Acute Inflammatory Edema Research Articles

Reduction of Edema and Pain in Transcutaneous Electrical Nerve Stimulation Treated-Arthritic Rat.

Transcutaneous electrical nerve stimulation (TENS) has been used to reduce pain or improve motor function in musculoskeletal and neurological disorders in the clinic. Although some studies have suggested electrotherapy as an intervention for edema, the effects and mechanisms of TENS on inflammation-induced edema remain unclear. Thus, we aimed to investigate the effects of TENS on arthritic pain with edema. 1% carrageenan was injected into the right tibiofemoral joint of 69 male Sprague-Dawley rats (200-250 g). After the development of arthritic pain, low-frequency (4-Hz, Low-TENS, n = 25) and high-frequency (100-Hz, High-TENS, n = 25) TENS with sub-motor threshold or placebo-TENS (n = 19) was applied for 20-min to medio-lateral part of the ipsilateral side. Weight bearing and knee-bend tests were used to assess pain-like behaviors. Also, we examined the size of edema and measured tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) levels in the synovium by western blot. Eight rats in each of the two TENS groups were injected with Naloxone. Edema was reduced in the low- and high-frequency TENS groups at 6-h. TENS-treated rats showed reduced pain in the knee-bend test at 6-h. We observed decreased weight load shifts on the ipsilateral side in TENS groups. Naloxone reduced these effects. TNF-α and IL-1β expression decreased in the synovial membrane at 6-h. These results suggest that low- and high-frequency TENS have acutely positive effects on inflammatory edema, with the management of arthritic pain and reduction in pro-inflammatory mediators. Therefore, Low-TENS and High-TENS may be useful in treating acute inflammatory pain and edema.

Study of the Anti-inflammatory Activity of 2-hydroxy-4-oxo-4-R-2-butenoates of Heterylammonium, which Have an Effect on the Blood Clotting System

Introduction. The use of anticoagulants is relevant in therapeutic, cardiological, neurological practice, geriatrics, obstetrics and gynecology, as well as in complications associated with COVID-19 infection and vaccination. In-depth studies of additional pleiotropic effects of existing anticoagulants are being conducted. The anti-inflammatory effect of heparins and direct oral anticoagulants was found. Special emphasis is placed on the existing close relationship between coagulation and inflammatory processes. The interaction of anticoagulants with nonsteroidal anti-inflammatory drugs when taken together is actively discussed. The combination of anticoagulant and anti-inflammatory action in one chemical molecule can solve the problem of polypragmasia.Aim. To study the anti-inflammatory activity of promising 2-hydroxy-4-oxo-4-R-2-butenoates of heterylammonium, which have an effect on the blood clotting system.Materials and methods. For further study of anti-inflammatory activity, 2-hydroxy-4-oxo-4-R-2-butenoates of heterylammonium, which have an effect on the blood clotting system, were selected. The anti-inflammatory effect was studied on a model of acute inflammatory edema in mongrel rats of both sexes weighing 180–250 g. The studied compounds were administered intragastrically. Diclofenac sodium and nimesulide substances administered similarly were used as comparison drugs. Acute toxicity of substances that showed activity was studied on white nonlinear mice of both sexes weighing 18–22 g with the definition of LD50.Results and discussion. All the studied 2-hydroxy-4-oxo-4-R-2-butenoates of heterylammonium have anti-inflammatory effects of varying severity. Data on the study of acute toxicity during intragastric administration, allow us to attribute the studied compounds to the 4.5 class of the hazard classification of chemical products.Conclusion. The anti-inflammatory activity of 14 2-hydroxy-4-oxo-4-R2-butenoates of heterylammonium has been studied. Five butanoate have an effect lower than comparison drugs, eight compounds are comparable to the effect of reference drugs, one compound is superior to nimesulide. The studied compounds can be assigned to class 4,5 of the hazard classification of chemical products. Medicinal candidates have been selected for further pharmacological, toxicological and technological study.

Study of Technological Parameters and Pharmacological Activity of the Gel with Strawberry (<i>Fragaria ananassa</i>) Leaves with Dry Extract

Introduction. Interest in herbal preparations is increasing every year, as the variety of chemical composition and pharmacological action of plants makes it possible to discover and create drugs whose therapeutic effect is due to a complex of biologically active substances. It is important for the effective treatment of diseases to have a properly selected dosage form, which provides both ease of use and targeted use of the action of the pharmacologically active drug contained in it. Therefore, obtaining and introducing new plant extracts into medical practice can become promising in the field of creating soft dosage forms. Strawberry garden leaf extract dry (strawberry extract) is one of the potential substances for obtaining effective and safe medicines. According to the results of earlier studies conducted by the staff of the Perm State Pharmaceutical Academy of the Ministry of Health of the Russian Federation, a high anti-inflammatory activity of strawberry extract was proved, comparable to the activity of the synthetic drug Indomethacin. Studies of the chronic toxicity of the extract, allergenic, immunotoxic properties and reproductive toxicity in the framework of preclinical studies have shown the safety of the obtained extract and the possibility of using the substance for further development of medicines based on it. In this regard, the study of technological parameters and pharmacological activity of a soft dosage form based on strawberry extract is of practical interest for improving the drug supply of the population and expanding the range of medicines based on plant extracts with anti-inflammatory and antimicrobial effects.Aim. Development of a soft dosage form based on strawberry leaves of dry extract and study of its pharmacological activity.Materials and methods. For the study, gels with an active substance – strawberry leaves with dry extract (JSC "Biohimmash", Russia, shelf life – 2 years), the main components – sodium carboxymethylcellulose C75 (TU 2231-002-50277563-2000, LLC "Base chemical products "Yugreactive", Russia, 151118, term storage 3 years), methylcellulose 35 (TU 2231-107-57684455-2003, JSC "UZPH", Russia, 221218, shelf life 3 years), sodium alginate (TU 15-02-544-83, LLC "Base сhemical products "Yugreactive", Russia, 151018, shelf life 3 years), glycerol (FS.2.2.0006.15, JSC "Kupavnareaktiv", Russia, 082018, shelf life 3 years), purified water (FS FS.2.2.0020.18), obtained at the reverse osmosis unit UVOI-"MF" 1812S6 (JSC "NPK MEDIAN FILTER", Russia). Вiopharmaceutical and technological methods were used in the course of the research. Antimicrobial activity was determined according to the OFS.1.2.4.0010.15 by diffusion into agar. Anti-inflammatory activity was studied on a model of acute inflammatory edema caused by subplantar injection of 0.1 ml of 1 % aqueous solution of carrageenan into the hind paw of a rat. The obtained data were processed with the calculation of the Student's t-test for independent samples. The data were considered reliable at p < 0.05.Results and discussion. Based on technological, biopharmaceutical and pharmacological research methods, the composition of a gel from strawberry leaves with dry extract, which has antimicrobial and anti-inflammatory effects, was proposed and substantiated for the first time. The biopharmaceutical availability of the gel was determined by diffusion into agar gel. The antimicrobial activity of the gel from strawberry leaves with dry extract and its anti-inflammatory activity on the model of carrageenan edema with external application of the studied dosage forms were studied.Conclusion. The study shows the possibility of expanding the range of drugs for external use with antimicrobial and anti-inflammatory activity.

Spinal Central Canal Dilation in MOG Antibody-Associated Disease Versus Other CNS Demyelinating Disorders

Objective To assess the frequency of spinal cord central canal dilation on magnetic resonance imaging (MRI) in patients with myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) myelitis compared to myelitis patients with aquaporin-4-positive-neuromyelitis optic spectrum disorder (AQP4+NMOSD) and multiple sclerosis (MS). Background In MOGAD myelitis, a sagittal T2-hyperintense line accompanied by axial T2-signal restricted to the spinal cord gray matter forming an H-sign have been recognized and occur more frequently than in AQP4+NMOSD and MS myelitis. Pseudo-dilation of the ependymal canal has also been highlighted in cases of MOGAD myelitis, but detailed studies of this are lacking. Design/Methods The spinal cord MRIs of myelitis patients with MOGAD (n = 63), AQP4+NMOSD (n = 37), and MS (n = 26) were evaluated for central canal dilation, defined as T2-hyperintensity with similar consistency to cerebrospinal fluid within a myelitis T2-lesion. Clinical data were collected from the medical record for MOGAD patients. The expanded disability status scale (EDSS) was used to quantify disability at nadir. Results The median EDSS score at nadir for the MOGAD myelitis patients was 6 (range: 0-8). MOGAD patients experienced weakness (55/63[87%]), urinary retention/incontinence (50/63[79%]), numbness/paresthesias (48/63[76%]), and stool incontinence/constipation (36/63[57%]). Central canal dilation was more frequent in patients with MOGAD (23/63[37%]) than MS (0/26[0%]); p < 0.001) but did not differ from AQP4+NMOSD (14/37[38%]; p = 0.89). Spinal canal dilation resolved on follow-up axial MRI for most MOGAD (29/34[85%]) and AQP4+NMOSD (13/14[93%]) patients. Conclusions Central canal dilation is a common radiologic accompaniment of acute MOGAD and AQP4+NMOSD myelitis, but not MS myelitis. The resolution of central canal dilation on follow-up MRI in most patients suggests it is transient and related to the acute inflammatory edema. Central canal dilation may differentiate MOGAD and AQP4+NMOSD from MS. Its recognition could facilitate earlier testing for MOG-IgG and AQP4-IgG, accurate diagnosis, and treatment.

LB876 Acute inflammatory edema: A challenging diagnosis in a critically ill patient

A 55-year-old man with a prior history of fibrotic lung disease was admitted to the hospital for bilateral lung transplantation. His post-operational course was complicated by severe volume overload requiring initiation of continuous veno-venous hemodialysis (CVVHD). During this hospitalization, he had developed erythematous plaques over his bilateral thighs. Examination revealed erythematous and edematous plaques with a peau d’orange appearance extending over his bilateral thighs and abdominal pannus. Importantly, the inguinal and infra-abdominal folds were spared. The clinical differential diagnosis included acute inflammatory edema (AIE), early lipodermatosclerosis (LDS), and stasis change. Punch biopsy of a thigh lesion revealed prominent dermal edema, a sparse perivascular and interstitial lymphohistiocytic infiltrate, ectactic vessels, and fibrosis: findings consistent with a diagnosis of AIE. Improvement of the patient’s volume status, increased mobility, and frequent position changes were recommended. AIE is a variant of pseudocellulitis characterized by erythematous and edematous plaques primarily found on the thighs and abdomen that spare areas of increased pressure, such as the inguinal folds. AIE is an acute lymphedema that predominantly affects critically ill patients with hypoalbuminemia, increased body mass index, renal impairment, and evidence of fluid overload. LDS and stasis dermatitis can also present on the thighs and pannus; however, these conditions also commonly manifest on the distal lower extremities and do not spare skin folds. Additionally, LDS and stasis are typically chronic rather than acute. LDS is a lobular panniculitis with fat necrosis, lipomembranous change, and septal fibrosis. In stasis, there are an increased number of thickened capillaries, red blood cell extravasation, and siderophages.

Digital single-operator cholangioscopy for biliary stricture after cadaveric liver transplantation.

BACKGROUNDBiliary strictures after liver transplantation (LT) remain clinically arduous and challenging situations, and endoscopic retrograde cholangiopancreatography (ERCP) has been considered as the gold standard for the management of biliary strictures after LT. Nevertheless, in the treatment of biliary strictures after LT with ERCP, many studies show that there is a large variation in diagnostic accuracy and therapeutic success rate. Digital single-operator peroral cholangioscopy (DSOC) is considered a valuable diagnostic modality for indeterminate biliary strictures.AIMTo evaluate DSOC in addition to ERCP for management of biliary strictures after LT.METHODSNineteen patients with duct-to-duct biliary reconstruction who underwent ERCP for suspected biliary complications between March 2019 and March 2020 at Beijing Chaoyang Hospital, Capital Medical University, were consecutively enrolled in this observational study. After evaluating bile ducts using fluoroscopy, cholangioscopy using a modern digital single-operator cholangioscopy system (SpyGlass DS™) was performed during the same procedure with patients under conscious sedation. All patients received peri-interventional antibiotic prophylaxis. Biliary strictures after LT were classified according to the manifestations of choledochoscopic strictures and the manifestations of transplanted hepatobiliary ducts.RESULTSTwenty-one biliary strictures were found in a total of 19 patients, among which anastomotic strictures were evident in 18 (94.7%) patients, while non-anastomotic strictures in 2 (10.5%), and space-occupying lesions in 1 (5.3%). Stones were found in 11 (57.9%) and loose sutures in 8 (42.1%). A benefit of cholangioscopy was seen in 15 (78.9%) patients. Cholangioscopy was crucial for selective guidewire placement prior to planned intervention in 4 patients. It was instrumental in identifying biliary stone and/or loose sutures in 9 patients in whom ERCP failed. It also provided a direct vision for laser lithotripsy. A space-occupying lesion in the bile duct was diagnosed by cholangioscopy in one patient. Patients with biliary stricture after LT displayed four types: (A) mild inflammatory change (n = 9); (B) acute inflammatory change edema, ulceration, and sloughing (n = 3); (C) chronic inflammatory change; and (D) acute suppurative change. Complications were seen in three patients with post-interventional cholangitis and another three with hyperamylasemia.CONCLUSIONDSOC can provide important diagnostic information, helping plan and perform interventional procedures in LT-related biliary strictures.

Electron Donors Rather Than Reactive Oxygen Species Needed for Therapeutic Photochemical Reaction of Near-Infrared Photoimmunotherapy.

Near-infrared photoimmunotherapy (NIR-PIT) employs molecularly targeted antibodies conjugated with a photoabsorbing silicon-phthalocyanine dye derivative which binds to cancer cells. Application of NIR light following binding of the antibody-photoabsorber conjugates (APCs) results in ligand release on the dye, dramatic changes in solubility of the APC-antigen complex, and rapid, irreversible cell membrane damage of cancer cells in a highly selective manner, resulting in a highly immunogenic cell death. Clinically, this process results in edema after treatment mediated by reactive oxygen species (ROS). Based on the chemical and biological mechanism of NIR-PIT cytotoxicity and edema formation, in order to minimize acute inflammatory edema without compromising therapeutic effects, l-sodium ascorbate (l-NaAA) was administered to quench harmful ROS and accelerate the ligand release reaction. l-NaAA suppressed acute edema by reducing ROS after NIR-PIT yet did not alter the therapeutic effects. NIR-PIT could be performed safely under existence of l-NaAA without side effects caused by unnecessary ROS production.

Hydroxyapatite deposition disease of the wrist with intraosseous migration to the lunate bone

Hydroxyapatite deposition disease (HADD) is a mostly uniarticular, self-limiting condition caused by deposition of hydroxyapatite (HA) crystals in tendons or in the peritendinous soft tissues. Commonly, the glenohumeral joint is affected. More rarely, the HA depot can be cause of a carpal tunnel syndrome due to an acute inflammatory reaction and space-occupying soft tissue oedema. We report a case of acute HA depot located at the volar site of the right wrist with affection of the deep flexor tendons and intraosseous migration into the lunate bone in a 50-year-old female. There are two main goals of this case report: First, to remind the diagnosis of HADD as a cause of wrist pain and also of carpal tunnel syndrome, as this entity being often misdiagnosed clinically, and second, to report a rare case of intraosseous migration of HA crystals into the lunate bone.

Safety and Outcomes Associated with the Pharmacological Inhibition of the Kinin-Kallikrein System in Severe COVID-19.

Background: Coronavirus disease 19 (COVID-19) can develop into a severe respiratory syndrome that results in up to 40% mortality. Acute lung inflammatory edema is a major pathological finding in autopsies explaining O2 diffusion failure and hypoxemia. Only dexamethasone has been shown to reduce mortality in severe cases, further supporting a role for inflammation in disease severity. SARS-CoV-2 enters cells employing angiotensin-converting enzyme 2 (ACE2) as a receptor, which is highly expressed in lung alveolar cells. ACE2 is one of the components of the cellular machinery that inactivates the potent inflammatory agent bradykinin, and SARS-CoV-2 infection could interfere with the catalytic activity of ACE2, leading to the accumulation of bradykinin. Methods: In this case control study, we tested two pharmacological inhibitors of the kinin–kallikrein system that are currently approved for the treatment of hereditary angioedema, icatibant, and inhibitor of C1 esterase/kallikrein, in a group of 30 patients with severe COVID-19. Results: Neither icatibant nor inhibitor of C1 esterase/kallikrein resulted in changes in time to clinical improvement. However, both compounds were safe and promoted the significant improvement of lung computed tomography scores and increased blood eosinophils, which are indicators of disease recovery. Conclusions: In this small cohort, we found evidence for safety and a beneficial role of pharmacological inhibition of the kinin–kallikrein system in two markers that indicate improved disease recovery.

Asthma and COVID-19: a systematic review

BackgroundSevere coronavirus disease-19 (COVID-19) presents with progressive dyspnea, which results from acute lung inflammatory edema leading to hypoxia. As with other infectious diseases that affect the respiratory tract, asthma has been cited as a potential risk factor for severe COVID-19. However, conflicting results have been published over the last few months and the putative association between these two diseases is still unproven.MethodsHere, we systematically reviewed all reports on COVID-19 published since its emergence in December 2019 to June 30, 2020, looking into the description of asthma as a premorbid condition, which could indicate its potential involvement in disease progression.ResultsWe found 372 articles describing the underlying diseases of 161,271 patients diagnosed with COVID-19. Asthma was reported as a premorbid condition in only 2623 patients accounting for 1.6% of all patients.ConclusionsAs the global prevalence of asthma is 4.4%, we conclude that either asthma is not a premorbid condition that contributes to the development of COVID-19 or clinicians and researchers are not accurately describing the premorbidities in COVID-19 patients.

COVID-19 AND BRONCHIAL ASTHMA

Severe coronavirus disease-19 (COVID-19) presents with progressive dyspnea, resulting from acute lung inflammatory edema leading to hypoxia. Asthma has been cited as a potential risk factor for severe COVID-19 like other diseases that affect the respiratory tract. However, so far conflicting results have been published over the last few months and there is still no prove that there is a putative association between these two diseases. In the current mini-review we attempt to summarize the available information from the scientific literature concerning the relation of Bronchial asthma and the severity and clinical course of COVID-19 disease.

SARS-CoV-2 receptor is co-expressed with elements of the kinin\u2013kallikrein, renin\u2013angiotensin and coagulation systems in alveolar cells

SARS-CoV-2, the pathogenic agent of COVID-19, employs angiotensin converting enzyme-2 (ACE2) as its cell entry receptor. Clinical data reveal that in severe COVID-19, SARS-CoV-2 infects the lung, leading to a frequently lethal triad of respiratory insufficiency, acute cardiovascular failure, and coagulopathy. Physiologically, ACE2 plays a role in the regulation of three systems that could potentially be involved in the pathogenesis of severe COVID-19: the kinin–kallikrein system, resulting in acute lung inflammatory edema; the renin–angiotensin system, promoting cardiovascular instability; and the coagulation system, leading to thromboembolism. Here we assembled a healthy human lung cell atlas meta-analysis with ~ 130,000 public single-cell transcriptomes and show that key elements of the bradykinin, angiotensin and coagulation systems are co-expressed with ACE2 in alveolar cells and associated with their differentiation dynamics, which could explain how changes in ACE2 promoted by SARS-CoV-2 cell entry result in the development of the three most severe clinical components of COVID-19.

Novel Enhanced Therapeutic Efficacy of Dapoxetine HCl by Nano-Vesicle Transdermal Gel for Treatment of Carrageenan-Induced Rat Paw Edema.

The aim of this was to develop a well-balanced, replaceable, and patient non-infringing innovative transdermal drug delivery system "nano-vesicle transdermal gel" (NVTG) approaches for inhibiting inflammation. To consummate this objective, we developed a skin permeation nanogel system containing surface active agent along with ethanol. Carbopol 971p, hydroxypropyl methyl cellulose (HPMC K15M), and chitosan were used to fabricate the nanogels. The nanogel system was evaluated for pH, content uniformity, spreadability, rheological studies, in vitro skin permeation, and drug release. Carbapol 971p with the desired in vitro skin permeation was utilized to investigate skin irritation test and effects on inflammation using acute inflammatory paw edema models. Moreover, in vivo pharmacokinetic study was assessed. pH of this nanogels was found within the range of 6.1-7.2, whereas the viscosity was found 310.13 to 6361cps. The ex vivo skin permeation gels showed permeation flux range, 5.9 ± 0.80 to 17.92 ± 1.13μg/cm2h. The highest permeation flux (17.92 ± 1.13μg/cm2h) was observed, which was 3.14-folds higher than that of the plain DH gel (10.72 ± 0.84μg/cm2h. Additionally, from toxicological study, no obvious signs of toxicity such as skin irritation (of laboratory rats) were identified. The in vivo anti-inflammatory behavior in carrageenan-induced rats showed comparatively higher inhibition of rat paw edema swelling by the prepared nanogel compared to that of the plain DH gel and marketed ibuprofen over 6h. The amount of drug accumulated in the skin after topical application was much higher than oral application. In conclusion, developed NVTG formulation loaded with dapoxetine HCl (DH) offers new opportunities for creating novel therapeutic modality for inflammation patients with fewer adverse effects.

Comparative pharmacognostic and pharmacological study of Salvia verticillata and Salvia officinalis leaves to establish the prospect of creating a new medicines

The raw material base of medicinal plants in Ukraine is sufficient only for half of the pharmacopoeial species. Most of them are growing in insufficient quantities and there is a need to import them. In the conditions of import dependence and scarcity of domestic raw materials, the search for new sources of biologically active substances among the representatives of the Ukrainian flora is an urgent aim of modern pharmaceutical science. The purpose of the research is to conduct comparative pharmacognostic and pharmacological studies of S. verticillata and S. officinalis leaves to determine the possibility of using non-pharmacopoeial species in pharmaceutical and medical practice. Materials and methods. The objects of the study are S. verticillata and S. officinalis leaves, which was harvested in the botanical garden of the I. Franko Lviv National University. The morphological and anatomical structure of the species leaves was studied by light microscopy. The study of macro- and microelement composition in the S. officinalis and S. verticillata leaves was carried out by atomic emission spectrographic method. Determination of the qualitative composition and quantitative content of the main groups of biologically active substances was carried out by HPLC. The quantitative determination of phenolic compounds was also carried out by spectrophotometric method. The anti-inflammatory activity of galenic extracts from the leaves of the studied species was studied using a model of acute inflammatory edema caused by subplant implantation of a carrageenin solution. Results. Using light microscopy, we studied the key microscopic and diagnostic signs of S. verticillata leaves. The content of 15 micro and macroelements was found in both studied species. 15 and 14 amino acids, 8 and 6 saponins, respectively, were identified in the S. officinalis and S. verticillata leaves. By HPLC, the qualitative composition and quantitative content of phenolic substances in the S. officinalis and S. verticillata leaves (13 and 12 compounds, respectively) was established. The maximum antiexudative effect of the dry extracts from the S officinalis and S. verticillata leaves was observed at a dose of 50 mg/kg. The dominant of elements are silicon, phosphorus, magnesium, calcium, sodium and potassium. The total content of trace elements in the leaves of S. verticillata is 1.78 times higher than in the pharmacopeia S. officinalis . The total content of saponins predominates in the leaves of S. verticillata and is 15.09 mg/g, which is 12.1 % more than in the pharmacopeia specie. The total flavonoid content in the leaves of S. verticillata is 1.57 times higher than in the pharmacopeia one S. officinalis , the content of hydroxycinnamic acids is highest in the S. officinalis leaves. The highest total content of all phenolic compounds is characteristic of S. verticillata leaves, which is 37.18 % (1.37 times) more than the pharmacopeia S. officinalis . At a dose of 50 mg/kg the anti-inflammatory effect of the dry extract from the S. verticillata leaves was comparable to the activity of the substance from the S. officinalis leaves. Conclusions. As a result of comparative pharmacognostic and pharmacological study of S. verticillata and S. officinalis leaves, it was found that S. verticillata is a promising species for introduction into medical and pharmaceutical practice, precisely as a source of phenolic compounds. The anti-inflammatory effect of the dry extract of S. verticillata leaves was compared with that of the substance of S. officinalis leaves, which indicates the possibility of creating a new anti-inflammatory medicine based on it.

Синтез и биологическая активность N-алкил(арил)-4-R-оксо-2-(2-фениламинобензоилгидразоно)бутанамидов

First of all, the main task of pharmacy is search for new compounds, including those with high biological activity. Although lots of known compounds have antinociceptive and anti-inflammatory effects, almost all of them have a toxic effect on the gastrointestinal tract and cause a large number of side effects from various organs and systems of the body, since they are non-selective inhibitors of cyclooxygenase enzyme. The relief of pain and inflammatory processes as well the following search for safe and more efficient compounds is the significant task of pharmacology. It was found that hydrazonamides have very effective anti-inflammatory and antinociceptive activity; they will be perspective for following pharmacological screening. Objective: synthesis and study of anti-inflammatory and antinociceptive activity of N-alkyl(aryl)-4-R-4-oxo-2-(2-phenylaminobenzoylhydrazono)butanamides. Materials and methods. We synthesized the compounds investigated by means of classic organic synthesis; their structures were analyzed with IR, NMR 1 H, NMR 13 C spectroscopy and mass spectrometry. We studied the antinociceptive activity on outbred white mice by «hot plate» method, and anti-inflammatory activity on outbred white rats by the model of acute inflammatory edema. Results. N-alkyl(aryl)-4-R-4-oxo-2-(2-phenylaminobenzoylhydrazono)butanamides showed the high antinociceptive activity, several compounds exhibited anti-inflammatory effect. Conclusion. N-alkyl(aryl)-4-R-4-oxo-2-(2-phenylaminobenzoylhydrazono)butanamides have perspective for the following in-depth study, including on acute toxicity and other types of biological activity.

Acute inflammatory edema: A mimicker of cellulitis in critically ill patients

Inpatientdermatology consultations for treatment-refractory or atypical cellulitis are common. In critically ill patients, differentiating cellulitis from its mimickers can be challenging. We describe acute inflammatory edema, a likely underrecognized variant of pseudocellulitis. We reviewed the charts of 15 patients with this diagnosis, seen by the inpatient dermatology consultation service at the University of California at San Francisco between 2009 and 2017. The cohort consisted of 9 women and 6 men with an age range of 52-73years. Acute inflammatory edema presents as bilateral, erythematous, and edematous plaques, most commonly involving the thighs and lower abdomen, sparing areas of increased pressure on the skin. There is a predilection for patients with high body mass index and those with clinical or quantitative findings of fluid overload. We propose a 3-part pathogenesis of acute inflammatory edema: 1) acute-onset volume overload 2) in patients with impaired lymphatic return 3) leads to dermal edema, microtears in connective tissue, and an influx of inflammation.

Inflammatory Biomarker Association with Pulmonary Vasoconstriction Versus Blood Oxygenation in a Pig Model of Endotoxin‐Induced Pulmonary Hypertension

Escherichia coli sepsis remains the most mortal cause of early‐onset neonatal sepsis and is characterized by an endotoxin lipopolysaccharide (LPS)‐mediated acute inflammatory response and pulmonary edema. Cytokines are increasingly being evaluated as potential biomarkers for diagnosis of sepsis and monitoring of disease severity but the timing of inflammatory changes in relation to pulmonary hypertension and pulmonary function is unclear.We used a piglet model of endotoxin (ETX)‐induced pulmonary hypertension in the absence of systemic shock to test the hypothesis that pulmonary vasoconstriction versus alveolar gas exchange are mediated by different cytokines. Anesthetized Yorkshire cross piglets (8 kg body weight) were catheterized, and after hemodynamic equilibration, baseline mean arterial pressure, cardiac output, pulmonary arterial pressure, and blood gases were assessed. E. coli endotoxin LPS was administered intravenously (n=10) and carefully titrated (7,500–35,000 units) to achieve pulmonary hypertension without systemic hypotension, and acute lung injury (ALI) criteria of PaO2/FiO2 less than 350 mmHg. Control pigs received normal saline (n=5). Pigs were observed for 18 hours with hemodynamic monitoring and blood was obtained every 2–4 hours for assessment of blood gases and cytokine profiles measured by multiplex magnetic bead assay (Milliplex MAP for Luminex). Hemodynamic measurements, blood oxygenation, and cytokine levels remained constant in the control group. Pulmonary hypertension was seen in the ETX group as evidenced by a mean increase in pulmonary to systemic vascular resistance ratio (PVR/SVR) from 0.16 ± 0.01 to 0.44 ± 0.06 (p<0.05).All 13 inflammatory biomarkers examined (GM‐CSF, INFγ, interleukin (IL)‐1a, IL‐1β, IL‐1ra, IL‐2, IL‐4, IL‐6, IL‐8, IL‐10, IL‐12, IL‐18, and TNF‐α) acutely increased within 2 hours of endotoxin‐induced pulmonary hypertension (ANOVA, p<0.05). Inflammatory marker levels along with PVR/SVR, returned toward baseline levels by 4 hours after ETX exposure and remained no different from controls through 18 hours after ETX. Multiple regression analysis was performed to determine which inflammatory markers in the first 2 hours after ETX may be related to the selective pulmonary vasoactive response to ETX as indicated by the PVR to SVR ratio, versus which markers were associated with reduced pulmonary alveolar gas exchange as reflected by PaO2/FiO2. PVR/SVR was most strongly correlated with IL‐6 and TNF‐α and negatively correlated with IL‐1ra (r=0.92, p<0.01), suggesting that IL‐6 and TNF‐α may be involved in mediating pulmonary vasoconstriction, whereas IL‐1ra antagonizes the vasoactive response to endotoxin. PaO2/FiO2 was positively correlated with IL‐1a, and negatively correlated with INFγ, TNF‐α, IL‐2, and IL‐18 (r=0.93, p<0.01). These findings demonstrate that cytokine changes that accompany endotoxin‐induced pulmonary hypertension occur independent of systemic shock. Further, there appears to be specific differential mediation of the pulmonary vascular response versus pulmonary gas exchange by different cytokines.Support or Funding InformationThis project was funded by the US Army Medical Command. The views expressed in this abstract are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the U.S. Government.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Ziziphora clinopodioides ameliorated rheumatoid arthritis and inflammatory paw edema in different models of acute and chronic inflammation

Ziziphora clinopodioides has been used in traditional medicine for its anti-inflammatory properties. Current study is believed to first time report the potential of Z. clinopodioides extracts to ameliorate joint inflammation using model of chronic joint inflammation (FCA-induced rheumatoid arthritis). The study further investigates the effects on joint inflammation using acute inflammatory paw edema models. The anti-inflammatory effects were also supported by using xylene-induced ear edema model. Results showed that Z. clinopodioides significantly ameliorated rheumatoid arthritis as indicated by the inhibition of arthritic development and paw edema. Histopathological examination showed significant attenuation in pannus formation, bone erosion, and joint inflammation. Treatment with the plant extracts also nearly normalized counts of RBCs, platelets, and total leukocytes along with hemoglobin (Hb) content. Biochemical analysis (AST, ALT, urea, and creatinine) showed that plant extracts did not possess hepatotoxic or nephrotoxic effects. Water displacement plethysmometric analysis showed that Z. clinopodioides significantly attenuated carrageenan-induced paw edema. To evaluate the mechanism, anti-inflammatory effects were further evaluated using histamine- and serotonin-induced inflammatory paw edema models. Z. clinopodioides significantly suppressed paw edema induced by both histamine and serotonin, and also caused the inhibition of xylene-induced ear edema. This suggested the inhibition of autacoids as one of the mechanisms of anti-inflammatory effects of plant. GC–MS analysis showed that the plant is rich in essential oils, including terpenoids, esters, alcohols, furans, cyclic ketones, epoxides, oxanes, and acyclic hydrocarbons. In conclusion, current study demonstrated that Z. clinopodioides possessed significant anti-arthritic and anti-inflammatory properties which might be attributed to the inhibition of autacoids.

PHYTOCHEMICAL ANALYSIS AND IMMUNO-MODULATORY EFFECT OF MORINGA OLEIFERA FLOWERS

Objective: This study evaluates the anti-inflammatory activities of different solvent extracts of Moringa oleifera flowers using carrageenan-induced mice paw edema.Methods: Soxhlet extraction method was employed in this study to extract the crude phytochemicals. Phytochemical analysis testing of Moringa oleifera extracts was performed to identify the presence of various phytoconstituents based on the standard procedures. The anti-inflammatory activity was evaluated using acute inflammatory model carrageenan-induced paw edema. Three different flower extracts (petroleum ether, chloroform and methanol) of Moringa oleifera at the dose level of 500 mg/kg body weight. The anti-inflammatory activity on the different extracts of Moringa oleifera was determined through the α-carrageenan induced left hind paw oedema method in albino mice. 0.05 ml of 1% w/v carrageenan suspension was reconstituted with normal saline (0.9% NaCl) to give a homogenous solution which then be injected into the subplantar tissue of the left hind paw of each mice to induce acute inflammation.Results: Treatment with three different solvent extracts showed significant (p<0.05) inhibition in carrageenan-induced paw edema. Petroleum ether and chloroform extracts were found to be less effective than methanolic extracts when compared to (Indomethacin) reference standard at the dose of 10 mg/kg body weight. The phytochemical results obtained indicates that anti-edematous action of Moringa oleifera flowers exhibited in this study is due to the presence of potent anti-inflammatory phytoconstituents (flavonoid, alkaloid, tannin) in impeding arachidonic acid metabolism and production of reactive free radicals. A significant (p<0.05) increase of left hind paw thickness after the drug injection was noticed in the negative control mice group as time persisted. It showed the highest paw thickness at the fifth hour with 4.72 mm±0.07. Whereas the indomethacin treated group showed the highest percent oedema inhibition amongst all experimental group with 38.60% at the fifth-hour post-carrageenan induction. It exhibited a significant inhibition of 29.02% against the oedema after the third hour of carrageenan injection.Conclusion: The methanolic extract of Moringa oleifera flowers extract has anti-inflammatory activity. This activity was related to the dose and these results collaborate the potential traditional use of the plant in folk medicine.

The In Vitro and In Vivo Anti-Inflammatory Effects of a Phthalimide PPAR-γ Agonist.

Previously, the authors found that 4-hydroxy-2-(4-hydroxyphenethyl) isoindoline-1,3-dione (PD1) (a phthalimide analogue) bound to and activated peroxisome proliferator-activated receptor-γ (PPAR-γ). Since PPAR-γ suppresses inflammatory responses, the present study was undertaken to investigate the anti-inflammatory effects of PD1. In lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophages, PD1 suppressed the inductions of pro-inflammatory factors, including inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase 2 (COX-2), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Concomitantly, PD1 enhanced the expressions of anti-inflammatory factors, such as arginase-1 and interleukin-10 (IL-10), and suppressed LPS-evoked nuclear factor kappa B (NF-κB) p65 subunit phosphorylation in macrophages. In addition, PPAR-γ activated by PD1 was intensively translocated to the nucleus. These observations suggest that the anti-inflammatory mechanism of PD1 involves inhibition of the NF-κB pathway. In a subsequent in vivo animal experiment conducted using a carrageenan-induced acute inflammatory rat paw edema model, intraperitoneal injection of PD1 significantly reduced paw swelling. Histological analysis of rat paw tissue sections revealed less infiltration of immune cells in PD1-pretreated animals. These findings suggest that PD1 be viewed as a lead compound for the development of novel anti-inflammatory therapeutics.