained in the groups II and III when compared to the control group (2.0 for both PBM receiving and non-receiving specimens; p<0.001). ADSC-loaded microwave-induced GEL-MA hydrogels and periodic application of photobiomodulation with polychromatic light appear to have beneficial effect on bone regeneration and can stimulate ADSCs for osteogenic differentiation.

Photobiomodulation with polychromatic light (600-1200 nm) improves fat graft survival by increasing adipocyte viability, neovascularization, and reducing inflammation in a rat model.

OBJECTIVES: Unpredictability with the final volume and viability of the graft are the major concerns in fat grafting. An experimental study was conducted to increase graft retention using photobiomodulation (PBM) with polychromatic light in near-infrared region (600-1200 nm) by utilizing its stimulatory effects on angiogenesis, neovascularization, adipocyte viability, and anti-inflammatory properties. METHODS: A total of 24 rats were divided into four groups (n = 6) according to the applied polychromatic light protocol to the recipient site (none, before fat transfer, after fat transfer, and combined). In all groups, inguinal fat pad was excised, measured for volume and weight, and transferred to the dorsum of the rat. At the end of the experiment, fat grafts were harvested from the recipient site for volume and weight measurements, histological, and immunohistochemical evaluation. RESULTS: Intergroup comparison revealed that fat graft retention regarding weight and volume, was significantly superior in Group IV (p = 0.049 and p = 0.043, respectively), which polychromatic light was applied both before and after transfer of the graft. Hematoxylin-eosin and Masson's trichrome stained sections showed absence of necrosis, fibrosis, inflammation, cyst formation, and increased vascularization of both inner and outer zones of the grafts in Group IV. Also, immunohistochemical staining scores for perilipin (indicator for adipocyte viability), CD31 and VEGF (indicators for angiogenesis and neovascularization) were significantly higher (p < 0.001). Ki67 scores were significantly lower in this group because of anti-inflammatory environment (p < 0.001). CONCLUSIONS: Application of PBM to the recipient site before and after fat transfer improved outcomes in rats at 56 day after fat grafting by means of volume retention, increased neovascularization and adipocyte viability and reduced necrosis, fibrosis and inflammation.

Impact of Prematurity on the Buccal Epithelial Cells of the Neonates via Wnt/Beta-Catenin Signaling Pathway and Apoptosis.

OBJECTIVE: Understanding the reflections of prematurity is necessary for the management of neonatal complications. We focused on the impact of prematurity and related "maternal risk factors/obstetric complications" on buccal cells of the neonates via evaluation of the Wnt/ß-catenin signaling pathway and apoptosis. STUDY DESIGN: This study consisted of "early preterm neonates (EPN) (≤34th gestational week [gw]) (n = 36)," "late preterm neonates (LPN) (34th- < 37th gw) (n = 46)," and "term neonates (control) (≥37th gw) (n = 56)." Cohort was also subclassified according to the presence of maternal risk factors, obstetric complications, and neonatal complications. Wnt/ß-catenin signaling and caspase-3 activation pathways were studied immunocytochemically. RESULTS: Wnt/ß-catenin signaling positivity was statistically more frequent at buccal smears of the EPN and LPN groups compared with controls (p < 0.001). The cutoff for gestational age at delivery in receiver operating characteristic curve with the best balance of sensitivity (67.4%) and specificity (67.3%) was 35.8th gw for determining the reduction of Wnt/ß-catenin signaling positivity (p < 0.001). The study demonstrated that obstetric complications significantly affected the activity of signaling, while maternal risk factors do not have any effect on Wnt/ß-catenin signaling pathway (p = 0.003 and p = 0.828, respectively). This study also demonstrated a significant relationship between Wnt/ß-catenin signaling pathway and the presence of neonatal complications (p = 0.015). CONCLUSION: Dynamic characteristics of buccal cells are influenced by prematurity and related obstetric and neonatal problems. Buccal smear is a good tool to investigate the impact of prematurity and obstetric problems on perinatal outcome. KEY POINTS: · Neonatal buccal cells are affected by prematurity and related obstetric/neonatal problems.. · 35.8th gw is critical for determining the reduction of Wnt/ß-catenin signaling positivity.. · Obstetric and neonatal complications significantly related to Wnt/ß-catenin signaling activity..

Significance of inhibitory maternal killer-cell immunoglobulin-like receptor (KIR) and fetal KIR ligand genotype combinations in placenta related obstetric complications.

Some maternal killer-cell immunoglobulin-like receptor (KIR) and fetal KIR ligand genotypes are associated with obstetric complications, such as recurrent miscarriage, fetal growth restriction, preeclampsia, and preterm birth. However, how KIR/KIR ligand genotypes affect these placenta-related obstetric complications has not been fully understood. We aimed to demonstrate the association of maternal KIR-fetal KIR ligand genotype combinations with immunological/metabolic risk factor associated placenta-related obstetric complications. This study consisted of three groups of pregnant women: 1) Miscarriage group (n = 30), 2) Complicated Pregnancy (CP) group (n = 30), and 3) Control group (n = 30). The observed maternal genotype frequencies of all inhibitory and activating KIRs were similar in all groups (p > 0.05). However, inhibitory 2DL3 was quite frequent in the miscarriage group (p = 0.052). There was no difference between groups in terms of centromeric and telomeric maternal haplotypes (p > 0.05). The fetal group 1 HLA-C genotype was frequently detected in the miscarriage and CP groups with rates of 83.3 % and 93.3 % respectively, while the observed frequency was 70 % in the control group. The fetal group 2 HLA-C genotype was the same in all groups. The results demonstrated significantly less fetal group 2 HLA-C homozygosity in the CP groups when compared to the control group (p = 0.020). The fetal HLA-Bw4 genotype was detected more frequently in the miscarriage and CP groups (p = 0.028 and p = 0.001, respectively). The inhibitory KIR/KIR ligand genotype combinations of 2DL3-C1 and 3DL1-Bw4 were more frequent in the miscarriage and CP groups (p = 0.045 and p = 0.002, respectively). Enhanced NK cell inhibition may be one of the mechanisms underlying placenta-related obstetric complications.

Impact of preterm birth on the cellular characteristics of neonatal buccal cells.

OBJECTIVE: To demonstrate the impact of preterm birth on the cytological, cytomorphometrical, and nuclear parameters of neonatal buccal smears. METHODS: This study consisted of Early Preterm Neonates (EPN; ≤34th gestational week [gw]; n = 36), Late Preterm Neonates (LPN; 34th to <37th gw; n = 46), and Term Neonates (control; ≥37th gw; n = 56). Cytological evaluation and buccal cytome assay were performed using Papanicolaou and Feulgen methods, respectively. RESULTS: Cytological evaluation demonstrated that smear background was cleaner (P < .05) and there were less macrophages in the control group (P < .001). Cyto-morphometric analysis showed that the measurements of nuclear diameter, nuclear area, and nucleus-to-cytoplasm ratio were higher in the preterm (EPN and LPN) versus the control groups (P = .016, P < .001, and P < .001, respectively). We also demonstrated that staining intensity of the nucleus and cytoplasm were less intense in the EPN and LPN groups (P < .001). There was no statistically significant difference between the EPN and LPN groups for any parameters (P > .05). Buccal cytome assay showed that nuclear buds were more prevalent in term newborns compared to preterm neonates (P < .001). CONCLUSIONS: Morphological and cytological properties of neonatal buccal cells are influenced by preterm birth status, and buccal smears may be used as a tool to detect biological markers of neonatal health problems.

Fetal Cell Microchimerism; Normal and Immunocompromised Gestations in Mice.

Objective: To compare fetal cell microchimerism in normal and immunocompromised gestations. Materials and methods: The study consists of two groups of mature female mice. In the control group and the immunocompromised study group, 5 mg of saline and cyclosporine were injected intraperitoneally, respectively. In the second step, all female mice were mated with "Actine-Luc (+) green fluorescent protein (GFP)" transgenic male mice. Immunohistochemical studies (ALPL-antiluciferase, cytokeratin-antiluciferase, and CD 105-antiluciferase) were carried out on maternal liver, skin, and lung tissues at 6-7th and 14-15th gestational days, and postpartum 3-4th, 12th, and 18-24 months. Results: GFP (+) cells were detected in maternal liver and skin but not in lung tissue. Liver was the most affected tissue. GFP was found to be more intense in the immunocompromised group. Conclusion: Fetal microchimerism was demonstrated in maternal liver and skin and found to be more intensive in the immunocompromised group.

Chorionic villus sampling experience of a reference perinatal medicine center.

AIM: To share the chorionic villus sampling (CVS) experience of a single surgeon in our institution. METHODS: This retrospective study consists of CVS cases performed between 2000 and 2018. A total of 66 types of indications were classified under two main categories, the screening group (SG) and the inherited disease group (IDG). The SG and IDG were compared in terms of clinical characteristics of the patients, Beksaç obstetrics index (BOI), timing of CVS in terms of gestational week, and complications and termination of pregnancy (TOP) rate. RESULTS: CVS was performed at 656 women, 69 and 587 of whom were included in the SG and IDG, respectively. CVS indications of the SG were determined as advanced maternal age, high risk in combined test, fetal anomaly suspicion in ultrasonography, and increased nuchal translucency in 23, 23, 14 and 9 cases, respectively. On the other hand, CVS indications of the IDG were hereditary disorders related to hematological, muscular, and metabolic systems for 233, 179, and 116 cases, respectively. Furthermore, 32 patients had a single-gene disorder and 14 had a neurodegenerative disease. According to the results of CVS, 359 fetuses were found to be normal (54.73%), while 205 (31.25%) and 92 (14.02%) fetuses were found to be disorder-positive or carriers, respectively. Two hundred pregnant women accepted TOP. Eight (1.2%) pregnancies ended with abortion after CVS. Statistically significant differences were observed in BOI and TOP rate between SG and IDG (p: 0.042 and 0.013). CONCLUSION: Hereditary disorders were the most common CVS indications and the acceptance of TOP was significantly higher in this group.

Impaired Placentation and Early Pregnancy Loss in Patients with MTHFR Polymorphisms and Type-1 Diabetes Mellitus.

Objective: To evaluate the impact of type-1 diabetes mellitus (DM) and methylenetetrahydrofolate reductase (MTHFR) polymorphisms on impaired placentation leading to early pregnancy loss. Methods: Miscarriage materials were obtained from eight pregnant women with type-1 DM without MTHFR polymorphism, eight with MTHFR polymorphisms without type-1 DM, and eight controls with neither DM nor MTHFR polymorphisms. Insulin-like growth factor-1 (IGF-1), leukemia inhibitory factor (LIF), and Beclin-1 expression were assessed to evaluate placentation. Results: Cytoplasmic LIF, IGF-1, and Beclin-1 expression were decreased in the superficial and glandular epithelial cells of the decidua in both study groups. LIF expression was increased in interstitial trophoblasts in the MTHFR group. IGF-1 expression was decreased in the decidual cells and interstitial trophoblasts in both study groups, while the decrease in stromal cells was noted only in type-1 DM group. Beclin-1 expression was increased in interstitial and villous trophoblasts in both study groups. Conclusion: The expression of IGF-1, LIF, and Beclin-1 are altered in both the decidua and the trophoblasts in pregnancies of women with type-1 DM and MTHFR polymorphisms, compared to normal pregnancies undergoing (elective) terminations.

Photobiomodulation with polychromatic light increases zone 4 survival of transverse rectus abdominis musculocutaneous flap.

OBJECTIVE: The aim of this study was to evaluate the effect of relatively novel approach of application of polychromatic light waves on flap survival of experimental musculocutaneous flap model and to investigate efficacy of this modality as a delay procedure to increase vascularization of zone 4 of transverse rectus abdominis musculocutaneous (TRAM) flap. METHODS: Twenty-one Wistar rats were randomized and divided into 3 experimental groups (n = 7 each). In group 1 (control group), after being raised, the TRAM flap was sutured back to its bed without any further intervention. In group 2 (delay group), photobiomodulation (PBM) was applied for 7 days as a delay procedure, before elevation of the flap. In group 3 (PBM group), the TRAM flap was elevated, and PBM was administered immediately after the flap was sutured back to its bed for therapeutic purpose. PBM was applied in 48 hours interval from 10 cm. distance to the whole abdominal wall both in groups 2 and 3 for one week. After 7 days of postoperative follow-up, as the demarcation of necrosis of the skin paddle was obvious, skin flap survival was further evaluated by macroscopic, histological and microangiographic analysis. RESULTS: The mean percentage of skin flap necrosis was 56.17 ± 23.68 for group 1, 30.92 ± 17.46 for group 2 and 22.73 ± 12.98 for group 3 PBM receiving groups 2 and 3 revealed less necrosis when compared to control group and this difference was statistically significant. Vascularization in zone 4 of PBM applied groups 2 and 3 was higher compared to group 1 (P = 0.001). Acute inflammation in zone 4 of group 1 was significantly higher compared to groups 2 and 3 (P = 0.025). Similarly, evaluation of zone 1 of the flaps reveled more inflammation and less vascularization among the samples of the control group (P = 0.006 and P = 0.007, respectively). Comparison of PBM receiving two groups did not demonstrate further difference in means of vascularization and inflammation density (P = 0.259). CONCLUSION: Application of PBM in polychromatic fashion enhances skin flap survival in experimental TRAM flap model both on preoperative basis as a delay procedure or as a therapeutic approach. Lasers Surg. 51:538-549, 2019. © 2019 Wiley Periodicals, Inc.

Effects of Systemic and Local Caffeine on Vessel Diameter, Anastomosis Patency, and Intimal Hyperplasia in the Rat.

BACKGROUND: The use of caffeine is not recommended prior to elective microsurgery due to its demonstrated negative effects on vessel anastomosis by the presumed sympathomimetic induction of vasoconstriction. In this study, we aimed to elucidate the systemic and local effects of caffeine on vessel diameter, anastomosis patency, and degree of intimal hyperplasia during the healing process. METHODS: Twenty-five rats were randomly assigned to five groups: (1) negative control, (2) preoperative systemic caffeine, (3) postoperative systemic caffeine, (4) perioperative systemic caffeine, and (5) a local caffeine group. Both the right and left femoral arteries were used. Ten anastomoses were performed per group. The arterial diameter was measured by micrometer, anastomosis patency was assessed surgically and histologically, and the histological examination was conducted 3 weeks postoperatively to determine intimal hyperplasia. RESULTS: The overall patency rate was 96%. Mild vasoconstriction was observed in the systemic caffeine groups (statistically insignificant); however, there were no negative effects on anastomosis patency. Local caffeine irrigation resulted in significant vasodilatation in the local caffeine group (p = 0.001); a similar effect was not observed in the other groups. There was a significant decrease in the intima/media ratio in the local caffeine group (p < 0.01), when compared with the control and systemic caffeine groups. No other intima/media ratio differences were observed among other comparison groups. CONCLUSION: The systemic administration of caffeine, although statistically insignificant, has an observable effect on vasoconstriction. However, it does not appear to have negative effects on anastomosis patency regardless of its application period (pre-, post-, or perioperatively). The local application of caffeine resulted in considerable vasodilatation as opposed to the vasoconstriction effect in the systemic caffeine groups. Decreased intimal hyperplasia at the anastomosis edge, and antifibrotic properties in the surgical field were also observed in this group. Histologically, the local caffeine group demonstrated an additional beneficial effect on anastomosis remodeling.

Differential expression of leukemia inhibitory factor and insulin like growth factor-1 between normal pregnancies, partial hydatidiform moles and complete hydatidiform moles.

INTRODUCTION: Leukemia inhibitory factor (LIF) and insulin like growth factor-1 (IGF-1) are two of the most important growth factors mediating trophoblast actions. We hypothesized that the localization and expression patterns of LIF and IGF-1 in partial and complete hydatidiform moles (HM) compared with normal first trimester placentas may provide an understanding of the proliferative processes in HMs. METHODS: The study population included curettage material of women diagnosed as complete or partial HM as a result of histopathological and immunohistochemical examination (complete HM group, n = 8; partial HM group, n = 8) and women undergoing dilatation&curettage for unwanted pregnancies (control group, n = 8). Expression of LIF and IGF-1 among placental cell groups was evaluated immunohistochemically and given a score depending on immunostaining intensity. RESULTS: In normal chorionic villi strong expression of LIF and IGF-1 was present. Both LIF and IGF-1 expressions were weaker in the chorionic villi of complete HMs. In complete mole decidua there was a significant decrease in glandular and endothelial IGF-1 expression along with a decrease in decidual cell LIF expression compared to normal first trimester decidua. LIF expression in extravillous trophoblasts was stronger in complete molar placentas compared to normal placentas. DISCUSSION: LIF and IGF-1 are important regulators of trophoblast proliferation and invasion. Differential expression of LIF and IGF-1 in molar trophoblasts and chorionic villi might have a role in regulation of trophoblasts in complete moles. Decreased expression of glandular IGF-1 and decidual LIF might be related to the decidual changes during trophoblastic proliferation and invasion of decidua in complete HMs.

Estrogen as a novel agent for induction of adipose-derived mesenchymal stem cells for osteogenic differentiation: in vivo bone tissue-engineering study.

BACKGROUND: This study investigated whether the in vivo osteogenic differentiation potential of adipose-derived mesenchymal stem cells is enhanced by 17ß-estradiol. METHODS: Thirty Sprague-Dawley rats were randomized and divided into five experimental groups. For the surgical procedure, biparietal full-thickness bone defects (7 mm in diameter) were created. A chitosan-hydroxyapatite scaffold was used as the vehicle system for 17ß-estradiol-loaded nanoparticles and adipose-derived mesenchymal stem cells. The first group, the blank defect group, was the control group. The defects were filled with either scaffold, estradiol, and scaffold; scaffold and adipose-derived mesenchymal stem cells; or estradiol, scaffold, and adipose-derived mesenchymal stem cells as experimental groups. The rats were killed at the end of weeks 4 and 12, and their calvariae were harvested for histologic and microtomographic evaluation. RESULTS: Micro-computed tomographic evaluation of estradiol, scaffold, and adipose-derived mesenchymal stem cells revealed the highest median value (82.59 ± 17.17), and the difference was significant compared with the blank defect group (p = 0.004). Histologic samples demonstrated a significant difference between experimental groups for bone defect repair at the end of weeks 4 and 12 (p = 0.003 and p < 0.001). The estradiol, scaffold, and adipose-derived mesenchymal stem cell group had the highest median score (3.00 ± 0.0) at week 12, which was significantly higher than scores for the scaffold and adipose-derived mesenchymal stem cell group and the blank defect group. CONCLUSION: 17ß-Estradiol appears to be a novel and promising agent for future cell-based bone tissue-engineering studies.

Evaluation of apoptotic cell death following transient maternal hypotension in fetal rat brain: temporal pattern within the first 24 h after procedure.

BACKGROUND/AIM: To explore the effects of maternal transient systemic hypotension on apoptotic neuronal death in an intrauterine fetal rat brain during the first 24 h after induction of hypotension. MATERIALS AND METHODS: A total of 40 pregnant Sprague-Dawley rats were subjected to either transient systemic hypotension produced for 30 min by blood withdrawal via femoral artery catheterization (hypotension group) or sham operation (control group) on day 15. Two randomly selected fetuses were taken from each rat at 0, 6, 12, and 24 h after the procedure. Apoptosis was evaluated in sections from the whole fetal brain by TUNEL and caspase-3 staining. RESULTS: TUNEL (+) and caspase (+) cells were detected only on the walls of the ventricles of both groups and more abundantly in the hypotension groups than in the control groups at all time points (P <0.05). The increase in TUNEL (+) and caspase (+) cells was highest at 12 h (P < 0.05) following hypotension compared to the other hypotension groups. CONCLUSION: Maternal transient systemic hypotension caused the hypoxia-ischemia (HI)-induced death of immature neurons by apoptosis, and this is especially prominent at 12 h after the insult. Determination of the susceptibility of a developing brain to HI at a certain time may have potential significance on the timing of neuroprotective measures.

The effects of transient systemic hypotension on renal oxidative status, morphology and plasma nitric oxide levels in pregnant rats.

OBJECTIVE: Transient hypotension attacks, frequently experienced during pregnancy, have detrimental effects on maternal and fetal physiology. Despite the strong autoregulatory mechanisms, kidneys are remarkably sensitive to hypoperfusion. Transient hypotension together with high metabolic demand and increased oxygen requirement during pregnancy may disturb the oxidant status and natural course of nitric oxide (NO) metabolism. Therefore, we investigated in this study the effects of systemic hypotension during pregnancy on kidney oxidant status and morphology and plasma NO levels in an experimental hypotension model in rats. METHODS: Twenty-four rats were allocated into four groups as non-pregnant control (NPC), non-pregnant hypotensive (NPH), pregnant control (PC) and pregnant-hypotensive (PH). Blood pressure was monitored only (NPC, PC) or systemic hypotension by blood withdrawal (NPH, PH) was produced for 30 min following catheterisation on the 15th day of pregnancy or at a corresponding time in the control animals. Animals were sacrificed after 48 h of reperfusion. Malonyldialdehyde (MDA) and reduced glutathione (GSH) levels, superoxide dismutase and catalase activities in the kidneys and plasma NO levels were measured. Tissues were evaluated, histologically. RESULTS: Hypotension and/or pregnancy elevated MDA levels, which was significant in the NPH and PH groups (p < 0.05). GSH levels were lower in all groups compared with the NPC group (p < 0.05). Pregnancy itself increased NO only in the control animals (p < 0.05), not in the hypotensive pregnant rats. Transient hypotension resulted in kidney damage in both hypotension groups, and damage was more prominent in renal cortical regions. The most severe effects were seen in the PH group (p < 0.05). CONCLUSIONS: The findings of this study show that transient hypotension induces a kidney injury in pregnant rats. MDA and GSH in kidneys seem to play a role in the pathophysiology of this injury. However, the roles of antioxidant enzymes and NO and the other underlying mechanisms deserve and necessitate further investigation regarding the long-term health of the mother and fetus.