Exploring the Importance of Differential Expression of Autophagy Markers in Term Placentas from Late-Onset Preeclamptic Pregnancies.

Preeclampsia (PE) is a serious hypertensive disorder affecting 4-5% of pregnancies globally, leading to maternal and perinatal morbidity and mortality and reducing life expectancy in surviving women post-gestation. Late-onset PE (LO-PE) is a clinical type of PE diagnosed after 34 weeks of gestation, being less severe than the early-onset PE (EO-PE) variant, although both entities have a notable impact on the placenta. Despite the fact that most studies have focused on EO-PE, LO-PE does not deserve less attention since its prevalence is much higher and little is known about the role of the placenta in this pathology. Via RT-qPCR and immunohistochemistry methods, we measured the gene and protein expressions of several macroautophagy markers in the chorionic villi of placentas from women who underwent LO-PE (n = 68) and compared them to normal pregnancies (n = 43). We observed a markedly distinct expression pattern, noticing a significant drop in NUP62 expression and a considerable rise in the gene and protein expressions of ULK1, ATG9A, LC3, ATG5, STX-17, and LAMP-1 in the placentas of women with LO-PE. A major induction of autophagic processes was found in the placental tissue of patients with LO-PE. Abnormal signaling expression of these molecular patterns in this condition aids in the understanding of the complexity of pathophysiology and proposes biomarkers for the clinical management of these patients.

Exacerbated Activation of the NLRP3 Inflammasome in the Placentas from Women Who Developed Chronic Venous Disease during Pregnancy.

Chronic venous disease (CVD) comprises a spectrum of morphofunctional disorders affecting the venous system, affecting approximately 1 in 3 women during gestation. Emerging evidence highlights diverse maternofetal implications stemming from CVD, particularly impacting the placenta. While systemic inflammation has been associated with pregnancy-related CVD, preliminary findings suggest a potential link between this condition and exacerbated inflammation in the placental tissue. Inflammasomes are major orchestrators of immune responses and inflammation in different organs and systems. Notwithstanding the relevance of inflammasomes, specifically the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3)- which has been demonstrated in the placentas of women with different obstetric complications, the precise involvement of this component in the placentas of women with CVD remains to be explored. This study employs immunohistochemistry and real-time PCR (RT-qPCR) to examine the gene and protein expression of key components in both canonical and non-canonical pathways of the NLRP3 inflammasome (NLRP3, ASC-apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain-caspase 1, caspase 5, caspase 8, and interleukin 1ß) within the placental tissue of women affected by CVD. Our findings reveal a substantial upregulation of these components in CVD-affected placentas, indicating a potential pathophysiological role of the NLRP3 inflammasome in the development of this condition. Subsequent investigations should focus on assessing translational interventions addressing this dysregulation in affected patient populations.

Increased Expression of Tetraspanins, ALIX and HSP-70 in the Placenta Tissue of Women with Chronic Venous Disease during Pregnancy.

Chronic venous disease (CVD) is a complex and common vascular disorder characterized by increased blood pressure and morpho-functional changes in the venous system like varicose veins. Pregnancy is one of the main risk factors for suffering from this condition. Despite the consequences of CVD during pregnancy remains to be fully understood, compelling evidence support that this condition represents an important stress for the mother and the fetus, leading to significant histopathological changes in the placenta. Tetraspanins (CD9, CD63, and CD81), ALG-2-interacting protein X (Alix), and heat-shock protein (HSP-70) are cellular components involved in multiple biological processes under homeostatic and disease conditions. Despite some studies that have evidence of their relevance in the placenta tissue and pathological pregnancies, there is limited knowledge regarding their role in pregnancy-associated CVD. In this sense, the present work aims to analyze gene and protein expression of these components in the placenta of women with CVD (n=62) in comparison to healthy women (n=52) through RT-qPCR and immunohistochemistry, respectively. Our results show an increased gene and protein expression of the different studied markers, suggesting their potential involvement in the pathological environment of the placenta of women who undergo CVD during pregnancy. In this sense, further studies should be directed to deep into the potential implications of these changes to understand the effects and consequences of this condition in maternofetal wellbeing.

Clinical and Translational Applications of Serological and Histopathological Biomarkers in Metastatic Breast Cancer: A Comprehensive Review.

Breast cancer is one of the most common malignancies worldwide and the most common form of cancer in women. A large proportion of patients begin with localized disease and undergo treatment with curative intent, while another large proportion of patients debuts with disseminated metastatic disease. In the last subgroup of patients, the prognosis in recent years has changed radically, given the existence of different targeted therapies thanks to the discovery of different biomarkers. Serological, histological, and genetic biomarkers have demonstrated their usefulness in the initial diagnosis, in the follow-up to detect relapses, to guide targeted treatment, and to stratify the prognosis of the most aggressive tumors in those with breast cancer. Molecular markers are currently the basis for the diagnosis of metastatic disease, given the wide variety of chemotherapy regions and existing therapies. These markers have been a real revolution in the therapeutic arsenal for breast cancer, and their diagnostic validity allows the classification of tumors with higher rates of relapse, aggressiveness, and mortality. In this sense, the existence of therapies targeting different molecular alterations causes a series of changes in tumor biology that can be assessed throughout the course of the disease to provide information on the underlying pathophysiology of metastatic disease, which allows us to broaden our knowledge of the different mechanisms of tissue invasion. Therefore, the aim of the present article is to review the clinical, diagnostic, predictive, prognostic utility and limitations of the main biomarkers available and under development in metastatic breast cancer.

Assessment of Tissue Expression of the Oxytocin-Vasopressin Pathway in the Placenta of Women with a First-Episode Psychosis during Pregnancy.

Psychosis refers to a mental health condition characterized by a loss of touch with reality, comprising delusions, hallucinations, disorganized thought, disorganized behavior, catatonia, and negative symptoms. A first-episode psychosis (FEP) is a rare condition that can trigger adverse outcomes both for the mother and newborn. Previously, we demonstrated the existence of histopathological changes in the placenta of pregnant women who suffer an FEP in pregnancy. Altered levels of oxytocin (OXT) and vasopressin (AVP) have been detected in patients who manifested an FEP, whereas abnormal placental expression of these hormones and their receptors (OXTR and AVPR1A) has been proven in different obstetric complications. However, the precise role and expression of these components in the placenta of women after an FEP have not been studied yet. Thus, the purpose of the present study was to analyze the gene and protein expression, using RT-qPCR and immunohistochemistry (IHC), of OXT, OXTR, AVP, and AVPR1a in the placental tissue of pregnant women after an FEP in comparison to pregnant women without any health complication (HC-PW). Our results showed increased gene and protein expression of OXT, AVP, OXTR, and AVPR1A in the placental tissue of pregnant women who suffer an FEP. Therefore, our study suggests that an FEP during pregnancy may be associated with an abnormal paracrine/endocrine activity of the placenta, which can negatively affect the maternofetal wellbeing. Nevertheless, additional research is required to validate our findings and ascertain any potential implications of the observed alterations.

Overexpression of glycolysis markers in placental tissue of pregnant women with chronic venous disease: a histological study.

Chronic Venous Disease (CVD) refers to a wide variety of venous disorders being the varicose veins its most common manifestation. It is well-established the link between pregnancy and the risk of suffering CVD, due to hormonal or haematological factors, especially during the third trimester. In the same manner, previous studies have demonstrated the detrimental effect of this condition in the placental tissue of pregnant women, including in the normal physiology and the metabolomic profile of this organ. In this context, the aim of this study was to evaluate the glucose homeostasis in the placental tissue of women presenting CVD. Through immunohistochemistry, we studied the protein expression of the glucose transporter 1 (GLUT-1), Phosphoglycerate kinase 1 (PGK1), aldolase (ALD), Glyceraldehyde-3-phosphate dehydrogenase (GA3PDH) and lactate dehydrogenase (LDH). Our results have reported a significative increase in the expression of GLUT-1, PGK1, ALD, GA3PDH and the isoenzyme LDHA in placentas of women with CVD. This work has proven for the first-time an altered glucose metabolism in the placental tissue of women affected by CVD, what may aid to understand the pathophysiological mechanisms of this condition in more distant organs such as placenta. Furthermore, our research also supports the basis for further studies in the metabolic phenotyping of the human placenta due to CVD, which may be considered during the late pregnancy in these women.

Chronic Venous Disease during Pregnancy Causes a Systematic Increase in Maternal and Fetal Proinflammatory Markers.

Chronic venous disease (CVD) is a common vascular disorder characterized by increased venous hypertension and insufficient venous return from the lower limbs. Pregnancy is a high-risk situation for developing CVD. Approximately a third of the women will develop this condition during pregnancy, and similarly to arterial hypertensive disorders, previous evidence has described a plethora of alterations in placental structure and function in women with pregnancy-induced CVD. It is widely known that arterial-induced placenta dysfunction is accompanied by an important immune system alteration along with increased inflammatory markers, which may provide detrimental consequences for the women and their offspring. However, to our knowledge, there are still no data collected regarding cytokine profiling in women with pregnancy-induced CVD. Thus, the aim of the present work was to examine cytokine signatures in the serum of pregnant women (PW) with CVD and their newborns (NB). This study was conducted through a multiplex technique in 62 PW with pregnancy-induced CVD in comparison to 52 PW without CVD (HC) as well as their NB. Our results show significant alterations in a broad spectrum of inflammatory cytokines (IL-6, IL-12, TNF-α, IL-10, IL-13, IL-2, IL-7, IFN-γ, IL-4, IL-5, IL-21, IL-23, GM-CSF, chemokines (fractalkine), MIP-3α, and MIP-1ß). Overall, we demonstrate that pregnancy-induced CVD is associated with a proinflammatory environment, therefore highlighting the potentially alarming consequences of this condition for maternal and fetal wellbeing.

Brain-Derived Neurotrophic Factor Levels in Cord Blood from Growth Restricted Fetuses with Doppler Alteration Compared to Adequate for Gestational Age Fetuses.

Background and Objectives: Fetal growth restriction (FGR) is a severe obstetric disease characterized by a low fetal size entailing a set of undesired consequences. For instance, previous studies have noticed a worrisome association between FGR with an abnormal neurodevelopment. However, the precise link between FGR and neurodevelopmental alterations are not yet fully understood yet. Brain-derived neurotrophic factor (BDNF) is a critical neurotrophin strongly implicated in neurodevelopmental and other neurological processes. In addition, serum levels of BDNF appears to be an interesting indicator of pathological pregnancies, being correlated with the neonatal brain levels. Therefore, the aim of this study is to analyze the blood levels of BDNF in the cord blood from fetuses with FGR in comparison to those with weight appropriate for gestational age (AGA). Materials and Methods: In this study, 130 subjects were recruited: 91 in group A (AGA fetuses); 39 in group B (16 FGR fetuses with exclusively middle cerebral artery (MCA) pulsatility index (PI) < 5th percentile and 23 with umbilical artery (UA) PI > 95th percentile). Serum levels of BDNF were determined through ELISA reactions in these groups. Results: Our results show a significant decrease in cord blood levels of BDNF in FGR and more prominently in those with UA PI >95th percentile in comparison to AGA. FGR fetuses with exclusively decreased MCA PI below the 5th percentile also show reduced levels of BDNF than AGA, although this difference was not statistically significant. Conclusions: Overall, our study reports a potential pathophysiological link between reduced levels of BDNF and neurodevelopmental alterations in fetuses with FGR. However, further studies should be conducted in those FGR subjects with MCA PI < 5th percentile in order to understand the possible implications of BDNF in this group.

Patients with Invasive Lobular Carcinoma Show a Significant Increase in IRS-4 Expression Compared to Infiltrative Ductal Carcinoma-A Histopathological Study.

Background and Objectives: Breast cancer (BC) is the first diagnosed type of cancer and the second leading cause of cancer-related mortality in women. In addition, despite the improvement in treatment and survival in these patients, the global prevalence and incidence of this cancer are rising, and its mortality may be different according to the histological subtype. Invasive lobular carcinoma (ILC) is less common but entails a poorer prognosis than infiltrative ductal carcinoma (IDC), exhibiting a different clinical and histopathological profile. Deepening study on the molecular profile of both types of cancer may be of great aid to understand the carcinogenesis and progression of BC. In this sense, the aim of the present study was to explore the histological expression of Insulin receptor substrate 4 (IRS-4), cyclooxygenase 2 (COX-2), Cyclin D1 and retinoblastoma protein 1 (Rb1) in patients with ILC and IDC. Patients and Methods: Thus, breast tissue samples from 45 patients with ILC and from 45 subjects with IDC were analyzed in our study. Results: Interestingly, we observed that IRS-4, COX-2, Rb1 and Cyclin D1 were overexpressed in patients with ILC in comparison to IDC. Conclusions: These results may indicate a differential molecular profile between both types of tumors, which may explain the clinical differences among ILC and IDC. Further studies are warranted in order to shed light onto the molecular and translational implications of these components, also aiding to develop a possible targeted therapy to improve the clinical management of these patients.

Considering the Effects and Maternofoetal Implications of Vascular Disorders and the Umbilical Cord.

The umbilical cord is a critical anatomical structure connecting the placenta with the foetus, fulfilling multiple functions during pregnancy and hence influencing foetal development, programming and survival. Histologically, the umbilical cord is composed of three blood vessels: two arteries and one vein, integrated in a mucous connective tissue (Wharton's jelly) upholstered by a layer of amniotic coating. Vascular alterations in the umbilical cord or damage in this tissue because of other vascular disorders during pregnancy are worryingly related with detrimental maternofoetal consequences. In the present work, we will describe the main vascular alterations presented in the umbilical cord, both in the arteries (Single umbilical artery, hypoplastic umbilical artery or aneurysms in umbilical arteries) and the vein (Vascular thrombosis, aneurysms or varicose veins in the umbilical vein), together with other possible complications (Velamentous insertion, vasa praevia, hypercoiled or hypocoiled cord, angiomyxoma and haematomas). Likewise, the effect of the main obstetric vascular disorders like hypertensive disorders of pregnancy (specially pre-eclampsia) and chronic venous disease on the umbilical cord will also be summarized herein.

Tissue remodelling and increased DNA damage in patients with incompetent valves in chronic venous insufficiency.

Chronic venous insufficiency (CVI), in which blood return to the heart is impaired, is a prevalent condition worldwide. Valve incompetence is a complication of CVI that results in blood reflux, thereby aggravating venous hypertension. While CVI has a complex course and is known to produce alterations in the vein wall, the underlying pathological mechanisms remain unclear. This study examined the presence of DNA damage, pro-inflammatory cytokines and extracellular matrix remodelling in CVI-related valve incompetence. One hundred and ten patients with CVI were reviewed and divided into four groups according to age (<50 and ≥50 years) and a clinical diagnosis of venous reflux indicating venous system valve incompetence (R) (n = 81) or no reflux (NR) (n = 29). In vein specimens (greater saphenous vein) from each group, PARP, IL-17, COL-I, COL-III, MMP-2 and TIMP-2 expression levels were determined by RT-qPCR and immunohistochemistry. The younger patients with valve incompetence showed significantly higher PARP, IL-17, COL-I, COL-III, MMP-2 and reduced TIMP-2 expression levels and a higher COL-I/III ratio. Young CVI patients with venous reflux suffer chronic DNA damage, with consequences at both the local tissue and systemic levels, possibly associated with ageing.

Mouse Models for Human Skin Transplantation: A Systematic Review.

Immunodeficient mouse models with human skin xenografts have been developed in the past decades to study different conditions of the skin. Features such as follow-up period and size of the graft are of different relevance depending on the purpose of an investigation. The aim of this study is to analyze the different mouse models grafted with human skin. A systematic review of the literature was performed in line with the PRISMA statement using MEDLINE/PubMed databases from January 1970 to June 2020. Articles describing human skin grafted onto mice were included. Animal models other than mice, skin substitutes, bioengineered skin, postmortem or fetal skin, and duplicated studies were excluded. The mouse strain, origin of human skin, graft dimensions, follow-up of the skin graft, and goals of the study were analyzed. Ninety-one models were included in the final review. Five different applications were found: physiology of the skin (25 models, mean human skin graft size 1.43 cm2 and follow-up 72.92 days), immunology and graft rejection (17 models, mean human skin graft size 1.34 cm2 and follow-up 86 days), carcinogenesis (9 models, mean human skin graft size 1.98 cm2 and follow-up 253 days), skin diseases (25 models, mean human skin graft size 1.55 cm2 and follow-up 86.48 days), and would healing/scars (15 models, mean human skin graft size 2.54 cm2 and follow-up 129 days). The follow-up period was longer in carcinogenesis models (253 ± 233.73 days), and the skin graft size was bigger in wound healing applications (2.54 ± 3.08 cm2). Depending on the research application, different models are suggested. Careful consideration regarding graft size, follow-up, immunosuppression, and costs should be analyzed and compared before choosing any of these mouse models. To our knowledge, this is the first systematic review of mouse models with human skin transplantation.

Histopathological study of JNK in venous wall of patients with chronic venous insufficiency related to osteogenesis process.

Chronic venous insufficiency (CVI) is one of the most common vascular pathologies worldwide. One of the risk factors for the development of CVI is aging, which is why it is related to senile changes. The main trigger of the changes that occur in the venous walls in CVI is blood flow reflux, which produces increased hydrostatic pressure, leading to valve incompetence. The cellular response is one of the fundamental processes in vascular diseases, causing the activation of cell signalling pathways such as c-Jun N-terminal kinase (JNK). Metabolic changes and calcifications occur in vascular pathology as a result of pathophysiological processes. The aim of this study was to determine the expression of JNK in venous disease and its relationship with the role played by the molecules involved in the osteogenic processes in venous tissue calcification. This was a cross-sectional study that analyzed the greater saphenous vein wall in 110 patients with (R) and without venous reflux (NR), classified according to age. Histopathological techniques were used and protein expression was analysed using immunohistochemistry techniques for JNK and markers of osteogenesis (RUNX2, osteocalcin (OCN), osteopontin (OPN)). Significantly increased JNK, RUNX2, OCN, OPN and pigment epithelium-derived factor (PEDF) protein expression and the presence of osseous metaplasia and amorphous calcification were observed in younger patients (<50 years) with venous reflux. This study shows for the first time the existence of an osteogenesis process related to the expression of JNK in the venous wall.

Abnormal proinflammatory and stressor environmental with increased the regulatory cellular IGF-1/PAPP-A/STC and Wnt-1/ß-Catenin canonical pathway in placenta of women with Chronic venous Disease during Pregnancy.

Lower limbs venous insufficiency refers to a wide variety of venous disorders grouped by the term of chronic venous disease (CVD). Hemodynamic and hormonal changes related to pregnancy period, may promote the development of CVD affecting approximately 1 in 3 women. It has been shown that the presence of this condition is associated with damage and placental suffering. Thus, taking IGF-1/PAPP-A/STC-2, inflammatory cytokines production, PI3K/Akt and Wnt/ ß-catenin pathways as a part of the alterations that occurs in the placenta due to CVD, the aim of this study will be to examine the main components of these pathways. Genic and protein expression of PAPP-A, STC-2, IGF-1, IRS-4 Wnt-1, ß-catenin, c-myc, Cyclin D1, IL-4/IL-6 and PI3K/Akt/mTOR pathway will be analysed through RT-qPCR and immunohistochemical techniques in women with CVD (n=62) and pregnant women without this condition (HC) (n=52). PAPP-A, IGF-1, IL-4, IL-6, IRS-4, PI3K, Akt, mTOR, Wnt-1, ß-catenin, c-myc and Cyclin D1 expression were found to be increased in women with CVD, whereas STC-2 were decreased in this group, compared to non-affected women. Our study has demonstrated that IGF-1/PAPP-A/STC-2 axis, PI3K/Akt and Wnt/ß-catenin pathways, along with c-myc, Cyclin D1 and inflammatory cytokines are altered in placenta women with CVD. These results extent the knowledge that CVD is associated to a placenta damage with abnormal tissue environment and cellular regulation.

A General Overview on the Hyperbaric Oxygen Therapy: Applications, Mechanisms and Translational Opportunities.

Hyperbaric oxygen therapy (HBOT) consists of using of pure oxygen at increased pressure (in general, 2-3 atmospheres) leading to augmented oxygen levels in the blood (Hyperoxemia) and tissue (Hyperoxia). The increased pressure and oxygen bioavailability might be related to a plethora of applications, particularly in hypoxic regions, also exerting antimicrobial, immunomodulatory and angiogenic properties, among others. In this review, we will discuss in detail the physiological relevance of oxygen and the therapeutical basis of HBOT, collecting current indications and underlying mechanisms. Furthermore, potential areas of research will also be examined, including inflammatory and systemic maladies, COVID-19 and cancer. Finally, the adverse effects and contraindications associated with this therapy and future directions of research will be considered. Overall, we encourage further research in this field to extend the possible uses of this procedure. The inclusion of HBOT in future clinical research could be an additional support in the clinical management of multiple pathologies.

Pregnancy-associated venous insufficiency course with placental and systemic oxidative stress.

The development of lower extremity venous insufficiency (VI) during pregnancy has been associated with placental damage. VI is associated with increased oxidative stress in venous wall. We have investigated potential disturbance/dysregulation of the production of reactive oxygen species (ROS) in placenta and its eventual systemic effects through the measurement of malondialdehyde (MDA) plasma levels in women with VI. A total of 62 women with VI and 52 healthy controls (HCs) were studied. Levels of nicotinamide adenine dinucleotide phosphate-oxidase 1 (NOX1), 2 (NOX2), inducible nitric oxide synthase (iNOS), endothelial (eNOS), poly(ADP-ribose) polymerase PARP (PARP) and ERK were measured in placental tissue with immunohistochemistry and RT-qPCR. Plasma and placental levels of MDA were determined by colorimetry at the two study times of 32 weeks of gestation and post-partum. Protein and gene expression levels of NOX1, NOX2, iNOS, PARP and ERK were significantly increased in placentas of VI. eNOS activity was low in both study groups, and there were no significant differences in gene or protein expression levels. Women with VI showed a significant elevation of plasma MDA levels at 32 weeks of gestation, and these levels remained elevated at 32 weeks post-partum. The MDA levels were significantly higher in placentas of women with VI. Placental damage that was found in the women with VI was characterized by overexpression of oxidative stress markers NOX1, NOX2, and iNOS, as well as PARP and ERK. Pregnant women with VI showed systemic increases in oxidative stress markers such as plasma MDA levels. The foetuses of women with VI had a significant decrease in their venous pH as compared to those from HC women. The situation of oxidative stress and cellular damage created in the placenta is in coexpression with the production of a pH acidification.

Lipidomic profiling of chorionic villi in the placentas of women with chronic venous disease.

Background: Chronic venous disease (CVD) is a prevalent lower limb venous pathology that especially affects women, who also show an increased risk of this disease during pregnancy. Studies have shown significant structural changes in the placentas of women with CVD and several markers of tissue damage have been also described. Patients and Methods: To try to understand the different placental pathologies, research efforts have focused on examining metabolomic profiles as indicators of the repercussions of these vascular disorders. This study examines changes produced in the metabolomic profiles of chorionic villi in the placentas of women with CVD. In a study population of 12 pregnant women, 6 with and 6 without CVD, we compared through mass spectroscopy coupled to ultra-high performance liquid chromatography (UHPLC-MS), 240 metabolites in chorionic villus samples. Results: This study is the first to detect in the placental villi of pregnant women with CVD, modifications in lysophosphatidylcholines and amino acids along with diminished levels of other lipids such as triglycerides, sphingomyelins, and non-esterified omega 9 fatty acids, suggesting a role of these abnormalities in the pathogenesis of CVD. Conclusions: Our findings are a starting point for future studies designed to examine the impacts of CVD on maternal and fetal well-being.

Bone impaction grafting with trabecular metal augments in large defects in young patients: unravelling a new perspective in surgical technique.

BACKGROUND: Acetabular reconstruction with bone impaction grafting in large defects has yielded conflicting results. METHODS: This was a retrospective study of a case series of five patients with a young age (≤50 years) at the time of surgery who had large acetabular defects reconstructed by bone impaction grafting and trabecular metal augments. The mean follow-up was 79 months. We describe the surgical technique in detail. RESULTS: Improvement was significant on the WOMAC and SF-36 scales (p < 0.05). The radiographs taken at the last follow-up examination showed no migration of the polyethylene cup (p = 0.31) or differences in the abduction angle (p = 0.27) compared to the radiographs from the immediate postoperative period. One patient presented two dislocation episodes as a complication. CONCLUSION: The combination of trabecular metal augments with the bone impaction grafting technique in young patients with large acetabular defects provides satisfactory results in the long term and restores the bone stock.

Increased Angiogenesis and Lymphangiogenesis in the Placental Villi of Women with Chronic Venous Disease during Pregnancy.

Pregnancy is a period in a woman's life associated with an increased risk of developing lower extremity chronic venous disease (CVD). Pregnancy-associated CVD is associated with changes in placental villi. We investigated angiogenesis and lymphangiogenesis in the placental villi of women with CVD during pregnancy compared with healthy controls with no history of CVD (HC). An observational, analytical, and prospective cohort study was conducted on 114 women in their third trimester of pregnancy (32 weeks). Sixty-two participants were clinically diagnosed with CVD. In parallel, 52 controls with no history of CVD (HC) were studied. Gene and protein expression of CD31, podoplanin (D2-40), Flt-1, and placental growth factor (PIGF) was analysed by real-time polymerase chain reaction (RT-qPCR) and immunohistochemistry. CD31 and D2-40 gene expression was significantly greater in the placental villi of women with CVD, as were the numbers of vessels positive for CD31 and D2-40. Significantly higher gene and protein expression of Flt-1 and PIGF was observed in the placental villi of women with CVD. Histological analysis showed more placental villi with periodic acid of Schiff (PAS)-positive material in women with CVD. Our results show a connection between pregnancy-associated CVD and leading to higher proangiogenic and lymphangiogenic activity in placental villi.

Local Growth Hormone Therapy for Pressure Ulcer Healing on a Human Skin Mouse Model.

The growth hormone is involved in skin homeostasis and wound healing. We hypothesize whether it is possible to improve pressure ulcer (PU) healing by locally applying the recombinant human growth hormone (rhGH) in a human skin mouse model. Non-obese diabetic/severe combined immunodeficient mice (n = 10) were engrafted with a full-thickness human skin graft. After 60 days with stable grafts, human skin underwent three cycles of ischemia-reperfusion with a compression device to create a PU. Mice were classified into two groups: rhGH treatment group (n = 5) and control group (n = 5). In the rhGH group for local intradermal injections, each had 0.15 mg (0.5IU) applied to the PU edges, once per week for four weeks. Evaluation of the wound healing was conducted with photographic and visual assessments, and histological analysis was performed after complete wound healing. The results showed a healing rate twice as fast in the rhGH group compared to the control group (1.25 ± 0.33 mm2/day versus 0.61 ± 0.27 mm2/day; p-value < 0.05), with a faster healing rate during the first 30 days. The rhGH group showed thicker skin (1953 ± 457 µm versus 1060 ± 208 µm; p-value < 0.05) in the repaired area, with a significant decrease in collagen type I/III ratio at wound closure (62 days, range 60-70). Local administration of the rhGH accelerates PU healing in our model. The rhGH may have a clinical use in pressure ulcer treatment.