Acute Blockage Research Articles

Proteomic Analysis of Aqueous Humor in Central Retinal Artery Occlusion: Unveiling Novel Insights Into Disease Pathophysiology.

Central retinal artery occlusion (CRAO) is an ocular emergency that results from acute blockage of the blood supply to the retina and leads to a sudden vision loss. Other forms of ischemic retinopathies include diabetic retinopathy (DR), which involves chronic retinal ischemia and remains the leading cause of blindness in working-age adults. This study is the first to conduct a proteomic analysis of aqueous humor (AH) from patients with CRAO with a comparative analysis using vitreous humor (VH) samples from patients with DR. AH samples were collected from 10 patients with CRAO undergoing paracentesis and 10 controls undergoing cataract surgery. VH samples were collected from 10 patients with DR and 10 non-diabetic controls undergoing pars plana vitrectomy (PPV). Samples were analyzed using mass spectrometry. Compared with controls, AH levels of 36 differentially expressed proteins (DEPs) were identified in patients with CRAO. Qiagen Ingenuity Pathway Analysis (IPA) revealed 11 proteins linked to ophthalmic diseases. Notably, enolase 2, a glycolysis enzyme isoform primarily expressed in neurons, was upregulated, suggesting neuronal injury and enzyme release. Additionally, clusterin, a protective glycoprotein, was downregulated. ELISA was conducted to confirm proteomics data. VH samples from patients with DR exhibited changes in a distinct set of proteins, including ones previously reported in the literature. The study provides novel insights into CRAO pathophysiology with multiple hits identified. Proteomic results differed between DR and CRAO studies, likely due to the different pathophysiology and disease duration. This is the first proteomic analysis of CRAO AH, with the potential to identify future therapeutic targets.

Removal of a benign tumor in the knee by a combined approach in a patient with acute blockage of the joint: Case report

Soft tissue tumors are the most prevalent tumor lesions in the extremities, of which lipomas are the most frequent tumors in soft tissue, highlighting that these are benign conditions, despite being tumors, however, intra-articular cases are extremely rare, which contrasts with arborescent lipomas that are well described in the literature, which are secondary to degenerative processes in the knee and not neoplastic lesions. Intra-articular lipomas are rare, with the most common location being the knee, followed by the hip, lumbar spine, elbow, shoulder and wrist. Within the lipomas of the knee we find the arborescent lipoma, this is the product of degenerative changes established in the joint, which will be compromised and will give a manifest clinical appearance depending on its extension and size, which in turn will allow us to determine adequate management. surgical, in this case report we present a resection performed through arthroscopy and open approach due to a large lesion that generated joint blockage which subsides after the intervention.

Premenopausal and postmenopausal women presenting with acute coronary syndrome: A comparison study of their clinical and angiographic profiles

ABSTRACT Context: Acute coronary syndrome (ACS) encompasses a range of conditions associated with sudden, reduced blood flow to the heart, typically due to an acute blockage of a coronary artery. The severity and specific location of the blockage determine the type of ACS and its consequences. Menopause, marked by a significant decline in estrogen levels, is known to negatively impact circulatory function and metabolism, potentially increasing the risk of ACS. However, there is a lack of studies comparing the burden of cardiovascular disease between pre- and postmenopausal women. Aim: This study seeks to bridge the knowledge gap regarding the impact of menopausal status on the presentation and severity of ACS in women. Setting and Design: This retrospective observational study was conducted in a single center, India, over 7 months. Materials and Methods: The study included 250 patient populations among which 120 were premenopausal and 130 were postmenopausal women. The subjects were evaluated for their clinical and angiographic profile. Statistical Analysis Used: Differences between pre- and postmenopausal women were compared using the two-sample t-test for continuous variables and the Chi-square test for categorical variables. Results: In this study, the mean ± standard deviation number of stenotic vessels and Gensini score was significantly higher in postmenopausal patients (2.46 ± 0.74 and 47.35 ± 20.92, respectively) than in premenopausal patients (1.30 ± 0.27 and 13.13 ± 4.43, respectively) which indicate the severity of coronary artery disease in postmenopausal women. Conclusion: Menopausal status significantly impacts the severity of coronary artery disease (CAD) in women presenting with ACS, as demonstrated by the marked difference in Gensini scores.

Acute Occlusion of a “Protected” Left Main Coronary Artery Manifesting as an Acute Coronary Syndrome with Heart Failure: How much Protected it is?

Despite the progress made in technological advancements, the utilization of stenting for both protected and unprotected left main coronary artery (LMCA) disease remains associated with elevated rates of long-term mortality and significant adverse clinical events, sometimes manifesting as cardiogenic shock. A considerable number of individuals retain the opportunity to receive catheter-based interventional therapy as a viable substitute for re-operative coronary artery bypass grafting (CABG). Despite the changed appearance, patients with acute blockage of the protected LMCA still have major adverse cardiac events (MACE) at a similar rate. Acute occlusion of the unprotected LMCA as an acute coronary syndrome (ACS) is uncommon, but that of the protected LMCA is relatively rare. We present a case of a post-CABG patient who developed ACS as a posterior wall myocardial infarction and acute left ventricular failure due to obstruction of a protected LMCA with substantial stenosis across its distal segment extending to the left circumflex (LCx) artery. The pharmaco-invasive management of the protected LMCA thrombotic occlusion with primary percutaneous coronary intervention resulted in significant patient improvement. These lesions are amenable to complex and high-risk coronary intervention with current technology, and the results have been quite encouraging in terms of long-term survival.

Blockage of STAT3 during epileptogenesis prevents GABAergic loss and imprinting of the epileptic state.

Epilepsy, characterized by recurrent unprovoked seizures resulting from a wide variety of causes, is one of the world's most prominent neurological disabilities. Seizures, which are an expression of neuronal network dysfunction, occur in a positive feedback loop of concomitant factors, including neuro-inflammatory responses, where seizures generate more seizures. Among other pathways involved in inflammatory responses, the JAK/STAT signalling pathway has been proposed to participate in epilepsy. Here, we tested an in vitro model of temporal lobe epilepsy, with the hypothesis that acute blockage of STAT3-phosphorylation during epileptogenesis would prevent structural damage in the hippocampal circuitry and the imprinting of both neural epileptic activity and inflammatory glial states. We performed calcium imaging of spontaneous circuit dynamics in organotypic hippocampal slices previously exposed to epileptogenic conditions through the blockage of GABAergic synaptic transmission. Epileptogenic conditions lead to epileptic dynamics imprinted on circuits in terms of increased neuronal firing and circuit synchronization, increased correlated activity in neuronal pairs and decreased complexity in synchronization patterns. Acute blockage of the STAT3-phosphorylation during epileptogenesis prevented the imprinting of epileptic activity patterns, general cell loss, loss of GABAergic neurons and the persistence of reactive glial states. This work provides mechanistic evidence that blocking the STAT3 signalling pathway during epileptogenesis can prevent patho-topological persistent reorganization of neuro-glial circuits.

Role Plays Interventional Approach towards Mothers of Toddlers Regarding Prevention of Choking and Pulmonary Aspiration

Background: Toddlers are exposed to a variety of risk factors which includes playing with small material like coins, marbles, rings, unsupervised play and eating, children with decreased consciousness which may leads to choking. Children's respiratory crises and cardiac arrest are frequently brought on by choking or the introduction of an outside object into the airway, especially in children within the 6 months and 3 years of age. Childhood injuries have recently been a public health concern due to the frequency of pulmonary aspiration and choking in children under two years old, as well as mother referrals to medical institutions. According to research conducted in the United States, choking on external items caused 2.9% of children under the age of 4 is prone to die.Aim and Objective: To assess effectiveness of role play regarding prevention of choking and pulmonary aspiration among the mothers of toddler and associate findings with demographic variables.Material and methods: This research were adopted a pre-post experimental research approach among mothers of toddler between the age group of 20-40. 135 mothers of toddler involved in this research. Data were analyzed using the IBM Corp. Released 2016. IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp. Qualitative variables were described as numbers and percentages.Results: Before intervention minimum knowledge score was 6.54 and maximum knowledge score percentage was 27.25%. After intervention maximum knowledge score was 70.12%. the average knowledge score has increased by 10.28 and currently represents 42.97% of the total possible points.Conclusion: Choking is a medical condition in which acute blockage of upper respiratory tract occur by a solid particle such as coins, lollypop, hairclips, grapes, marbles, foreign objects accidentally which leads to respiratory crisis like asphyxia as well as cardiac arrest. Toddlers and elderly age group are prone for choking and pulmonary aspiration, and it occur when the unsupervised play and eating, children with decreased consciousness which may leads to choking. It is incorrect to refer to any circumstances in which an obstruction of the airways causes a people to die as a result of choking. The word "choking" excludes deaths caused by diseases other than those caused by strangling, drowning, and gagging, which are all distinct medical conditions. Thus, the prevention of choking and pulmonary aspiration can be done by increasing knowledge and awareness about common sign and symptoms which includes gagging, watery eyes, reddening of face, coughing as well as teaching about preventive measures are choking technique which includes back blow and abdominal thrust and Heimlich maneuver among the mothers of toddler. In this study, the effectiveness of role play regarding prevention of choking and pulmonary aspiration among the mothers of toddler is improved from 26.96% to 70.12%.

Acute and long-term success of left atrial anterior line and mitral isthmus line ablation in patients after mitral valve surgery.

Perimitral flutter and atrial fibrillation may occur in patients with prior surgical mitral valve (MV) repair or replacement and can be challenging for percutaneous catheter ablation. This study sought to determine the feasibility, acute success and durability of catheter ablation of atrial fibrillation or atrial tachycardia by way of a mitral isthmus line (MIL) or an anterior line (AL). A total of 81 patients (49 males, mean age 62±11 years) with prior MV replacement (n=30) or reconstruction (n=51) underwent creation of a MIL (34) and/or an AL (72). Acute bidirectional block of the MIL was successfully achieved in 24/34 cases and of the AL in 64/72 patients. Patients of the control group without prior MV surgery were matched 1:1 with the valve group. In the AL control subgroup, acute bidirectional block was achieved in 65/72 patients. Acute blockage in the MIL control subgroup could be achieved in 31/34 patients. The MIL valve subgroup showed the worst results in terms of durability, whereas a similar trend emerged in the control group and the AL valve subgroup (probability of failure in MIL valve subgroup 2.224vs. MIL control subgroup 0.605 [Hazard Ratio (HR)=0.27, 95% confidence interval (CI), 0.11-0.65), P=.004]; probability of failure in AL valve subgroup 0.844vs. AL control subgroup 1.03 [HR=1.22 (95% CI, 0.66-2.26), P=.523]). Percutaneous creation of MIL and AL is feasible and safe in patients with prior MV replacement/repair and associated with moderate acute and long-term success rates to achieve bidirectional block.

Unsupervised domain adaptive myocardial infarction MRI classification diagnostics model based on target domain confused sample resampling

ObjectiveInefficient circulatory system due to blockage of blood vessels leads to myocardial infarction and acute blockage. Myocardial infarction is frequently classified and diagnosed in medical treatment using MRI, yet this method is ineffective and prone to error. As a result, there are several implementation scenarios and clinical significance for employing deep learning to develop computer-aided algorithms to aid cardiologists in the routine examination of cardiac MRI. MethodsThis research uses two distinct domain classifiers to address this issue and achieve domain adaptation between the particular field and the specific part is a problem Current research on environment adaptive systems cannot effectively obtain and apply classification information for unsupervised scenes of target domain images. Insufficient information interchange between specific domains and specific domains is a problem. In this study, two different domain classifiers are used to solve this problem and achieve domain adaption. To effectively mine the source domain images for classification understanding, an unsupervised MRI classification technique for myocardial infarction called CardiacCN is proposed, which relies on adversarial instructions related to the interpolation of confusion specimens in the target domain for the conflict of confusion specimens for the target domain classification task. ResultsThe experimental results demonstrate that the CardiacCN model in this study performs better on the six domain adaption tasks of the Sunnybrook Cardiac Dataset (SCD) dataset and increases the mean target area myocardial infarction MRI classification accuracy by approximately 1.2 percent. The classification performance of the CardiacCN model on the target domain does not vary noticeably when the temperature-controlled duration hyper-parameter rl falls in the region of 5–30. According to the experimental findings, the CardiacCN model is more resistant to the excitable rl. The CardiacCN model suggested in this research may successfully increase the accuracy of the source domain predictor for the target domain myocardial infarction clinical scanning classification in unsupervised learning, as shown by the visualization analysis infrastructure provision nurture. It is evident from the visualization assessment of embedded features that the CardiacCN model may significantly increase the source domain classifier's accuracy for the target domain's classification of myocardial infarction in clinical scans under unsupervised conditions. ConclusionTo address misleading specimens with the inconsistent classification of target-domain myocardial infarction medical scans, this paper introduces the CardiacCN unsupervised domain adaptive MRI classification model, which relies on adversarial learning associated with resampling target-domain confusion samples. With this technique, implicit image classification information from the target domain is fully utilized, knowledge transfer from the target domain to the specific domain is encouraged, and the classification effect of the myocardial ischemia medical scan is improved in the target domain of the unsupervised scene.

Computational attributes of protein kinase-C gamma C2-domain & virtual screening for small molecules: elucidation from meta-dynamics simulations & free-energy calculations

Epilepsy, a moderate to chronic neuropathological condition, is induced by the acute blockage of synaptic and voltage-gated inhibitory conduction or through the activation of synaptic and voltage-gated excitatory conduction. The regulation of long-term potentiation (LTP) is important in the regulation of epileptic events, and its activity is linked to specific protein kinases. The PKC-γ subtype is a vaguely explored therapeutic target for neurological disorders, but in selected studies, it is proven to be a critical intermediate protein in LTP. This study utilized computational modelling approaches including receptor-based docking, QSAR followed by explicit binding score assessment method MM/GBSA, MM/PBSA (EDA) and MTD simulation-based FES iteration. This was performed to virtually screen the small molecule libraries, which comprised about 2.79 lacs compounds against the Ca2+-binding site of the PKC-γ-C2 regulatory domain. The screened molecules LIG-41 ([4-Oxo-4-(4-phenylmethoxyanilino) butyl] azanium) and LIG-16 (Emixustat) exhibit overall optimal attributes in the above-mentioned parameters. The two leads are expected to inhibit the Ca2+-mediated PKC-γ activity. Communicated by Ramaswamy H. Sarma

Targeted activation of midbrain neurons restores locomotor function in mouse models of parkinsonism

The pedunculopontine nucleus (PPN) is a locomotor command area containing glutamatergic neurons that control locomotor initiation and maintenance. These motor actions are deficient in Parkinson’s disease (PD), where dopaminergic neurodegeneration alters basal ganglia activity. Being downstream of the basal ganglia, the PPN may be a suitable target for ameliorating parkinsonian motor symptoms. Here, we use in vivo cell-type specific PPN activation to restore motor function in two mouse models of parkinsonism made by acute pharmacological blockage of dopamine transmission. With a combination of chemo- and opto-genetics, we show that excitation of caudal glutamatergic PPN neurons can normalize the otherwise severe locomotor deficit in PD, whereas targeting the local GABAergic population only leads to recovery of slow locomotion. The motor rescue driven by glutamatergic PPN activation is independent of activity in nearby locomotor promoting glutamatergic Cuneiform neurons. Our observations point to caudal glutamatergic PPN neurons as a potential target for neuromodulatory restoration of locomotor function in PD.

The Positive Report Of benson Relaxation For Acute Miocard Infark Pain: A Case Report Study

Structured Acute Myocardial Infarction (AMI) is myocardial necrosis caused by inadequate blood supply due to acute blockage of the coronary arteries. Typical signs and symptoms experienced in AMI patients are chest pain such as squeezing, pressing, stabbing, heat or being crushed by heavy objects. Giving pharmacological therapy such as oxygen, nitroglycerin and aspirin can reduce AMI pain, but if the effects of the drug begin to decrease the pain will back, so complementary therapy is needed to help reduce pain in AMI patients. The purpose of the research is to evaluate Benson's relaxation effect in reducing chest pain in acute myocardial infarction (AMI). The descriptive method was used by involving 2 subjects who experience chest pain. The intervention was carried out once a day for 2 days with an intervention duration of 30 minutes. The results of the evaluation were obtained, there was a decrease in both patients from 5 scales to 2 scales in patient 1 and 1 scale in patient 2. The combination of both pharmacological therapy and Benson relaxation can reduce the scale of pain. Benson relaxation can be used as a complementary therapy in reducing pain in AMI patients.

Histochemical characteristics of nitrergic neuronal system during acute alcohol intoxication and nNOS blockage in the rat lateral septum

Annotation. Alcohol is a one of the most frequently consumed substances of abuse, which can cause addiction or alcohol use disorders (AUDs). Alcohol addiction leads to decrease of the life quality of patients and considerable economic burden. Neuronal mechanisms of addiction are intensively studied. One of the most important systems involved in this process is a brain reward system that includes lateral septum (LS). Additionally alcohol consumption changes activity of the neurotransmitter systems including the nitric oxide (NO). Recent studies for blockage of nitric oxide synthase (NOS) for cocaine addiction and late stages of AUDs demonstrated that a group of the substances known as blockers of NOS can be referred to as candidates for alcohol addiction therapy. The aim of our research was to investigate histochemical characteristics of NO-system in LS, its response to acute alcohol intoxication including or excluding neuronal NOS (nNOS) blockage with selective inhibitor – 7-nitroindazole (7-NI). This study involved three experimental groups of animals (control group (n=4), group with acute alcohol intoxication (n=4), group of nNOS blockage with acute alcohol intoxication (n=4)). For statistical analysis, one-way Kruskal-Wallis test was implemented to reveal differences between groups (Matlab, Mathworks). We have identified NOS-positive structures in LS consisting of big neurons, medium/small neurons and nerve fibers. Acute alcohol intoxication activated subpopulations of NOS-positive medium/small neurons and nerve fibers. Moreover, we determined that ethanol-induced changes can be blocked with selective nNOS inhibitor 7-NI.

A CROSS-SECTIONAL STUDY OF STANDARD INTERVENTION OF INTESTINAL OBSTRUCTION IN A TERTIARY HOSPITAL IN CENTRAL INDIA.

Background: A common surgical emergency, intestinal blockage has a high death and morbidity rate. Intestinal blockage accounts for about 15% of all emergency room visits for acute abdominal discomfort. Acute intestinal obstruction can take several forms, ranging from a seemingly normal look with just minor stomach pain and distension to a situation of hypovolemic or septic shock (or both) requiring an emergency treatment.
 Aim: The goal of this study was to see how our tertiary hospital managed intestinal obstruction operations.
 Material and Methods: Patients in the current study ranged in age from 21 to 80 and had a surgically treated acute intestinal blockage. Patients with severe signs and symptoms of acute blockage were treated with an appropriate surgical approach after initial resuscitation. All of the data was entered into a spreadsheet and analysed with descriptive statistics.
 Results: During the study period, 288 patients received surgery for acute intestinal blockage. The most prevalent age group (26 percent) was 51 to 60 years old, followed by 41 to 50 years old (21 percent ). Male patients were 2.8 times more likely than female patients to be afflicted. Previous abdominal surgery (56 percent), diabetes (31%), smoking (25%), hypertension (24%), and bronchial asthma/ COPD (15%) were all discovered to be common co-morbidities in this study. The most common causes of intestinal obstruction in this study were postoperative adhesions (47 percent), malignancy (15 percent), obstructed hernia (11 percent), and Koch's abdomen (8 percent ). The most prevalent surgical procedures in this study were adhesion removal (47 percent), resection and anastomosis (22 percent), diversion colostomy (13 percent), and hernioplasty (13 percent) (11 percent ). Fever (15%) and wound infection (11%) were the most prevalent post-operative problems, respectively. The rate of post-operative death was 13%. There are nine patients in all. The majority of deaths are caused by complications such as septicemia, peritonitis, and lung infection.
 Conclusion: Postoperative adhesions are a common cause of intestinal blockage. Early surgical techniques, when combined with clinical diagnosis and radiological data, may improve the outcome of acute intestinal obstruction.
 Keywords: surgical management, acute intestinal obstruction, adhesions, adhesiolysis.

Branch retinal artery occlusion secondary to high-altitude exposure and diabetic retinopathy: a case report

BackgroundTo report a case of branch retinal artery occlusion (BRAO) secondary to high-altitude exposure and diabetic retinopathy (DR), and to characterize the retinal changes before and after hyperbaric oxygen (HBO) treatment.Case presentationWe present a case of a 42-year-old man with DR who travelled to Tibet (in China, 3800 m/12467 ft. above mean sea level). The day after the end of his journey, the patient presented with acute, painless visual loss and visual field loss in his left eye. He was then diagnosed with BRAO, which is an acute blockage of blood flow. After HBO treatment, visual acuity and visual field were improved.ConclusionsHigh-altitude exposure and DR may be considered as relevant risk factors for BRAO. The ophthalmologist should be aware that the BRAO might be a rare presenting sign of high-altitude retinopathy (HAR), particularly in patients with DR. HBO treatment can be considered as a choice for ophthalmologists on treatment against BRAO.

Effects of In Vivo Administration of an Endothelial KCa Channel Activator on Recovery of Cardiac Function Following Acute Myocardial Infarction in Mice

Cessation of coronary blood flow, due to stenosis or acute blockage, produces prolonged ischemia that results in myocardial infarction (MI) and impaired cardiac function and blood pumping activity of heart. Increasing coronary blood flow to the ischemic area and/or reducing myocardial work are predicted to mitigate the damage typically associated with an acute MI injury. Recent studies from our group have demonstrated that pharmacological enhancement of endothelial KCa2.3 and KCa3.1 channels by the activator SKA‐31 improves agonist‐evoked vasodilation in small resistance arteries from multiple vascular beds and species. The goal of our present study is to investigate the potential cardio‐protective effects of SKA‐31 administration in male mice (12–15 weeks of age, C57B1/6 strain) following an acute myocardial infarct (MI) induced by permanent surgical ligation of the left‐anterior descending (LAD) coronary artery. Within 48 h post‐surgery, MI and sham surgery mice were treated orally with either vehicle or 10 mg/kg of SKA‐31 for 6–7 weeks. Myocardial damage in MI mice was confirmed by histological staining. Echocardiographic assessment of cardiac structure and function 2 weeks post‐surgery revealed that left ventricular (LV) wall thickness during systole and diastole was similar in sham animals treated with either vehicle or SKA‐31. In contrast, LV wall thickness during systole and diastole was ~30% greater in MI surgery mice receiving SKA‐31 treatment. At 4 weeks post‐surgery, sham animals exhibited LV wall thickness values during systole (1.00 mm ± 0.03, n=3) and diastole (0.82 mm ± 0.10, n=3) that were similar to those observed at 2 weeks, indicating that SKA‐31 treatment did not adversely affect these parameters. In MI surgery animals receiving SKA‐31 administration for 4 weeks, LV wall thickness during systole (0.97 mm ± 0.10, n=5) and diastole (0.80 mm ± 0.08, n =5) decreased to the values observed in sham surgery mice. At the end of the SKA‐31 treatment period, cardiac output (CO) and LV ejection fraction (EF) measured by pressure‐volume loop analysis were both higher in sham mice (CO = 6.49 mL/min, EF = 50.9%) compared with MI surgery animals (CO = 5.83 mL/min, EF = 40.7%). Following completion of ongoing measurements and analyses, we will present additional data describing changes in cardiac function in MI surgery mice treated with drug vehicle, and histological assessment of myocardial integrity in sham and MI surgery mice. Our preliminary findings thus far suggest that enhancement of endothelial KCa channel activity by SKA‐31 administration improves recovery of cardiac function following ischemic damage associated with blockade of the LAD coronary artery.Support or Funding InformationThis work was supported by research funding to APB from the Canadian Institutes of Health Research (MOP 142467) and the Natural Sciences and Engineering Research Council of Canada (RGPIN‐2017‐04116).

Abstract PD8-10: Regulation of breast tumor metastasis by the dynamic interaction between the TMEM doorway macrophage, tumor and endothelial cells

Abstract Tumor cell intravasation is an essential step in the metastatic cascade, but its exact mechanism is not completely understood. We have previously shown that the direct physical association of a tumor cell over-expressing Mena, a Tie2hi/Vegfhi macrophage and an endothelial cell, creates a micro-anatomic doorway called “tumor microenvironment of metastasis” (TMEM). TMEM are responsible for cancer cell intravasation and dissemination to distant sites. The density of TMEM doorways is a clinically validated prognostic marker of distant metastasis in breast cancer patients. Although we know that TMEM doorways create increased localized vascular permeability which cancer cells utilize to intravasate, the precise molecular mechanisms relating TMEM-doorway function and intravasation has not been elucidated. Active TMEM doorways are found in pre-invasive and invasive ductal breast carcinoma as well as in metastatic foci in lymph nodes and lungs, indicating that TMEM-mediated cancer cell dissemination occurs not only at the primary tumor site but also at metastatic sites, which may perpetuate metastatic dissemination even after removal of the primary tumor. Thus it is essential to understand the exact molecular mechanism of TMEM-doorway function so that specific targeted therapies can be developed to intercept systemic cancer cell dissemination. We outline here the exact molecular mechanism of TMEM-doorway functions. TMEM doorway endothelial cell-secreted Ang2 (a Tie2 ligand) stimulates VEGF expression and production by the Tie2hi TMEM macrophage. Subsequently, the TMEM doorway tumor cell- secreted CSF1 stimulates local secretion of VEGF from the Tie2hi TMEM macrophages, leading to dissociation of endothelial adherens and tight junctions near TMEM and cancer cell intravasation. In addition, we show that acute blockage of CSF1R and Tie2-Ang2 signaling by inhibitors and blocking antibodies both in vitro and in mammary tumors leads to decreased macrophage VEGF production and secretion, decreased tumor cell trans-endothelial migration, and decreased TMEM-dependent vascular permeability, tumor cell dissemination and circulating tumor cells. This is the first description of the molecular mechanisms regulating TMEM doorway function and thus represents a major step in defining new biomarkers and targets for the treatment of metastatic tumors. Citation Format: Chinmay Surve, Allison S. Harney, Mary Chen, Yarong Wang, Xianjun Ye, Yu Lin, Ved Sharma, Richard Stanley, Maja H. Oktay, John S. Condeelis. Regulation of breast tumor metastasis by the dynamic interaction between the TMEM doorway macrophage, tumor and endothelial cells [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD8-10.

Endoscopic Supernumerary Canine Tooth Extraction in an Adult Presented with Acute Nasal Blockage : A Case Report

Intranasal ectopic tooth, which can be derived from either supernumerary, deciduous or permanent tooth, is generally a rare event. Their existence can cause a wide array of complication such as epistaxis, nasal blockage, nasal pain, rhinosinusitis, septal deviation, septal abscess as well as oronasal fistula. We highlight a case of a canine supernumerary tooth that erupted at floor of nasal cavity, causing an acute unilateral nasal blockage, and managed successfully with an endoscopic nasal tooth extraction.International Journal of Human and Health Sciences Vol. 03 No. 04 October’19 Page : 235-237

Abstract 976: Regulation of breast tumor metastasis by the dynamic interaction between the TMEM macrophage, tumor, and endothelial cells

Abstract Tumor cell intravasation is an essential step in the metastatic cascade, but its exact mechanism is not completely understood. We have previously shown that the direct physical association of a tumor cell over-expressing Mena, a perivascular Tie2hi/Vegfhi macrophage and an endothelial cell, forming a cell triad termed “tumor microenvironment of metastasis” (TMEM), increases vascular permeability, facilitating intravasation of tumor cells. It is only at the TMEM site that intravasation occurs leading to breast tumor metastasis. TMEM density is a clinically validated prognostic marker of distant metastasis in breast cancer patients. The precise molecular mechanisms relating TMEM function had not been elucidated. Here we describe the molecular mechanism. We show here that TMEM function involves the three cells in TMEM: firstly endothelial cell-secreted Ang2 stimulates VEGF build up in the TMEM macrophage, secondly a tumor cell secretes CSF1 which, third, stimulates the TMEM macrophage VEGF secretion, leading to vascular opening and metastasis. In addition, we show that acute blockage of CSF1R and Tie2-Ang2 signaling by inhibitors and blocking antibodies both in vitro and in mammary tumors leads to decreased macrophage VEGF production and secretion, decreased trans-endothelial migration of tumor cells, and decreased TMEM-dependent vascular permeability, circulating tumor cells and lung metastases. We conclude that dynamic interaction between the cells associated with TMEM leads to Ang2 and CSF1-mediated stimulation of macrophage VEGF expression and secretion leading to vascular opening, resulting in tumor cell intravasation. This is the first description of the molecular mechanism behind the predictive power of the clinically used prognostic marker TMEM and represents a major step in defining new biomarkers and targets for the treatment of metastatic tumors. Citation Format: Chinmay R. Surve, Allison Harney, Yarong Wang, Xiaoming Chen, Ved Sharma, Richard Stanley, Maja Oktay, John Condeelis. Regulation of breast tumor metastasis by the dynamic interaction between the TMEM macrophage, tumor, and endothelial cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 976.

Laser Pan-Retinal Photocoagulation to Treat Central Retinal Vein Occlusion

Introduction. Retinal Vein Occlusion (RVO) is the second most common retinal blood vessel disease after diabetic retinopathy. CRVO is an acute blockage of the central retinal vein that causes abnormalities in the retina, characterized by sudden decreased vision. Based on the potential for vision loss from this retinal disease, proper diagnosis and management is needed to prevent further complications.
 Case Presentation. A man, age 50 years old, a civil servant, came to the eye clinic of Mohammad Hosein Hospital on February 2017. The main complaint was vision of right eye suddenly blurred since 5 months before. Based on the above examination found decreased vision in one eye, with visual acuity better than 6/60 and no RAPD. The funduscopic examination above shows the presence of dilatation and tortousity in the central retinal vein, dot / blot bleeding and flame shaped hemorrhages in all quadrants, exudates, neovascularization of the retina and optic disk, and the presence of edema in the optic disc and macula.
 Conclusion. Management performed on these patients is by performing a Pan-Retinal Photocoagulation (PRP) laser and Grid-Pattern Photocoagulation. The selection of this therapy is based on the consideration that the patient has been suffering from CRVO for more than 3 months.

TRPV1 Exaggerates Cardiovascular Responses to Physical Exercise in Normotensive but Not in Hypertensive Rats

IntroductionThe transient receptor potential vanilloid‐1 (TRPV1) is an ion channel involved in several physiological responses, including arterial pressure regulation. This channel seems to have an important role in endothelium‐dependent and ‐independent vasodilation. In spontaneously hypertensive rats (SHRs), chronic treatment with a TRPV1 agonist decreases mean arterial pressure, which makes the TRPV1 a potential target for hypertension treatment. We have already shown that in normotensive rats, the acute blockage of TRPV1 channels leads to an exaggerated increase in mean arterial pressure and heart rate during physical exercise. Therefore, in this study we investigated whether the role of TRPV1 channels in cardiovascular responses during physical exercise is affected by arterial hypertension.MethodsMale Wistar normotensive and Wistar‐Kyoto SHRs (16–19 wk) were implanted with an intra‐arterial (ascending aorta) catheter to measure arterial pressure. The rats received an intra‐arterial injection of a TRPV1 antagonist N‐(4‐[6‐(4‐trifluoromethyl‐phenyl)‐pyrimidin‐4‐yloxy]‐benzothiazol‐2‐yl)‐acetamide (AMG 517, 60 μg/kg) or vehicle (20% ethanol in saline) and then were subjected to an incremental‐speed treadmill running at 24°C until fatigue. The pulsatile arterial pressure (which allowed the determination of mean, systolic and diastolic arterial pressures and the heart rate) was measured throughout the exercise period.ResultsIn both normotensive rats and SHR, the incremental exercise increased mean, systolic and diastolic arterial pressures and the heart rate (for mean arterial pressure, fatigue: Normotensive: 126 ± 3 mmHg; SHR: 165 ± 4 mmHg versus beginning of exercise: Normotensive: 108 ± 4 mmHg; SHR: 158 ± 5 mmHg). As expected, in the normotensive rats, the AMG 517 led to a greater exercise‐induced increases in the mean, systolic and diastolic arterial pressures and in the heart rate. In contrast, the TRPV1 antagonist had no effect on any of the cardiovascular variables evaluated in the SHRs (for mean arterial pressure, min 19: AMG 517: 161 ± 5 mmHg; Vehicle 164 ± 4 mmHg). The changes (values at fatigue minus values at the beginning of exercise) in the mean arterial pressure (Normotensive: 20.1 ± 1.8 mmHg versus SHR 10.5 ± 3.3 mmHg; p < 0.05) as well as in the heart rate (Normotensive: 196 ± 13 bpm versus SHR: 149 ± 9 bpm, p < 0.05) were greater in normotensive rats than in SHRs when the incremental exercise was performed after the TRPV1 antagonist injection.ConclusionsDespite inducing marked alterations in blood pressure regulation in the normotensive rats, the TRPV1 antagonist injection did not modify the cardiovascular responses to exercise in the SHRs, which suggests that the arterial hypertension affects the TRPV1‐mediated mechanism involved in arterial pressure regulation during exercise.Support or Funding InformationCAPES, CNPq and FAPEMIG.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.