Vascular Disturbances Research Articles

Prenatal stress-induced increases in hippocampal von Willebrand factor expression are prevented by concurrent prenatal escitalopram

Prenatal stress has been linked to deficits in neurological function including deficient social behavior, alterations in learning and memory, impaired stress regulation, and susceptibility to adult disease. In addition, prenatal environment is known to alter cardiovascular health; however, limited information is available regarding the cerebrovascular consequences of prenatal stress exposure. Vascular disturbances late in life may lead to cerebral hypoperfusion which is linked to a variety of neurodegenerative and psychiatric diseases. The known impact of cerebrovascular compromise on neuronal function and behavior highlights the importance of characterizing the impact of stress on not just neurons and glia, but also cerebrovasculature. Von Willebrand factor has previously been shown to be impacted by prenatal stress and is predictive of cerebrovascular health. Here we assess the impact of prenatal stress on von Willebrand factor and related angiogenic factors. Furthermore, we assess the potential protective effects of concurrent anti-depressant treatment during in utero stress exposure on the assessed cerebrovascular endpoints. Prenatal stress augmented expression of von Willebrand factor which was prevented by concurrent in utero escitalopram treatment. The functional implications of this increase in von Willebrand factor remain elusive, but the presented data demonstrate that although prenatal stress did not independently impact total vascularization, exposure to chronic stress in adulthood decreased blood vessel length. In addition, the current study demonstrates that production of reactive oxygen species in the hippocampus is decreased by prenatal exposure to escitalopram. Collectively, these findings demonstrate that the prenatal experience can cause complex changes in adult cerebral vascular structure and function.

Benign hepatocellular nodules of healthy liver: focal nodular hyperplasia and hepatocellular adenoma

Owing to the progress of imaging techniques, benign hepatocellular nodules are increasingly discovered in the clinical practice. This group of lesions mostly arises in the context of a putatively normal healthy liver and includes either pseudotumoral and tumoral nodules. Focal nodular hyperplasia and hepatocellular adenoma are prototypical examples of these two categories of nodules. In this review we aim to report the main pathological criteria of differential diagnosis between focal nodular hyperplasia and hepatocellular adenoma, which mainly rests upon morphological and phenotypical features. We also emphasize that for a correct diagnosis the clinical context such as sex, age, assumption of oral contraceptives, associated metabolic or vascular disturbances is of paramount importance. While focal nodular hyperplasia is a single entity epidemiologically more frequent than adenoma, the latter is representative of a more heterogeneous group which has been recently and extensively characterized from a clinical, morphological, phenotypical and molecular profile. The use of the liver biopsy in addition to imaging and the clinical context are important diagnostic tools of these lesions. In this review we will survey their systematic pathobiology and propose a diagnostic algorithm helpful to increase the diagnostic accuracy of not dedicated liver pathologists. The differential diagnosis between so-called typical and atypical adenoma and well differentiated hepatocellular carcinoma will also be discussed.

Physiology in Medicine: neuromuscular consequences of diabetic neuropathy.

Diabetic polyneuropathy (DPN) refers to peripheral nerve dysfunction as a complication of diabetes mellitus. This condition is relatively common and is likely a result of vascular and/or metabolic disturbances related to diabetes. In the early or less severe stages of DPN it typically results in sensory impairments but can eventually lead to major dysfunction of the neuromuscular system. Some of these impairments may include muscle atrophy and weakness, slowing of muscle contraction, and loss of power and endurance. Combined with sensory deficits these changes in the motor system can contribute to decreased functional capacity, impaired mobility, altered gait, and increased fall risk. There is no pharmacological disease-modifying therapy available for DPN and the mainstay of treatment is linked to treating the diabetes itself and revolves around strict glycemic control. Exercise therapy (including aerobic, strength, or balance training-based exercise) appears to be a promising preventative and treatment strategy for patients with DPN and those at risk. The goal of this Physiology in Medicine article is to highlight important and overlooked dysfunction of the neuromuscular system as a result of DPN with an emphasis on the physiologic basis for that dysfunction. Additionally, we sought to provide information that clinicians can use when following patients with diabetes or DPN including support for the inclusion of exercise-based therapy as an effective, accessible, and inexpensive form of treatment.

CLINICAL SIGNIFICANCE OF EXTRACORPOREAL PHOTOCHEMOTHERAPY IN COMPLEX TREATMENT OF LOCALIZED SCLERODERMA

Background: Scleroderma is an autoimmune disease with progressing lesions of connective tissue where fibrosclerotic and vascular disturbances prevail. Lacking of the united concept of its pathogenesis significantly hampers elaboration of pathogenetic methods of treatment. Conventional methods of treatment of localized scleroderma have insufficient clinical effectiveness, lead to remission of short duration, have a series of side effects and complications. Aim: To raise the efficiency of the focal scleroderma treatment with a complex therapy including a method of extracorporeal photochemotherapy (EPCT). Materials and methods: A total of 19 patients with plaque or linear types of localized scleroderma underwent complex treatment including EPCT. All patients had a steadfast progressing course of the disease with generalized lesions, the signs of early systemic scleroderma being revealed in 3 of them. EPCT-method is based on the photo-sensitizing effect of 8-methoxypsoralene and ultraviolet А radiation of mononuclear cells which were separated using cytopheresis further followed with reinfusion. Every course included 4 exposures implemented every other day. Repeated therapeutic course was set in 3 months. Results: All patients satisfactorily tolerated EPCT procedure without side effects and complications. After 3 therapeutic courses, the disease progression was arrested in all patients, the density of scleroderma foci was diminished, approximately, by 50% as compared to the initial level. The crown of the peripheral growth completely disappeared, and the sizes of the disease foci decreased. The more pronounced clinical effect was achieved in patients with disease duration not exceeding 3 years. Conclusion: The proposed method was efficient in treatment of localized scleroderma and might be applied as an adjuvant therapy.

Effectiveness of homeopathic remedies in severe laminitic horses

Background : Equine laminitis is a severe inflammation of the internal lamellar of the horse foot due to an alteration of the periferic vascular flood flow. Marked vascular disturbances occur and microtrombi form in the digital vasculature, which is primed for neutrophil invasion and activation. Endotoxin exarcebate endothelial cell dysfunction, increasing endothelin-I and reducing Endothelial Nitrix Oxide Synthase (eNOS) activity. Ischaemic and inflammatory stimuli could also activate MMPs, leading to digital failure: destruction of the basement membrane bonding the interlocking lamellar leaflets, leads to detachment of phalanx bone from the hoof wall. Ischemia (I) triggers an inflammatory response that precipitates cell death during reperfusion (R). Nitric Oxide (NO) is an inflammatory mediator produced by macrophages and neutrophils during the inflammatory response. It is synthesised via oxidation of L-Arginine by Nitric Oxide Synthetase and plays an ambiguous role during I/R. Additionally, NO mediates the activation of Soluble Guanylyl Cyclase, which can also be activated by endogenous Carbon Monoxide (CO). Metabolism of heme and lipid peroxidation, which generate CO, are both enhanced during inflammation. Methods : 5 horses (4 mares and 1 stallion) diagnosed with acute severe laminitis were treated with homeopathic remedies; 10 healthy horses were selected to determine whether homeopathic remedies are useful and safe as a treatment for equine laminitis, if the level of NO can be re-established and the role of CO. Laminitic horses were administered oral homeopathic treatment only: Aconitum 30ch, Apis 15ch, Arnica 7ch, Belladonna 9ch, Bryonia 9ch and Nux vomica 9ch – 2 granules of each remedy every hour, 10 times per day for 10 days. Variables evaluated included signs of pain, grade of lameness, digital pulse, NO, Nitric Oxide Synthetase Expression, CO and Hemeoxygenase Expression in plasma levels. Results : Homeopathy-treated horses showed an obvious improvement after one day of treatment. Clinical signs of the disease (pain, severe lameness) had completely disappeared at the third day without side effects. NO diminished in laminitis has significant recovery levels in mares. CO and HO-1 levels were higher than in healthy horses.

Sexuality in overweight and obesity

The association between obesity and sexual dysfunction has been described in many studies. Neurobiological, hormonal, vascular and mental disturbances are the main reasons in male and in female gender. Sexual interest and desire, sexual arousal, orgasm, painful intercourse and premature ejaculation can be involved. Data for prevalence of sexual function disturbances in obese people are scarce and most studies were small. For screening of sexual function we recommend the International Index of Erectile Function (IIEF)-Score, which contains 15 Items for males and the Female Sexual Function Index (FSFI), which contains 19 items for females. Treatment of sexual function disturbances include lifestyle changes with an increase of physical activity, weight control, healthy eating and smoking cessation. Testosterone substitution in cases of real hypogonadism and treatment with PDE-5 inhibitors are well documented treatment options in male individuals. New treatment options for female patients with variable effectiveness are fibanserin, testosterone, bupropione and oxytocin.

Clinical Features and Prognosis of Sudden Sensorineural Hearing Loss Secondary to Intralabyrinthine Hemorrhage.

Background and ObjectivesA number of etiologies of idiopathic sudden sensorineural hearing loss (ISSNHL) have been proposed, including viral infection, vascular disturbance, and immune-mediated mechanisms. Intralabyrinthine hemorrhage (ILH) as a cause of SSNHL is extremely rare, and there have been no studies defining the characteristics of hearing impairment and prognosis in patients with ISSNHL due to ILH. This study aimed to investigate the difference in impaired hearing patterns and prognosis for hearing recovery between patients with ISSNHL due to ILH confirmed by magnetic resonance imaging (MRI) and sex- and age-matched patients with ISSNHL due to causes other than ILH.Subjects and MethodsWe compared the results of audiometry and MRI in 12 patients who had ILH on MRI (hemorrhage group) and in 23 sex- and age-matched controls without abnormal findings related to their hearing loss on MRI (non-hemorrhage group). Initial hearing impairment, progression, and recovery of hearing loss were compared between the two groups.ResultsA majority of patients (92%) in the hemorrhage group complained of dizziness. Initial hearing impairment was more frequent in the hemorrhage group than in the non-hemorrhage group (94.09±35.9 vs. 66.66±30.1, p-value=0.036). The final recovery threshold in the hemorrhage group was worse (78.19±46.26 vs. 37.17±31.96, p-value=0.014) than that in the non-hemorrhage group. In the hemorrhage group, hearing recovery seemed to occur less often at high frequencies (2,000, 4,000, and 8,000 Hz) than at low frequencies (250, 500, and 1,000 Hz).ConclusionsThe presence of ILH was associated with poor hearing prognosis and the occurrence of vertigo. The abrupt onset of hearing loss associated with vertigo and the presence of hyperresonance on fat-suppressed T1-weighted MRI images of labyrinthic fluid strongly suggests acute intralabyrinthine hemorrhage, and is predictive of considerable hearing impairment and poor prognosis.

Pathogenetic approaches to treatment of cognitive disorders in patients with diabetes mellitus

The article presents the currents concepts on the mechanisms of brain lesions and development of cognitive impairment in diabetes mellitus (DM) including DM type 2. Metabolic and vascular mechanisms, oxidative stress, hyperglycemia, glutamate excitotoxicity, insulin insufficiency and brain insulin resistance, general vascular and microcirculatory disturbances, death of cortical neurons, decrease in the newly synthesized acetylcholine, activation of lipid peroxidation are considered. A review of the main domestic and international drugs used in clinical practice for treatment of cognitive impairment in patients with DM is presented.

Antioxidant Effects of Sheep Whey Protein on Endothelial Cells

Excessive production of reactive oxygen species (ROS) may cause endothelial dysfunction and consequently vascular disease. In the present study, the possible protective effects of sheep whey protein (SWP) from tert-butyl hydroperoxide- (tBHP-) induced oxidative stress in endothelial cells (EA.hy926) were assessed using oxidative stress biomarkers. These oxidative stress biomarkers were glutathione (GSH) and ROS levels determined by flow cytometry. Moreover, thiobarbituric acid-reactive substances (TBARS), protein carbonyls (CARB), and oxidized glutathione (GSSG) were determined spectrophotometrically. The results showed that SWP at 0.78, 1.56, 3.12, and 6.24 mg of protein mL−1 increased GSH up to 141%, while it decreased GSSG to 46.7%, ROS to 58.5%, TBARS to 52.5%, and CARB to 49.0%. In conclusion, the present study demonstrated for the first time that SWP protected endothelial cells from oxidative stress. Thus, SWP may be used for developing food supplements or biofunctional foods to attenuate vascular disturbances associated with oxidative stress.

Патоморфологические изменения пульпы зубов при экспериментальном остеопорозе

The study focused on pathomorphological changes taking place in the tooth pulp in sheep in case of experimental osteoporosis. The pulp was extracted after cracking the teeth. The sections were stained with hematoxylin and eosin by Masson, and impregnated with silver by Foot and Bielschowsky-Gros. There were severe vascular disturbances detected (vasodilation, stasis, perivascular edema with cell infiltration, hemorrhages), which resulted in vacuolization of odontoblasts, pulp reticular dystrophy, disintegration of argyrophilic and nerve structures. Such disturbances came along with proliferation of cell elements in the connective tissue and in nerve elements with denticle development.

The Propagation of Hemophilic Arthropathy - the Role of Abnormal Angiogenesis and Vascular Remodeling in Recurrent Joint Bleeding in Adults with Hemophilia

Neoangiogenesis and vascular remodeling in the hypertrophic synovium of arthropathic hemophilic joints may disturb vascular integrity and contribute to repeated bleeding (A von Drygalski, et al. Vascular Remodeling Underlies Re-Bleeding in Hemophilic Arthropathy; ASH 2015; Abstract ID 78677). However, it is difficult to distinguish the importance of the contribution of abnormal vascular structures to hemophilic joint bleeding from the contribution of low clotting factor levels. This is because most prophylactic clotting factor replacement strategies are designed to avoid trough levels below 1-5%, but not to fully correct the factor deficiency.This report reveals the importance of aberrant angiogenesis for joint bleeding in two hemophilia patients whose clotting factor activity levels were constantly normal or near normal. The first patient had severe Hemophilia A with normalized Factor (f)VIII activity levels after liver transplantation 6 years previously. Abnormal vascularization of elbows, knees and ankles (absent bleeding) was detected by musculoskeletal ultrasound and Power Doppler (PD). Three months after the baseline exam the patient experienced severe elbow bleeding associated with new vascular changes on PD. These changes were characterized by pronounced confluent, patchy vascular signals and numerous enlarged and thickened vessels by angiography consistent with acute and chronic vascular remodeling. Bleeding could not be controlled by increasing fVIII activity to supra-normal levels, and ultimately required synovial embolization. The second patient has severe Hemophilia B and presented shortly after left knee joint replacement with fluctuating knee bleeding for many months associated with pronounced dynamic vascular changes on PD. Neither bleeding nor vascular changes were prevented by daily fIX treatment which maintained near normal plasma fIX activity levels. Within one year, additional chronic bleeding with vascular changes developed in the left elbow and left ankle and remained unresponsive to intense factor replacement.These cases provide several insights. First, vascular changes in hemophilic arthropathy persist and evolve in dynamic fashion even in the presence of normal clotting factor activities. Second, vascular disturbance and leakiness contributed to bleeding independent of clotting factor activity levels as exemplified by the first patient and as suggested by the second patient. Third, the sequence of bleeding events in the second patient suggests that at least some of the observed vascular abnormalities are mediated systemically. These observations provide clinical evidence in support of the hypothesis that neoangiogenesis and vascular remodeling contribute to hemophilic joint bleeding and should lead to new studies of the pathophysiology of vascular remodeling in such joints. Targeting angiogenesis may emerge as a new treatment strategy to enhance the effectiveness of clotting factor replacement hemophilic arthropathy. DisclosuresChang:Biogen: Research Funding. Rose:Sirtex Medical: Equity Ownership, Honoraria; XLSciTech: Consultancy; Surefire Medical: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Embolx: Consultancy. von Drygalski:Baxalta: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biogen: Honoraria, Research Funding; Hematherix Inc: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Modifiable risk factors for erectile dysfunction: an assessment of the awareness of such factors in patients suffering from ischaemic heart disease.

Up to 40% of cases of erectile dysfunction (ED) originate from vascular disturbances associated with atherosclerotic disease, leading to the previously proven concomitance between ischaemic heart disease (IHD) and ED. The aim of this study was to evaluate patients' knowledge about modifiable risk factors for ED. The evaluated group of patients was composed of 502 male patients undergoing cardiac rehabilitation and receiving treatment for IHD. The patients' knowledge of risk factors for ED linked to IHD was assessed with an original survey. The presence of ED was assessed using an abridged version of the International Index of Erectile Function-5 questionnaire. Increase in leisure-time physical activity was estimated using a leaflet based on the Framingham questionnaire. In all, 189 participants were unable to name any modifiable ED risk factors, and only 31 patients knew all 6 of them. The most frequently mentioned ED risk factor was smoking, whereas the least frequently mentioned was sedentary lifestyle. Awareness of smoking as an ED risk factor was closely related to the patients' level of education, place of residence, smoking and underlying ED in the individual patient. The ability to classify diabetes as a risk factor for ED was significantly related to the patients' level of education, place of residence, and the prevalence of diabetes in the evaluated group of respondents. The same relations were observed regarding hyperlipidaemia. Awareness of the negative impact a sedentary lifestyle has on the erectile process was found to be closely related to the patients' age, as well as their level of education. The performed study demonstrates the poor knowledge of IHD patients about the modifiable risk factors for ED. The factor that patients are the least aware of is sedentary lifestyle, which, simultaneously, is the risk factor that most frequently affects the respondents.

Quantitative Assessment of Free Flap Viability with CEUS Using an Integrated Perfusion Software.

New treatment strategies in oncology and trauma surgery lead to an increasing demand for soft tissue reconstruction with free tissue transfer. In previous studies, CEUS was proven to detect early flap failure. The aim of this study was to detect and quantify vascular disturbances after free flap transplantation using a fast integrated perfusion software tool. From 2011 to 2013, 33 patients were examined by one experienced radiologist using CEUS after a bolus injection of 1-2.4 ml of SonoVue(®). Flap perfusion was analysed qualitatively regarding contrast defects or delayed wash-in. Additionally, an integrated semi-quantitative analysis using time-intensity curve analysis (TIC) was performed. TIC analysis of the transplant was conducted on a centimetre-by-centimetre basis up to a penetration depth of 4 cm. The 2 perfusion parameters "Time to PEAK" and "Area under the Curve" were compared in patients without complications vs. patients with minor complications or complete flap loss to figure out significant differences. TtoPk is given in seconds (s) and Area is given in relative units (rU) Results: A regular postoperative process was observed in 26 (79%) patients. In contrast, 5 (15%) patients with partial superficial flap necrosis, 1 patient (3%) with complete flap loss and 1 patient (3%) with haematoma were observed. TtoPk revealed no significant differences, whereas Area revealed significantly lower perfusion values in the corresponding areas in patients with complications. The critical threshold for sufficient flap perfusion was set below 150 rU. In conclusion, CEUS is a mobile and cost-effective opportunity to quantify tissue perfusion and can even be used almost without any restrictions in multi-morbid patients with renal and hepatic failure.

Reconstructive surgery and patients with spinal cord injury: Perioperative considerations for the plastic surgeon

Background: Patients with spinal cord injury (SCI) requiring reconstructive surgery, particularly for pressure ulcers, are ubiquitous in Plastic and Reconstructive Surgery practices. Much of the current literature focuses on operative techniques, antibiotic indications, sitting protocols, and dressing and bedding choices. Methods: This paper reviews normal neuroanatomy, outlines changes in neurophysiology observed in spinal cord injury, and addresses concepts related to perioperative care that are highly relevant but often under-emphasised. Results: Vascular disturbances such as autonomic dysreflexia and orthostatic hypotension are dangerous phenomena occurring in this patient population that, if not properly recognised and treated, may result in complications such as haematoma, flap loss, inadequate tissue perfusion, and death. The management of spasticity, deep venous thrombosis, and perioperative pain are also relevant and discussed in this paper. Conclusion: A basic understanding of these concepts is essential for the Plastic Surgeon involved in the care of patients with SCI and pressure ulcers, particularly before and after debridement or reconstruction.

Arthroscopic Treatment of Intraosseous Ganglion Cyst of the Lunate Bone

Intraosseous ganglion cysts are rare causes of wrist pain. Surgical treatment of this pathologic condition yields good results and a low recurrence rate. The main complications are joint stiffness and vascular disturbances of the lunate bone. Wrist arthroscopy is a surgical technique that reduces the intra-articular operative area and therefore minimizes postoperative stiffness. This article describes an arthroscopic technique used for lunate intraosseous cyst resection associated with an autologous bone graft in a series of cases to prevent joint stiffness while respecting the scapholunate ligament. This study was based on a series of 4 patients, all of whom had wrist pain because of intraosseous ganglion cysts. Arthrosynovial cyst resection, ganglion curettage, and bone grafting were performed arthroscopically. Pain had totally disappeared within 2 months after the operation in 100% of patients. The average hand grip strength was estimated at 100% compared with the opposite side, and articular ranges of motion were the same on both sides in 100% of cases. No complications were reported after surgery. On the basis of these results, arthroscopic treatment of intraosseous synovial ganglion cysts seems to be more efficient and helpful in overcoming the limitations of classic open surgery in terms of complications.

Pathogenesis of osteochondrosis dissecans: How does this translate to management of the clinical case?

SummaryOsteochondrosis (OC) is the most prevalent developmental orthopaedic disease in the horse. It is a complex disorder because of the interplay of factors that influence the formation of lesions and the ensuing natural healing process, the end result of which determines clinical outcome. The early pathogenetic mechanism ofOChas long remained elusive, but recent research has provided compelling evidence for vascular disturbances leading to areas of ischaemic necrosis in the subarticular growth cartilage as the primary event. The aetiological factors that influence the process of the development of lesions are many and comprise both genetic and environmental factors. The genetic background ofOC(dissecans) is highly complex with quantitative trait loci associated with some form ofOCfound on not fewer than 22 of the 33 chromosomes of the horse, and different manifestations and locations ofOChaving probably different genetic backgrounds. The environmental factors can be divided into nutritional factors and factors influencing the biomechanical loading of joints. Feeding large quantities of easily digestible carbohydrates is a clear risk factor and also the availability of sufficient copper for mares in the last part of pregnancy is important. Factors influencing the biomechanical loading of joints include the exercise regimen of foals, paddock size and roughness of terrain, and conformation. EquineOCis rarely a life‐threatening disease and the prognosis of (surgical) treatment is good to very good. However, the impact on economics of the equine industry and on horse welfare is large. This impact can only be lessened by the judicious management of both horse breeding and horse husbandry. Some of the measures that would alleviate the burden ofOCconflict with (commercial) pressures from the industry and a balance between human‐imposed breeding and performance goals and the interest of the animal itself should be sought.

Circulating CD34-positive cells, glomerular filtration rate and triglycerides in relation to hypertension

ObjectiveSerum triglycerides have been reported to be independently associated with the development of chronic kidney disease (CKD), which is known to play a role in vascular disturbance. On the other hand, circulating CD34-positve cells, including endothelial progenitor cells, are reported to contribute to vascular repair. However, no studies have reported on the correlation between triglycerides and the number of CD34-positive cells. Since hypertension is well known factor for vascular impairment, the degree of correlation between serum triglycerides and circulating CD34-positve cells should account for hypertension status. MethodsWe conducted a cross-sectional study of 274 elderly Japanese men aged ≥60years (range 60–79 years) undergoing general health checkups. ResultsMultiple linear regression analysis of non-hypertensive subjects adjusting for classical cardiovascular risk factors showed that although triglyceride levels (1SD increments; 64 mg/dL) did not significantly correlate with glomerular filtration rate (GFR) (β = −2.06, p = 0.163), a significant positive correlation was seen between triglycerides and the number of circulating CD34-positive cells (β = 0.50, p = 0.004). In hypertensive subjects, a significant inverse correlation between triglycerides and GFR was observed (β = −2.66, p = 0.035), whereas no significant correlation between triglycerides and the number of circulating CD34-positive cells was noted (β = −0.004, p = 0.974). ConclusionSince endothelial progenitor cells (CD34-positive cells) have been reported to contribute to vascular repair, our results indicate that in non-hypertensive subjects, triglycerides may stimulate an increase in circulating CD34-positive cells (vascular repair) by inducing vascular disturbance.

P33. Decreasing of placental progesterone induced blocking factor expression and spiral artery remodeling disturbance in mice preeclampsia model

Introduction Preeclampsia is a major cause of morbidity and mortality in our developing country. The biggest obstacle in the high prevalence of preeclampsia and its management is due to lack of knowledge in preeclampsia pathologic mechanism. Progesterone is an important pregnancy hormone that has immunomodulatory effect by inducing progesterone induced blocking factor (PIBF) release, due to binding of progesterone with its receptor in lymphocyte. PIBF inhibits cytolytic NK cells activity and inducing T-helper 2 cytokine dominant while on contrary, preeclampsia has a condition of T-helper 1 cytokine dominant and increase of NK cells cytolytic activity. This was the first study to evaluated PIBF expression directly on the placenta when the pathogenesis of preeclampsia occurred after completion of vascular remodeling in animal models. Objective The objectives of this study were to compare placental PIBF expression, spiral artery wall thickness as characteristic of vascular remodeling disturbance and investigated correlation between both in mice preeclampsia model. Methods This experimental study used 32 pregnant mus musculus mice and randomly divided to normal group and preeclampsia model group. Our preeclampsia model was created by injecting anti-Qa2 (anti HLA-G) 10 ng from 1st until 4th day of pregnancy, to reduced HLA-G expression. Termination of both groups were performed after completion of spiral artery remodeling in mice by day 16th of pregnancy followed by immunohistochemistry examination for PIBF expression using immunoreactive score and spiral artery wall thickness measurement. Ethical clearance was taken from Medical Veterinary Faculty ethics commission. Difference and correlation were analysed using SPSS 20. Probability values Result In the result, PIBF were expressed in trophoblast, decidual and lymphocyte cells in placental tissue. The placental PIBF expression on preeclampsia model (2.01 ± 1.14) was significantly reduced (p ± 0.01) compared with control (3.99 ± 2.53). There was a significant increase of spiral artery wall thickness (p ± 0.001) in preeclampsia model (20.70 ± 5.93 micrometers) compared with control (9.98 ± 3.36 micrometers). There was a significant association (p ± 0.001) with negative correlation (rho/Pearson correlation = −0.623) between placental PIBF expression and the spiral artery wall thickness. Conclusion We concluded a decreased expression of placental PIBF and the increase of spiral artery wall thickness as a characteristic of spiral artery remodeling disturbance in mice model of preeclampsia, with negative correlation between placental PIBF expression and spiral artery wall thickness.

Internal hernia after laparoscopic-assisted proximal gastrectomy with jejunal interposition for gastric cancer: a case report.

Internal hernia after gastrectomy is a rare complication. It can progress rapidly to vascular disturbance, necrosis, and perforation, therefore early diagnosis and surgical treatment is essential. We present a case of internal hernia following laparoscopic-assisted proximal gastrectomy with jejunal interposition reconstruction in a 68-year-old man, who presented with acute abdominal pain and vomiting. Computed tomography showed a whirl sign, ascites, and a closed-loop formation of the small intestine. We diagnosed an internal hernia and performed emergency surgery. Laparotomy revealed chyle-like ascites and extensive small intestine with poor color. We recognized that about 20 cm of jejunum from the ligament of Treitz was strangulated behind the pedicle of the jejunum lifted during laparoscopic-assisted proximal gastrectomy. We relieved the strangulation, whereupon the color of the strangulated intestine was restored. Therefore, we did not perform intestinal resection and reconstruction. Finally, we fixed the jejunal pedicle and mesentery of the transverse colon. We report this case as there are few reported cases of internal hernia after laparoscopic-assisted proximal gastrectomy.

Uterine artery dysfunction in pregnant ACE2 knockout mice is associated with placental hypoxia and reduced umbilical blood flow velocity.

Angiotensin-converting enzyme 2 (ACE2) knockout is associated with reduced fetal weight at late gestation; however, whether uteroplacental vascular and/or hemodynamic disturbances underlie this growth-restricted phenotype is unknown. Uterine artery reactivity and flow velocities, umbilical flow velocities, trophoblast invasion, and placental hypoxia were determined in ACE2 knockout (KO) and C57Bl/6 wild-type (WT) mice at day 14 of gestation. Although systolic blood pressure was higher in pregnant ACE2 KO vs. WT mice (102.3 ± 5.1 vs. 85.1 ± 1.9 mmHg, n = 5-6), the magnitude of difference was similar to that observed in nonpregnant ACE2 KO vs. WT mice. Maternal urinary protein excretion, serum creatinine, and kidney or heart weights were not different in ACE2 KO vs. WT. Fetal weight and pup-to-placental weight ratio were lower in ACE2 KO vs. WT mice. A higher sensitivity to Ang II [pD2 8.64 ± 0.04 vs. 8.5 ± 0.03 (-log EC50)] and greater maximal contraction to phenylephrine (169.0 ± 9.0 vs. 139.0 ± 7.0% KMAX), were associated with lower immunostaining for Ang II receptor 2 and fibrinoid content of the uterine artery in ACE2 KO mice. Uterine artery flow velocities and trophoblast invasion were similar between study groups. In contrast, umbilical artery peak systolic velocities (60.2 ± 4.5 vs. 75.1 ± 4.5 mm/s) and the resistance index measured using VEVO 2100 ultrasound were lower in the ACE2 KO vs. WT mice. Immunostaining for pimonidazole, a marker of hypoxia, and hypoxia-inducible factor-2α were higher in the trophospongium and placental labyrinth of the ACE2 KO vs. WT. In summary, placental hypoxia and uterine artery dysfunction develop before major growth of the fetus occurs and may explain the fetal growth restricted phenotype.