5-LIPOOXYGENASE ACTIVITY IN THE HUMAN VESSEL WALL

1987 ◽  
Author(s):  
WALL R De Caterina ◽  
D Giannessi ◽  
G Lazzerini ◽  
A Mazzone ◽  
A Azzara ◽  
...  

5-lipooxygenase products have been identified from a variety of cells and may play a role in the progression of atherosclerosis and in its clinical manifestations (spasm, thrombosis). We investigated whether human vascular fragments, freshly obtained at surgery, are able to produce leukotriene (LT) B4, a definite end product of 5-lipooxygenase, provided with biological activity. Fragments obtained from human saphenous veins (n=21) or aorta (fibrous plaques, n=15, atheromas, n=16) were incubated in buffer at 37°C with mechanical agitation sequentially in the absence (15 min) and in the presence (15 min) of 10 jjM calcium ionophore A-23187. At the end of each incubation, the buffer was sampled to be assayed by a specific radioimmunassay (RIA) for LTB4 (sensitivity 4.3+0.9 pg). Validation of the assay was performed by comparison with a chemotactic bioassay in Boyden chambers, by interpolation of a standard curve evaluating the chemotactic response of neutrophils to a standard LTB4 preparation. RIA resulted the only practicable method to detect concentrations lower than 2.5 ng/ml, compared both to bioassay and to HPLC, all three performed in the incubation media from 8 vascular fragments. Incubations were also performed in a chamber with selective exposure of the endothelial surface in order to detect possible production of LTB4 on the luminal site of the vessel. Both unstimulated and ionophore-stimulated LTB4 were higher (P< 0.01) in atheromas (2.7±1.2 and 6.3±1.8) than in fibrous plaques (0.51±0.22 and 1.19±0.38) or saphenous veins (0.74±0.34 and 3.07±1.39) (ng/g wet weight, mean±SD). Detectable spontaneous and stimulated LTB4 productions were also found in the incubation media of the chamber with atheromas (40±14 and 324±85 pg/cm2 area, respectively). Histology of the fragments confirmed a higher cellularity (macrophages, atherocytes) in atheromas as compared to fibrous plaques and veins. The human vascular wall is a definite site of 5-lipooxygenase activity, possibly arising from white cell infiltration. LTB4 production, able to reach the inner vessel surface and the blood stream, is a possible factor in the progression of the lesion by increasing vascular permeability or recruiting white blood cells.

Author(s):  
A. Kulikov

Presented material reveals main links in the pathogenesis of hemostatic disorder. In particular, attention is paid to the role of the lungs, liver and other organs in the development of this process. Role of vascular wall and blood cells in regulation of the physical state of blood is described in detail. The most frequent factors leading to hypercoagulation are indicated. Difference between hypercoagulation and thrombophilia is shown. The latter is found in clinical practice quite often, but at the same time, it is poorly diagnosed. Such a terrible complication of hemostatic disorder as disseminated intravascular coagulation is described. Its classification, stages of development, clinical manifestations are offered to the readers.


2016 ◽  
Vol 9 (1) ◽  
pp. 20 ◽  
Author(s):  
Lsmet Nigar ◽  
Shirin Tarafder ◽  
Rehana Razzak Khan ◽  
S. M. Ali Ahmed ◽  
Ahmed Abu Saleh

<p><strong>Background:</strong> Candida species are responsible for various clinical manifestations from mucocutaneous overgrowth to blood stream infections especially in immunocompromized situations. Although C. albicans is the most prevalent species, high incidence of non-albicans Candida species with antifungal resistance are emerging which is posing a serious threat to the patients care.</p><p><strong>Objective:</strong> This study aimed to isolate and identify different species of Candida from different clinical specimens. Methods: A total of 100 different clinical specimens were studied of which 35 were oral swab, 28 were high vaginal swab, 15 were urine, 14 were nail, 04 were bronchoalveolar lavage and peritoneal fluid were 04. Among 100 clinical specimens, Candida isolates were identified in 64 specimens. Isolation of Candida species was done by primary culture in SDA. Subsequent identification of species were performed by germ tube test, subculture in chromo­genic agar medium and carbohydrate assimilation test with commonly used twelve sugars.</p><p><strong>Results:</strong> Out of 64 isolated Candida species, Candida albicans were 51.56% and the non-albicans Candida species were 48.44%. The most prevalent Candida species was C. albicans 33 (51.53%) followed by C. tropicalis 17 (26.56%). C. glabrata 4 (6.25%), C. parapsilo­sis 4 (6.25%), C. krusei 3 (4.68%) and C. guilliermondii 2 (3.2%). One of the isolated Candida species was unidentified.</p><p><strong>Conclusion:</strong> Though Candida albicans was found as the most common species, but non-albicans Candida species are appearing as emerging pathogens as well. Exposure to chemotherapy appeared to be the commonest predisposing factor for Candida infection followed by indwelling urinary catheter in situ for prolong period.</p>


2021 ◽  
Author(s):  
Shiwen Nie ◽  
Yadong He ◽  
Shuo Zhang ◽  
Fenghong Cao

Abstract BackgroundInflammatory pseudotumors that grow on the omentum are relatively rare, and inflammatory pseudotumor most often involves the lung. As far as we know, the inflammatory pseudotumor of omentum, which is in the shape of beaded vesicles and contains gas, has never been reported in the literature. Case presentationwe report a 45-year-old Chinese woman who complained of epigastric pain with hematemesis for 9 hours, physical examination showed subxiphoid tenderness, previous history of gastric ulcer and repair of gastric perforation, laboratory examination showed slight increase of white blood cells and decrease of hemoglobin. Computed tomography showed dotted free gas in the abdominal cavity, and the perforation of the hollow organs was considered. The pathological results after emergency operation showed that histiocyte aggregation with multinucleated giant cell reaction could be seen in the omental tissue. Immunohistochemistry :ER (-), PR (-), PAX-8 (-), CK (mesothelial+), MC (mesothelial+), CR (mesothelial+), CD68 (histiocyte+), SMA (smooth muscle+). The abdominal pain was relieved after surgical resection of the tumor, and recovered well after symptomatic treatment.ConclusionInflammatory pseudotumor of omentum containing gas is easily diagnosed as perforation of hollow organs, with few clinical manifestations of acute abdomen, mostly non-specific, and a good prognosis. Understanding its clinicopathological features and pathological examination methods are helpful to diagnose the disease, so as to choose an appropriate treatment plan, and whether surgical treatment is better than conservative treatment remains to be further studied. The disease should be distinguished from perforation of hollow organs, but the source of gas is unknown. It may have something to do with past medical history.


2021 ◽  
Vol 49 ◽  
Author(s):  
Társsila Mara Vieira Ferreira ◽  
Alexandre Tavares Camelo Oliveira ◽  
Victor Machado De Carvalho ◽  
Ana Débora Nunes Pinheiro ◽  
Thaíse Cristine Ferreira De Carvalho Sombra ◽  
...  

Background: Canine Leishmaniasis (CanL) is a multisystemic and chronic inflammatory disease characterized by nonspecific clinical manifestations. In CanL, inflammatory cells and chemical mediators released in response to the parasite play a role in disease development and progression. Alterations on hematological parameters have been documented in CanL. These changes can also be assessed in relation to systemic inflammation caused by this disease. The circulating leukocyte counting, such as neutrophils, as well as the albumin level, are considered direct indicators of an inflammatory host environment. Several studies point to the use of biomarkers on the assistance in diagnosis and prognosis of several canine pathologies. The present study investigated the Neutrophils to Lymphocyte Ratio (NLR), Albumin to Globulin Ratio (AGR), and Neutrophils to Albumin Ratio (NAR) on systemic inflammatory response induced by Canine Leishmaniasis (CanL).Materials, Methods & Results: For this purpose, adult dogs with confirmed diagnosis to CanL were divided into symptomatic (SD, n = 33) and asymptomatic (AD, n = 20) dogs for L. infantum and control dogs (CD, n = 20). Routine hematological and biochemical parameters were determined in blood samples using a veterinary automatic hematology and biochemical analyzers. Asymptomatic dogs (AD) had a higher number of white blood cells and neutrophils (16.48 ± 4.93; 13.41 ± 3.60, respectively) in relation to symptomatic dogs (SD) (13.54 ± 5.13; 10.42± 3.69, respectively) (P = 0.015 and P < 0.0001, respectively). Neutrophils to Lymphocyte Ratio (NLR) was higher in dogs with leishmaniasis (9.45 ± 3.76) than in healthy dogs (3.39 ± 1.19) (P < 0.0001). Serum total proteins (STP) and globulins increased in CanL, while albumin and AGR decreased in CanL, when compared to CD and references values to canine species. Neutrophils to Albumin Ratio (NAR) was higher in AD and SD (5.02 ± 1.14; 4.79 ± 1.07, respectively) when compared to CD (2.36 ± 0.55) (P < 0.0001). Discussion: As reported in scientific researches, dogs with Leishmaniasis present alterations in circulating cell counts. Based on these data, we decided to expand this information using the NLR as a parameter in an attempt to better clarify the changes in these cells in CanL. We observed that NLR was increased on CanL in relation to healthy dogs, which could be a consequence of relative neutrophilia rather than lymphopenia. Neutrophils to Lymphocyte Ratio (NLR) is a biomarker that conveys information about inflammatory conditions. An elevated NLR can reflect an upregulated innate immune response, since neutrophils are effector cells of innate immunity and are involved in several acute and chronic inflammatory processes. Albumin is an acute phase protein that is considered an immune-inflammatory biomarker, which can be found reduced systemically in progressive inflammatory response. Serum total proteins (STP) and globulins were increased in CanL. These data are already well documented in CanL, which serum globulins are mainly associated with the increase of acute phase proteins, cytokines, and increase of specific antibodies to Leishmaniainfantum. Our results showed neutrophilia with hypoalbuminemia in CanL. So, in an attempt to assess the relationship of these two available markers, we used NAR calculation in order to evaluate the changes induced by CanL. In this study NAR was higher in CanL when compared to control dogs. Thus, our data indicate that NLR and NAR could be used as biomarkers in veterinary medical clinics in order to assess inflammatory profile in CanL, mainly in asymptomatic dogs. These parameters obtained from routine blood tests might be useful as cost-effective, easily accessible and helpful markers in order to distinguish the inflammatory response intensity in CanL.


1979 ◽  
Author(s):  
B. Lipinski ◽  
L.J. Machlin

DIC in rabbits was induced by i.v, injection of E. coli endotoxin (e) (50μg/kg). The levels of fibrinogen (F) and FDP, fibrin monomer (FM), PTT, white blood cells and platelet counts were determined before and 3 hours after e injection. Fibrin (f) deposited in organs was calculated by counting the radioactivity of 125I-F introduced i.v, beforehand. Pretreatment of rabbits, maintained on laboratory chow, with dl-α-tocopheryl acetate (vit. E) (40mg/kg/day i.m. for 3 days) did not protect the animals against U1C induced with 2 doses of e 24 hours apart, and only slightly reduced amounts of f deposited in organs. On the other hand, rabbits maintained on a vit. E-deficient diet were found to be extremely sensitive to e. Single doses of e caused 100% mortality within 24 hours, as compared to 100% survival in a group fed the same diet containing vit. E. Laboratory findings (F depletion, presence of FM, increased FDP and prolonged PTT) and increased f deposition in organs (kidneys, lung, liver and spleen) indicated activation of intravascular coagulation by a single dose of c in vit. E-deficient rabbits. It is possible that normal levels of vit. E protect against cell injury by e and thus prevent a release of procoagulants into the blood stream.


1987 ◽  
Author(s):  
G Bashkov ◽  
T Kalishevekaya ◽  
S Strukova

The role of the endothelial injury in the development of the thrombophylic state was studied in rats with nephrotic syndrome (NS,Heymann nephritis).There were a 6-fold increase of the soluble fibrin concentration and a 30% decrease of plasma antithrombin III (AT) activity in the NSIt was found that the plasma half-life of 125 J-labelled α-thrombin (10-7 M) is 3,0 ± 0,6 min in control animals and 4,0 ± 0,1 min in NS rats. At 20 min following the administration of bovine 125J-thrombin it was observed that in normal animals 84% of the radiolabelled enzyme was bound with vessel wall.while in NS rats the figure was only 63% (p< 0,05). The alteration of thrombin binding to the vascular wall lead to an increase in the amount of soluble fibrin-monomer and AT-proteinase complexes.AT-thrombin complexes and a proteolytically modified form of AT (Mr<68 kDa) were isolated from NS rats plasma by affinity chromatography on heparin-sepharose and chromatofocusing.At 3 min following injection of a 100-fold molar excess of bovine AT (1,7 .10-5 M) it was observed that 35% of thrombin reversibly bound to the endothelium could be detected in the circulation of normal rats. The same excess of AT induced only a 10% (p<0,001) release of 125J-thrombin to the blood stream in the NS rats through the formation of 125 J-thrombin complexes with Mr≥100 kDa.It is being proposed that injury of the vascular wall in the NS animals facilitated the interaction of the enzyme with the substrate (fibrinogen) and inhibitor (AT), and leads to ineffective inactivation of thrombin bound to the endothelium by AT.


2019 ◽  
Vol 15 (3) ◽  
pp. 431-438
Author(s):  
E. L. Trisvetova

Fibromuscular dysplasia of the coronary arteries is a rare non-atherosclerotic and non-inflammatory vascular lesion that is asymptomatic until serious complications develop: stenosis, dissection, rupture, sudden cardiac death. Since there are no long-term numerous clinical observations of patients with fibromuscular dysplasia of the coronary arteries, recommendations have not been developed for diagnosing and treating the disease, which often manifests with acute coronary syndrome. In 2014, the European Consensus was published, and in 2019, the first international consensus document on the diagnosis and treatment of fibromuscular dysplasia with lesions of vessels from different regions (renal, cerebrovascular, coronary, and others). The documents state that the development of fibromuscular dysplasia of the coronary arteries considers the participation of the PHACTR1 gene mutation and the transcriptional activity of the EDN1 gene, smoking, prolonged exertion of the vascular wall, and possibly female sex hormones. In the case of acute coronary syndrome, the most informative diagnostic method is computed tomography with angiography, which reveals a smooth narrowing of the lumen in the middle or distal section in the epicardial artery, often due to intramural hematoma, and also finds dissection, spasm, and tortuous vessel. Additional diagnostic methods ‒ intravascular ultrasound and optical coherence tomography allow differentiation of fibromuscular dysplasia with atherosclerosis of the coronary artery, vasculitis, and other diseases. The choice of treatment tactics for fibromuscular dysplasia of the coronary arteries depends on the severity of the clinical manifestations ‒ conservative medical treatment and interventional methods are used.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S623-S624
Author(s):  
Michael D Lum ◽  
Kelsey Reardon ◽  
Rachel Spector ◽  
Evan Garry ◽  
Aikaterini Papamanoli ◽  
...  

Abstract Background Current literature presents conflicting results regarding the clinical manifestations of coinfection with Babesia microti (Babesiosis) and Borrelia burgdorferi (Lyme disease). The aim of this study is to investigate the effect that coinfection with Babesiosis and Lyme Disease has on standard and novel biomarkers markers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and procalcitonin (Pc), which may assist in elucidating how these pathogens interact within human hosts. Methods Babesia cases were collected from Stony Brook University Hospital from 2012 to 2019. Cases of Babesia were included if parasites were detected by peripheral blood smear and confirmed by PCR. Lyme disease diagnosis criteria involved 2-tier testing per CDC guidelines. Cases were divided into three cohorts based on if they had CRP, ESR or Pc tested. Cohorts were divided into two groups: Babesiosis alone vs coinfection with Lyme Disease. Median values were analyzed for the following biomarkers across both groups: parasitemia, hemoglobin (Hgb), white blood cells (WBC), platelets, indirect bilirubin (IB), lactate dehydrogenase, ESR, CRP and Pc. Fisher Exact and Wilcoxon Rank sum tests were used and P values &lt; 0.05 were considered statistically significant. Results ESR values trended higher in monoinfection compared to coinfection (50 vs 36 mm/hr, p=0.63). Within this cohort, the coinfection group had significantly lower platelet values compared to monoinfection (52 vs. 75.5 K/uL, p=0.04, Table 1). Within the CRP and Pc cohorts, monoinfection had higher trends of parasitemia compared to coinfection (CRP group: 1.6 vs 0.7%, p=0.14, Pc group: 1.4 vs 0.7% p=1.0, Table 2&3). Pc levels were similar in both groups (1.1 vs 1.2 ng/mL, p=1.0, Table 3). Table 1: Demographics and Biomarkers for Patients with Babesiosis Monoinfection vs. Coinfection with Babesiosis and Lyme Disease that had ESR Measured. Table 2: Demographics and Biomarkers for Patients with Babesiosis Monoinfection vs. Coinfection with Babesiosis and Lyme Disease that had CRP Measured. Table 3: Demographics and Biomarkers for Patients with Babesiosis Alone vs Coinfection with Babesiosis and Lyme Disease that had Procalcitonin Measured. Conclusion Coinfection had significantly lower platelets within the ESR cohort but not in other cohorts. While not statistically significant, monoinfection showed greater trends of ESR and parasitemia, which is consistent with previous studies that suggest that B. burgdorferi may mitigate the effects of B. microti infection. CRP and Pc levels were similar across both groups suggesting that the utility of using novel biomarkers to elucidate the interaction between B. burgdorferi and B. microti during simultaneous infection requires further study. Disclosures All Authors: No reported disclosures


1960 ◽  
Vol 112 (4) ◽  
pp. 619-634 ◽  
Author(s):  
Henry H. Freedman

The effect of various schedules for inducing tolerance to bacterial endotoxin in donor rabbits upon suitability for demonstration of passive transfer of tolerance to pyrogenicity in normal recipients has been investigated. Long-term treatment of donors, through 5 weeks, is no more effective than a brief series of injections, adding further evidence that tolerance is not attributable to specific antibody to the endotoxin. Qualitative differentiation of the febrile pattern of passively tolerant recipients from that seen in control animals depends upon the magnitude of the test dose of pyrogen. Passively tolerant rabbits respond to endotoxin with an acute leucopenia equivalent to that seen in controls suffering a full biphasic fever. Animals given daily injections of endotoxin continue to show the acute leucopenia, despite the early modification of the course of fever characteristic of endotoxin tolerance. The assumption that the leucopenia reflects damage to the leucocytes, with release of endogenous pyrogen, is not consistent with these findings. Rabbits rendered leucopenic by nitrogen mustard and then given endotoxin exhibit a rapidly developing fever of greater than normal intensity, the exaggeration of the febrile response being proportional to the severity of the induced leucopenia. The implications of these findings for the pathogenesis of endotoxin-induced fever are discussed. The evidence supports the hypothesis that endotoxin produces fever by direct action rather than by release of endogenous leucocytic pyrogen. It is postulated that the lesser fever, in animals having normal numbers of circulating leucocytes, reflects a limitation of available endotoxin by the known rapid sequestration in the white blood cells at the time of the acute leucopenia. It is further suggested that the biphasic febrile response of the normal rabbit results from reinoculation of the blood stream by the temporarily sequestered endotoxin, the RES of the tolerant animal clearing the released endotoxin at a rate sufficient to prevent triggering the second phase of fever.


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