Nitric oxide releasing nanofiber stimulates revascularization in response to ischemia via cGMP-dependent protein kinase.

Nitric oxide (NO) promotes angiogenesis via various mechanisms; however, the effective transmission of NO in ischemic diseases is unclear. Herein, we tested whether NO-releasing nanofibers modulate therapeutic angiogenesis in an animal hindlimb ischemia model. Male wild-type C57BL/6 mice with surgically-induced hindlimb ischemia were treated with NO-releasing 3-methylaminopropyltrimethoxysilane (MAP3)-derived or control (i.e., non-NO-releasing) nanofibers, by applying them to the wound for 20 min, three times every two days. The amount of NO from the nanofiber into tissues was assessed by NO fluorometric assay. The activity of cGMP-dependent protein kinase (PKG) was determined by western blot analysis. Perfusion ratios were measured 2, 4, and 14 days after inducing ischemia using laser doppler imaging. On day 4, Immunohistochemistry (IHC) with F4/80 and gelatin zymography were performed. IHC with CD31 was performed on day 14. To determine the angiogenic potential of NO-releasing nanofibers, aorta-ring explants were treated with MAP3 or control fiber for 20 min, and the sprout lengths were examined after 6 days. As per either LDPI (Laser doppler perfusion image) ratio or CD31 capillary density measurement, angiogenesis in the ischemic hindlimb was improved in the MAP3 nanofiber group; further, the total nitrate/nitrite concentration in the adduct muscle increased. The number of macrophage infiltrations and matrix metalloproteinase-9 (MMP-9) activity decreased. Vasodilator-stimulated phosphoprotein (VASP), one of the major substrates for PKG, increased phosphorylation in the MAP3 group. MAP3 nanofiber or NO donor SNAP (s-nitroso-n-acetyl penicillamine)-treated aortic explants showed enhanced sprouting in an ex vivo aortic ring assay, which was partially abrogated by KT5823, a potent inhibitor of PKG. These findings suggest that the novel NO-releasing nanofiber, MAP3 activates PKG and promotes therapeutic angiogenesis in response to hindlimb ischemia.

Amputated Digit Replantations: Critical Digit Ischemia Timing, Temperature, and Other Predictors of Survival.

INTRODUCTION: A common consideration for replantation success is the ischemia time following injury and the preservation temperature. A classic principle within the hand surgery community describes 12 hours of warm ischemia and 24 hours of cold ischemia as the upper limits for digit replantation; however, these limits are largely anecdotal and based on older studies. We aimed to compare survival data from the large body of literature to aid surgeons and all those involved in the replantation process in hopes of optimizing success rates. METHODS: The PubMed database was queried on April 4th, 2023, for articles that included data on digit replantation survival in terms of temperature of preservation and ischemia time. All primary outcomes were analyzed with the Mantel-Haenszel method within a random effects model. Secondary outcomes were pooled and analyzed using the chi-square statistic. Statistical analysis and forest plot generation were completed with RevMan 5.4 software with odds ratios calculated within a 95% confidence interval. RESULTS: Our meta-analysis identified that digits preserved in cold ischemia for over 12 hours had significantly higher odds of replantation success than the amputated digits replanted with 0-12 hours of warm ischemia time ( P ≤ 0.05). The odds of survival in the early (0-6 hours) replantation group were around 40% greater than the later (6-12 hours) replantation group ( P ≤ 0.05). Secondary outcomes that were associated with higher survival rates included a clean-cut amputation, increased venous and arterial anastomosis, a repair that did not require a vein graft, and replants performed in nonsmokers ( P ≤ 0.05). DISCUSSION: Overall, these findings suggest that when predicting digit replantation success, time is of the essence when the digit has yet to be preserved in a cold environment. This benefit, however, is almost completely diminished when the amputated digit is appropriately maintained in a cold environment soon after injury. In conclusion, our results suggest that there is potential for broadening the ischemia time limits for digit replant survival outlined in the literature, particularly for digits that have been stored correctly in cold ischemia.

Surgical choice for the treatment of partial intestinal ischemic necrosis caused by acute type a aortic dissection combined with malperfusion of superior mesenteric artery.

Acute type A aortic dissection is a severe cardiovascular disease characterized by rapid onset and high mortality. Traditionally, urgent open aortic repair is performed after admission to prevent aortic rupture and death. However, when combined with malperfusion syndrome, the low perfusion of the superior mesenteric artery can further lead to intestinal necrosis, significantly impacting the surgery's prognosis and potentially resulting in adverse consequences, bringing. This presents great significant challenges in treatment. Based on recent domestic and international research literature, this paper reviews the mechanism, current treatment approaches, and selection of surgical methods for poor organ perfusion caused by acute type A aortic dissection. The literature review findings suggest that central aortic repair can be employed for the treatment of acute type A aortic dissection with inadequate perfusion of the superior mesenteric artery. The superior mesenteric artery can be windowed and (/or) stented, followed by delayed aortic repair. Priority should be given to revascularization of the superior mesenteric artery, followed by central aortic repair. During central aortic repair, direct blood perfusion should be performed on the distal true lumen of the superior mesenteric artery, leading to resulting in favorable therapeutic outcomes. The research results indicate that even after surgical aortic repair, intestinal ischemic necrosis may still occur. In such cases, prompt laparotomy and necessary necrotic bowel resection are crucial for saving the patient's life.

Gold Nanorod-Loaded Nano-Contrast Agent with Composite Shell-Core Structure for Ultrasonic/Photothermal Imaging-Guided Therapy in Ischemic Muscle Disorders.

Purpose: This study aims to broaden the application of nano-contrast agents (NCAs) within the realm of the musculoskeletal system. It aims to introduce novel methods, strategies, and insights for the clinical management of ischemic muscle disorders, encompassing diagnosis, monitoring, evaluation, and therapeutic intervention. Methods: We developed a composite encapsulation technique employing O-carboxymethyl chitosan (OCMC) and liposome to encapsulate NCA-containing gold nanorods (GNRs) and perfluoropentane (PFP). This nanoscale contrast agent was thoroughly characterized for its basic physicochemical properties and performance. Its capabilities for in vivo and in vitro ultrasound imaging and photothermal imaging were authenticated, alongside a comprehensive biocompatibility assessment to ascertain its effects on microcirculatory perfusion in skeletal muscle using a murine model of hindlimb ischemia, and its potential to augment blood flow and facilitate recovery. Results: The engineered GNR@OCMC-liposome/PFP nanostructure exhibited an average size of 203.18±1.49 nm, characterized by size uniformity, regular morphology, and a good biocompatibility profile. In vitro assessments revealed NCA's potent photothermal response and its transformation into microbubbles (MBs) under near-infrared (NIR) irradiation, thereby enhancing ultrasonographic visibility. Animal studies demonstrated the nanostructure's efficacy in photothermal imaging at ischemic loci in mouse hindlimbs, where NIR irradiation induced rapid temperature increases and significantly increased blood circulation. Conclusion: The dual-modal ultrasound/photothermal NCA, encapsulating GNR and PFP within a composite shell-core architecture, was synthesized successfully. It demonstrated exceptional stability, biocompatibility, and phase transition efficiency. Importantly, it facilitates the encapsulation of PFP, enabling both enhanced ultrasound imaging and photothermal imaging following NIR light exposure. This advancement provides a critical step towards the integrated diagnosis and treatment of ischemic muscle diseases, signifying a pivotal development in nanomedicine for musculoskeletal therapeutics.

Enhanced external counterpulsation treatment improves multi-organ hemodynamics for postoperative liver transplantation patient. A case report.

INTRODUCTION: Post liver transplantation (LT) patients endure high morbidity rate of multi-organ ischemic symptoms following reperfusion. We hypothesize that enhanced external counterpulsation (EECP) as a typical non-invasive assisted circulation procedure, which can efficiently inhibit the relative ischemic symptoms via the systemic improvement of hemodynamics. CASE PRESENTATION: A 51-year-old male patient, 76 kg, 172 cm, received orthotopic LT surgery for viral hepatitis B induced acute-on-chronic liver failure hepatic failure. His medical records revealed ischemic symptoms in multi-organ at the time of hospital discharge, including headache, refractory insomnia, abdominal paralysis, and lower limb pain. The EECP treatment was introduced for assisted rehabilitation and to improve the postoperative quality of life. Doppler Ultrasound examination showed significant augmentation of blood flow volume in the carotid arteries, the hepatic artery, the portal vein and the femoral artery during EECP intervention. A standard 35-hour EECP treatment led to significant improvement in quality of life, e.g. sleep quality and walking ability. CONCLUSION: We report a case of multi-organ ischemic symptoms in a post LT patient. EECP treatment can significantly improve the quality of life via the systematic promotion of hemodynamics.

Acute Glaucoma Following Internal Carotid Artery Stenting: A Rare But Serious Complication of Ocular Ischemic Syndrome.

Acute glaucoma following carotid artery recanalization is a rare but severe complication of underlying ocular ischemic syndrome. We present a case of a 71-year-old woman with ocular ischemic syndrome and severe stenosis of the right internal and external carotid artery undergoing carotid artery stenting. Immediate postprocedural angiography showed pronounced reperfusion of the ophthalmic artery. Subsequently, the patient developed vision-threatening acute glaucoma despite treatment with acetazolamide. Monitoring of intraocular pressure is important in patients who are at risk of developing ocular ischemic syndrome because of internal carotid artery stenosis. Interventionalists should also assess the degree of vascular collateralization from the external carotid artery.

Understanding delays in chronic limb-threatening ischaemia care: Application of the theoretical domains framework to identify factors affecting primary care clinicians' referral behaviours.

INTRODUCTION: Patients in the community with suspected Chronic limb-threatening ischaemia (CLTI) should be urgently referred to vascular services for investigation and management. The Theoretical Domains Framework (TDF) allows identification of influences on health professional behaviour in order to inform future interventions. Here, the TDF is used to explore primary care clinicians' behaviours with regards to recognition and referral of CLTI. METHODS: Semi-structured interviews were conducted with 20 podiatrists, nurses and general practitioners in primary care. Directed content analysis was performed according to the framework method. Utterances were coded to TDF domains, and belief statements were defined by grouping similar utterances. Relevance of domains was confirmed according to belief frequency, presence of conflicting beliefs and the content of the beliefs indicating relevance. RESULTS: Nine TDF domains were identified as relevant to primary care clinicians: Knowledge, Environmental context and resources, Memory, Decision and attention processes, Beliefs about capabilities, Skills, Emotions, Reinforcement and Behavioural regulation. Relationships across domains were identified, including how primary care clinician confidence and working in a highly pressurized environment can affect behaviour. CONCLUSION: We have identified key barriers and enablers to timely recognition and referral behaviour. These beliefs identify targets for theory-driven behaviour change interventions to reduce delays in CLTI pathways.

A fluctuating intensity of care: A qualitative study on the experiences of informal caregivers of patients with critical limb-threatening ischemia.

Informal caregivers play a significant role in providing care for older, often vulnerable, patients, and supporting them as they live with chronic diseases. Due to the rising prevalence of older vascular patients and their use of healthcare, the role of their informal caregivers will become more important. However, little is known about the experiences of informal caregivers of patients with critical limb-threatening ischemia and the impact of informal care on different aspects of these caregivers' lives. In addition, literature does not describe the burden this role brings with it, or lack thereof. Therefore a qualitative study using a phenomenological approach, specifically interpretive phenomenological analysis, was used to gain insight into the experiences of the primary informal caregivers of patients with chronic limb-threatening ischemia. Data were collected via semi-structured interviews and focus groups discussions. Fifteen primary informal caregivers of patients with critical limb-threatening ischemia under the care of the vascular surgeon at a tertiary teaching hospital in the Netherlands were included. Data analysis yielded three themes: the perceived identity of this group of caregivers; the varying intensity of informal care; and the collaboration between informal carers, their care recipients and the professional care provider within the vascular surgery department. In contrast to carers of other chronic diseases, the shifting intensity of care that informal caregivers of critical limb-threatening ischemia patients experience seems to prevent long-term overload. Adapting to that fluctuating situation requires flexibility from healthcare providers within the vascular surgery department. In addition, professionals need to involve informal caregivers in the patient's decision-making process and recognize their role in that process.

Dulaglutide restores endothelial progenitor cell levels in diabetic mice and mitigates high glucose-induced endothelial injury through SIRT1-mediated mitochondrial fission.

Type 2 diabetes mellitus (T2DM) significantly impairs the functionality and number of endothelial progenitor cells (EPCs) and resident endothelial cells, critical for vascular repair and regeneration, exacerbating the risk of vascular complications. GLP-1 receptor agonists, like dulaglutide, have emerged as promising therapeutic agents due to their multifaceted effects, including the enhancement of EPC activity and protection of endothelial cells. This study investigates dulaglutide's effects on peripheral blood levels of CD34+ and CD133+ cells in a mouse model of lower limb ischemia and its protective mechanisms against high-glucose-induced damage in endothelial cells. Results demonstrated that dulaglutide significantly improves blood flow, reduces tissue damage and inflammation in ischemic limbs, and enhances glycemic control. Furthermore, dulaglutide alleviated high-glucose-induced endothelial cell damage, evident from improved tube formation, reduced reactive oxygen species accumulation, and restored endothelial junction integrity. Mechanistically, dulaglutide mitigated mitochondrial fission in endothelial cells under high-glucose conditions, partly through maintaining SIRT1 expression, which is crucial for mitochondrial dynamics. This study reveals the potential of dulaglutide as a therapeutic option for vascular complications in T2DM patients, highlighting its role in improving endothelial function and mitochondrial integrity.

Alternative vein bypass in octogenarians with chronic limb-threatening ischaemia.

BACKGROUND: Octogenarians are regarded as one of the frailest patient groups among the chronic limb-threatening ischaemia population with high perioperative morbidity and mortality rates. As a result, alternative vein bypass surgery in the absence of sufficient great saphenous vein is often not considered as a potential treatment option. The aim of this study was to compare the results of octogenarians undergoing alternative vein bypass surgery due to chronic limb-threatening ischaemia to younger patients. METHODS: A single-centre retrospective analysis of patients undergoing bypass surgery for chronic limb-threatening ischaemia with alternative autologous vein grafts between 1997 and 2018 was performed. Patients aged over 80 years were compared with those under 80 years. Graft patency rates were assessed and a risk factor analysis for limb loss was performed. RESULTS: In total, 592 patients underwent bypass surgery during the study interval. Twenty-one per cent (n = 126) of patients were 80 years or older. At 4 years, primary, primary-assisted and secondary patency as well as limb salvage rates were not significantly different between the two groups (46% versus 50%, 60% versus 66%, 69% versus 72%, 72% versus 77%, for octogenarians versus non-octogenarians respectively). Major amputations were performed in 27 (21%) octogenarians and 91 (20%) non-octogenarians (P = 0.190). No higher 30-day and long-term mortality rates nor morbidity rates were detected in the octogenarian group with a median follow-up time of 27 (interquartile range 12-56) months. Minor amputation, the reason for alternative vein grafts, as well as the profunda femoris artery as proximal origin of the bypass were risk factors for limb loss in the postoperative course. CONCLUSION: Alternative vein bypass surgery in octogenarians with chronic limb-threatening ischaemia is safe and effective in terms of patency rates, limb salvage and survival compared with younger patients in the absence of sufficient great saphenous vein. Age alone should not be a deterrent from performing bypass surgery.

miR-709 exerts an angiogenic effect through a FGF2 upregulation induced by a GSK3B downregulation.

The aim of this study was to identify angiogenic microRNAs (miRNAs) that could be used in the treatment of hindlimb ischemic tissues. miRNAs contained in extracellular vesicles (EVs) deriving from the plasma were analyzed in C57BL/6 mice, which have ischemia tolerance, and in BALB/c mice without ischemia tolerance as part of a hindlimb ischemia model; as a result 43 angiogenic miRNA candidates were identified. An aortic ring assay was employed by using femoral arteries isolated from BALC/c mice and EVs containing miRNA; as a result, the angiogenic miRNA candidates were limited to 14. The blood flow recovery was assessed after injecting EVs containing miRNA into BALB/c mice with hindlimb ischemia, and miR-709 was identified as a promising angiogenic miRNA. miR-709-encapsulating EVs were found to increase the expression levels of the fibroblast growth factor 2 (FGF2) mRNA in the thigh tissues of hindlimb ischemia model BALB/c mice. miR-709 was also found to bind to the 3'UTR of glycogen synthase kinase 3 beta (GSK3B) in three places. GSK3B-knockdown human artery-derived endothelial cells were found to express high levels of FGF2, and were characterized by increased cell proliferation. These findings indicate that miR-709 induces an upregulation of FGF2 through the downregulation of GSK3B.

Documentary analysis of national and international guidance for community clinicians referring patients with suspected chronic limb-threatening ischaemia.

BACKGROUND: Delayed referral of patients with chronic limb-threatening ischaemia (CLTI) from the community to vascular services may increase risk of amputation due to delayed revascularisation. Lack of appropriate guidance for clinicians in the community may contribute to this problem. This documentary analysis investigated referral guidance available to primary care clinicians. METHODS: National and international documents providing guidance on CLTI management were identified by searching sources including Medline, Embase, Guidelines International Network and College/Society websites. Data were extracted on referral recommendations, target audience and author groups. Recommendations were coded according to the Behaviour Change Technique Taxonomy. Clinical practice guideline quality and ease of implementation were assessed independently by two reviewers using the Appraisal of Guidelines Research and Evaluation (AGREE) II and Guideline Implementability Appraisal (GLIA) tools, respectively. RESULTS: 12 documents containing guidance on CLTI referrals were included. Five were clinical practice guidelines. Nine targeted clinicians in the community among their audience, yet only one included a primary care clinician in their author group. Recommendations on identification and referral of CLTI were often in non-specific language and frequently assumed specialist knowledge of vascular disease. Just 4 of the 93 behaviour change techniques were identified in the guidance documents. Three relevant domains of the AGREE II tool were scored for five clinical practice guidelines: stakeholder involvement (range 21.4%-52.4%, mean 42.9%), clarity of presentation (range 71.4%-92.9%, mean 82.9%) and applicability (25.0%-57.1%, mean 36.8%). The GLIA tool identified barriers to ease of implementation for all five clinical practice guidelines. CONCLUSIONS: Most guidance for clinicians in the community on the management of CLTI has been written without their input and assumes knowledge of vascular disease, which may be lacking. Future guidance development should involve community clinicians, consider using additional behaviour change techniques, and improve the applicability and ease of implementation of recommendations.

Mitochondrial transfer mediates endothelial cell engraftment through mitophagy.

Ischaemic diseases such as critical limb ischaemia and myocardial infarction affect millions of people worldwide1. Transplanting endothelial cells (ECs) is a promising therapy in vascular medicine, but engrafting ECs typically necessitates co-transplanting perivascular supporting cells such as mesenchymal stromal cells (MSCs), which makes clinical implementation complicated2,3. The mechanisms that enable MSCs to facilitate EC engraftment remain elusive. Here we show that, under cellular stress, MSCs transfer mitochondria to ECs through tunnelling nanotubes, and that blocking this transfer impairs EC engraftment. We devised a strategy to artificially transplant mitochondria, transiently enhancing EC bioenergetics and enabling them to form functional vessels in ischaemic tissues without the support of MSCs. Notably, exogenous mitochondria did not integrate into the endogenous EC mitochondrial pool, but triggered mitophagy after internalization. Transplanted mitochondria co-localized with autophagosomes, and ablation of the PINK1-Parkin pathway negated the enhanced engraftment ability of ECs. Our findings reveal a mechanism that underlies the effects of mitochondrial transfer between mesenchymal and endothelial cells, and offer potential for a new approach for vascular cell therapy.

The Utility of Prevena Negative Pressure Wound Therapy on Groin Incisions for Critical Limb-Threatening Ischemia: A Single Institution Experience.

BACKGROUND: Incisional negative pressure wound therapy (iNPWT) is an adjunctive treatment that uses constant negative pressure suction to facilitate healing. The utility of this treatment modality on vascular operations for critical limb-threatening ischemia (CLTI) has yet to be elucidated. This study compares the incidence of postoperative wound complications between the Prevena Incision Management System, a type of iNPWT, and standard wound dressings for vascular patients who also underwent plastic surgery closure of groin incisions for CLTI. METHOD: We performed a retrospective cohort study of 40 patients with CLTI who underwent 53 open vascular surgeries with subsequent sartorius muscle flap closure. Patient demographics, intraoperative details, and wound complications were measured from 2015 to 2018 at the University of California San Francisco. Two cohorts were generated based on the modality of postoperative wound management and compared on wound healing outcomes. RESULTS: Of the 53 groin incisions, 29 were managed with standard dressings, and 24 received iNPWT. Patient demographics, comorbidities, and operative characteristics were similar between the 2 groups. Patients who received iNPWT had a significantly lower rate of infection (8.33% vs 31.0%, P = 0.04) and dehiscence (0% vs 41.3%, P < 0.01). Furthermore, the iNPWT group had a significantly lower rate of reoperation (0% vs 17.2%, P = 0.03) for wound complications within 30 days compared with the control group and a moderately reduced rate of readmission (4.17% vs 20.7%, P = 0.08). CONCLUSIONS: Rates of infection, reoperation, and dehiscence were significantly reduced in patients whose groin incisions were managed with iNPWT compared with standard wound care. Readmission rates were also decreased, but this difference was not statistically significant. Our results suggest that implementing iNPWT for the management of groin incisions, particularly in patients undergoing vascular operations for CLTI, may significantly improve clinical outcomes.

Infrapopliteal Bypass In Patients On Dialysis: Patency And Survival.

INTRODUCTION: Portugal has one of the highest prevalence of patients on a regular dialysis program. This population has a higher incidence of peripheral arterial disease with higher rates of postoperative morbidity and mortality. Our goal was to compare outcomes between dialysis and non-dialysis patients with chronic limb threatening ischemia (CLTI) submitted to infrapopliteal bypass. MATERIALS AND METHODS: A retrospective single-center study of infrapopliteal bypass for CLTI was performed between 2012 and 2019. Patients were divided in two groups based on dialysis status (group 1 incorporated patients on dialysis). Primary end point was 1-year freedom from CLTI. Secondary end points were limb-salvage, survival and primary (PP) and tertiary patency (TP) rates at 3 years of follow-up. RESULTS: A total of 352 infrapopliteal bypasses were performed in 310 patients with CLTI. Fourteen percent of the revascularizations were performed on dialysis patients (48/352). Median age was 73 years (interquartile range - IQR 15) and 74% (259/352) were male. Median follow-up was 26 months (IQR 42). Overall, 92% (325/352) had tissue loss and 44% (154/352) had some degree of infection. The majority of revascularization procedures were performed with vein grafts (61%, 214/352). The 30-day mortality was 4% (11/310), with no difference between groups (p = 0.627). Kaplan-Meier analysis showed no difference between groups regarding freedom from CLTI (76% vs. 79%; HR 0.96, CI 0.65-1.44, p=0.857), limb-salvage (70% vs. 82%; HR 1.40, CI 0.71-2.78, p=0.327) and survival (62% vs. 64%; HR 1.08, CI 0.60-1.94, p=0.799). PP rates were 39% in group 1 and 64% in group 2 (HR 1.71, CI 1.05-2.79, p=0.030). TP rates were not different between groups (57% and 78%; HR 1.79, CI 0.92-3.47, p=0.082). CONCLUSION: Infrapopliteal bypass for CLTI, on dialysis patients, resulted in lower PP rates. No differences were observed in freedom from CLTI, TP, limb salvage and survival.

Dexmedetomidine protects the uterus against ischemia-reperfusion injury in rats.

OBJECTIVE: This study aimed to analyze the histopathological and biochemical effects of dexmedetomidine on the rat uteri exposed to experimental ischemia-reperfusion injury. MATERIALS AND METHODS: Twenty-four female rats were randomly divided into three groups. Group 1 was defined as the control group. An experimental uterine ischemia-reperfusion model was created in Group 2. Group 3 was assigned as the treatment group. Similar uterine ischemia-reperfusion models were created for the rats in Group 3, and then, unlike the other groups, 100 µg/kg of dexmedetomidine was administered intraperitoneally immediately after the onset of reperfusion. In blood biochemical analysis, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and malondialdehyde (MDA), interleukin 1beta (IL-1ß), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels were measured. In the histopathological analyses, endometrial epithelial glandular changes (leukocytosis, cell degeneration) and endometrial stromal changes (congestion, edema) were analyzed using the tissue damage scoring system. RESULTS: It was observed that IL-1ß, IL-6, and TNF-α levels were significantly suppressed in Group 3 compared to Group 2 (p=0.001, p<0.001 and p=0.001, respectively). MDA level was noted as the highest in Group 2. The MDA value in Group 3 was measured at 5.37±0.82, which was significantly decreased compared to Group 2 (p<0.001). An increase in antioxidant enzyme activities (SOD and GSH-PX) was observed in Group 3 compared to Group 2 (p=0.001 and p=0.006, respectively). In our histopathological analysis, a significant improvement in endometrial epithelial glandular and endometrial stromal changes was revealed in Group 3 compared to Group 2 (p<0.001). CONCLUSIONS: In our study, it has been documented that dexmedetomidine protects the uterine tissue against ischemia-reperfusion injury.

Treatment with RNase alleviates brain injury but not neuroinflammation in neonatal hypoxia/ischemia.

There is a need for new treatments to reduce brain injuries derived from neonatal hypoxia/ischemia. The only viable option used in the clinic today in infants born at term is therapeutic hypothermia, which has a limited efficacy. Treatments with exogenous RNase have shown great promise in a range of different adult animal models including stroke, ischemia/reperfusion injury, or experimental heart transplantation, often by conferring vascular protective and anti-inflammatory effects. However, any neuroprotective function of RNase treatment in the neonate remains unknown. Using a well-established model of neonatal hypoxic/ischemic brain injury, we evaluated the influence of RNase treatment on RNase activity, gray and white matter tissue loss, blood-brain barrier function, as well as levels and expression of inflammatory cytokines in the brain up to 6 h after the injury using multiplex immunoassay and RT-PCR. Intraperitoneal treatment with RNase increased RNase activity in both plasma and cerebropinal fluids. The RNase treatment resulted in a reduction of brain tissue loss but did not affect the blood-brain barrier function and had only a minor modulatory effect on the inflammatory response. It is concluded that RNase treatment may be promising as a neuroprotective regimen, whereas the mechanistic effects of this treatment appear to be different in the neonate compared to the adult and need further investigation.