scholarly journals About Minimization of Expenses on Allergy Diagnosis in Children: Analysis of Consistency of in Vitro- and in Vivo-Allergic Examinations Results

2015 ◽  
Vol 70 (6) ◽  
pp. 748-755
Author(s):  
Marina Andreevna Snovskaya ◽  
Anna Sergeevna Batyrova ◽  
Leyla Seymurovna Namazova-Baranova ◽  
Anna Aleksandrovna Alekseeva ◽  
Elena Aleksandrovna Vishneva ◽  
...  
Keyword(s):  
Atopic Disease ◽  
Skin Tests ◽  
Morbidity Rate ◽  
In Vitro Tests ◽  
High Morbidity ◽  
Meadow Fescue ◽  
Ige Antibodies ◽  
High Morbidity Rate

High morbidity rate of atopic diseases among children, including high importance of grass pollen as a sensitizing agent, determine the relevance of studies on diagnostic examination systems for appointment of adequate therapy. The research of the most relevant allergens for patients to exclude of duplicating and uninformative tests became urgent after development of a new type of diagnostic tests that does not require expensive equipment. The objective of this research was to evaluate the results of in vitro- and in vivo-diagnostic examinations of children with various forms of atopic disease caused by pollen of meadow grasses, and to choose the most significant prognostic parameters for the diagnosis. Methods: 277 children aged 4–16 years with various forms of atopic disease were included in the study. There were performed skin prick tests and determination of IgE-antibodies levels to allergen extracts of cocksfoot (g3), meadow fescue (g4), timothy grass (g6). Results: In the studied group of patients 32–50% of children have antibodies to grass allergens. There was a close correlation of antibody response on the investigated allergens, quantitative coincidence of IgE-antibodies to g3 and g4 allergens levels. IgE (g6) concentration was close to the IgE(g3) and IgE(g4) levels (85,0±21,6%). Analysis of the skin tests results showed that 44% of patients have a positive response to grass allergens, and in vivo-tests results coincide with serological tests results, mostly in a qualitative sense. The most significant relationship was noted between in vivo and in vitro-tests in the results of testing the response to meadow fescue pollen.Conclusion: Based on these data IgE concentration index to meadow fescue allergens can be used as a prognostic marker to determine the sensitization of patients with different nosology forms of allergy and can help to improve allergic diagnostics.

Role of in vivo and in vitro Tests in the Diagnosis of Severe Cutaneous Adverse Reactions (SCAR) to Drug

2019 ◽  
Vol 25 (36) ◽  
pp. 3872-3880 ◽  
Author(s):  
Marcel M. Bergmann ◽  
Jean-Christoph Caubet
Keyword(s):  
Adverse Reactions ◽  
Lymphocyte Transformation ◽  
Stevens Johnson Syndrome ◽  
In Vitro Tests ◽  
High Morbidity ◽  
Patch Tests ◽  
Severe Cutaneous Adverse Reactions ◽  
Cutaneous Adverse Reactions

Severe cutaneous adverse reactions (SCAR) are life-threatening conditions including acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Diagnosis of causative underlying drug hypersensitivity (DH) is mandatory due to the high morbidity and mortality upon re-exposure with the incriminated drug. If an underlying DH is suspected, in vivo test, including patch tests (PTs), delayed-reading intradermal tests (IDTs) and in vitro tests can be performed in selected patients for which the suspected culprit drug is mandatory, or in order to find a safe alternative treatment. Positivity of in vivo and in vitro tests in SCAR to drug varies depending on the type of reaction and the incriminated drugs. Due to the severe nature of these reactions, drug provocation test (DPT) is highly contraindicated in patients who experienced SCAR. Thus, sensitivity is based on positive test results in patients with a suggestive clinical history. Patch tests still remain the first-line diagnostic tests in the majority of patients with SCAR, followed, in case of negative results, by delayed-reading IDTs, with the exception of patients with bullous diseases where IDTs are still contra-indicated. In vitro tests have shown promising results in the diagnosis of SCAR to drug. Positivity is particularly high when the lymphocyte transformation test (LTT) is combined with cytokines and cytotoxic markers measurement (cyto-LTT), but this still has to be confirmed with larger studies. Due to the rarity of SCAR, large multi-center collaborative studies are needed to better study the sensitivity and specificity of in vivo and in vitro tests.

scholarly journals Antiviral activity of N-ω-Chloroacetyl-L-Ornithine on in vitro replication of Chikungunya virus

2019 ◽  
Author(s):  
Lucero Luna-Rojas ◽  
Amanda M. Avila-Trejo ◽  
Verónica Alcántara-Farfán ◽  
Lorena I. Rodríguez-Páez ◽  
Marvin Omar Pastor-Alonso ◽  
...  
Keyword(s):  
Viral Replication ◽  
Ornithine Decarboxylase ◽  
Health Problem ◽  
Cytotoxic Effect ◽  
Chikungunya Virus ◽  
Competitive Inhibitor ◽  
Morbidity Rate ◽  
High Morbidity ◽  
High Morbidity Rate

AbstractThe infections causes by Chikungunya virus (CHIKV), family Togaviridae, genus Alfavirus, have become a health problem around the world, due to its widespread occurrence, the high morbidity rate and the absence of vaccines or antiviral treatments. We analyzed a competitive inhibitor of ornithine decarboxylase, enzyme key in the biosynthesis of Polyamines (PAs), N-ω-chloroacetyl-L-ornithine (NCAO), as a possible inhibitor of CHIKV replication because intracellular polyamines participate in the transcription and in vitro translation of CHIKV. NCAO does not have any cytotoxic effect on C6/36 cells even at a concentration of 1000μM at 72h after post-exposure but in Vero cells the cytotoxic effect was presented above 380μM at 48h post-exposure, which was considered when determining the inhibitory effect on viral replication. We demonstrate that NCAO inhibits the replication of CHIKV in Vero and C6/36 cells in a dose-dependent manner causing a decrease in the PFU/mL of at least 4-logarithm (p <0.01) in both cell lines. Viral yields were restored by the addition of exogenous polyamines, mainly putrescine. HPLC analyses it shown that NCAO decrease content of intracellular PAs even though in infected cells mainly decreased spermidine and spermine, so NCAO inhibits CHIKV replication, by depleting the intracellular polyamines in Vero and C6/36 cells, suggesting that this compound is a possible antiviral in CHIKV infections.ImportanceThe infections caused by Chikungunya virus (CHIKV), genus Alfavirus, have become a worldwide health problem, due to its high morbidity rate and the absence of vaccines or antiviral treatments. It is known that CHIKV use intracellular poliamines during transcription and traduction process, so the depletion of intracellular putrescine, spermidine and spermine reduce the viral replication. N-ω-chloroacetyl-L-ornithine (NCAO) is known as a competitive inhibitor of ornithine decarboxylase, key enzyme in Polyamines biosynthesis, but no studies have proven its activity on the inhibition of polyamine-dependent viral replication. Here we demonstrate NCAO inhibits in vitro CHIKV replication, so we propose NCAO as an antiviral candidate.

In Silico Insights on GD2 : A Potential Target for Pediatric Neuroblastoma

2020 ◽  
Vol 19 (30) ◽  
pp. 2766-2781 ◽  
Author(s):  
Akanksha Limaye ◽  
Jajoriya Sweta ◽  
Maddala Madhavi ◽  
Urvy Mudgal ◽  
Sourav Mukherjee ◽  
...  
Keyword(s):  
In Silico ◽  
Electrostatic Interactions ◽  
3D Structure ◽  
Biological Marker ◽  
Morbidity Rate ◽  
Local Alignment ◽  
Pharmacokinetic Studies ◽  
High Morbidity ◽  
High Morbidity Rate

Background: Originating from the abnormal growth of neuroblasts, pediatric neuroblastoma affects the age group below 15 years. It is an aggressive heterogenous cancer with a high morbidity rate. Biological marker GD2 synthesised by the GD2 gene acts as a powerful predictor of neuroblastoma cells. GD2 gangliosides are sialic acid-containing glycosphingolipids. Differential expression during brain development governs the function of the GD2. The present study explains the interaction of the GD2 with its established inhibitors and discovers the compound having a high binding affinity against the target protein. Technically, during the development of new compounds through docking studies, the best drug among all pre-exist inhibitors was filtered. Hence in reference to the best docked compound, the study proceeded further. Methodology: The In silico approach provides a platform to determine and establish potential inhibitor against GD2 in Pediatric neuroblastoma. The 3D structure of GD2 protein was modelled by homology base fold methods using Smith-Watermans’ Local alignment. A total of 18 established potent compounds were subjected to molecular docking and Etoposide (CID: 36462) manifested the highest affinity. The similarity search presented 336 compounds similar to Etoposide. Results: Through virtual screening, the compound having PubChem ID 10254934 showed a better affinity towards GD2 than the established inhibitor. The comparative profiling of the two compounds based on various interactions such as H-bond interaction, aromatic interactions, electrostatic interactions and ADMET profiling and toxicity studies were performed using various computational tools. Conclusion: The docking separated the virtual screened drug (PubChemID: 10254934) from the established inhibitor with a better re-rank score of -136.33. The toxicity profile of the virtual screened drug was also lesser (less lethal) than the established drug. The virtual screened drug was observed to be bioavailable as it does not cross the blood-brain barrier. Conclusively, the virtual screened compound obtained in the present investigation is better than the established inhibitor and can be further augmented by In vitro analysis, pharmacodynamics and pharmacokinetic studies.

Immediate Allergic Reactions to β-Lactams: Diagnosis and Therapy

2003 ◽  
Vol 16 (1) ◽  
pp. 19-23 ◽  
Author(s):  
A. Romano ◽  
C. Mondino ◽  
M. Viola ◽  
P. Montuschi
Keyword(s):  
Anaphylactic Shock ◽  
Specific Ige ◽  
Ring Structure ◽  
Skin Tests ◽  
In Vitro Tests ◽  
Allergic Reactions ◽  
In Vitro Test ◽  
Immunological Mechanisms

β-Lactams are the antibiotics which most frequently provoke adverse reactions mediated by specific immunological mechanisms. These reactions, classifiable as immediate or non-immediate, can be produced by the four classes of β-lactams (penicillins, cephalosporins, carbapenems and monobactams) currently available, which share a common β-lactam ring structure. Immediate reactions occur within the first hour after drug administration and are characterized by urticaria, angioedema, rhinitis, bronchospasm, and anaphylactic shock. Immediate reading skin tests are the quickest and most reliable method for demonstrating the presence of β-lactam specific IgE antibodies. It is crucial to use in diagnosis the suspected β-lactams themselves, particularly cephalosporins, in addition to penicillin determinants. Serum specific IgE assays can be used as complementary tests. Negative test results should be interpreted in light of the time elapsed from the last exposure to the responsible β-lactam. In fact, both in vivo and in vitro test sensitivity is known to decrease over time. In some diagnostic work-ups, patients with a positive history and negative skin and in vitro tests with classic reagents undergo a controlled administration of the suspected β-lactam. The management of immediate allergic reactions should take into consideration their severity and type. Adrenaline is the drug of choice in the treatment of anaphylactic shock. In addition to adrenaline, corticosteroids and antihistamines should be administered. Histamine H1 receptor antagonists are the mainstay of the treatment of immediate allergic reactions such as urticaria, rhinitis and conjunctivitis.

scholarly journals Approaches to the Management of Presumed Immediate Hymenoptera Venom Allergy and Non-Detectable IgE

2010 ◽  
Vol 3 (1) ◽  
pp. 16-23
Author(s):  
Ervin Ç. Mingomataj ◽  
Alketa H. Bakiri
Keyword(s):  
Skin Test ◽  
Case Reports ◽  
Skin Tests ◽  
Diagnostic Tools ◽  
In Vitro Tests ◽  
Insect Allergy ◽  
History Of ◽  
Cellular Tests

Objective: To provide a comprehensive evaluation in patients with a convincing history of immediate insect allergy but negative skin test and/or specific IgE results, adequately addressing the question of how best to manage them. Data sources: Observational peer-reviewed studies and case reports were searched on Pub-Med database from 1998 up to March 2009 using the following keywords: Hymenoptera Allergy & Negative IgE (Negative Skin Tests). Study selection: Studies on supplemental diagnostic tests that provided data from patients with immediate hymenoptera allergy but negative conventional tests results to the offending allergens were selected. In this work, we also included studies providing additional relevant information regarding this issue. Results: Among 43 identified papers only 9 of them presented relevant original data, while the other papers were reviews. In the majority of the cases, the culprit insect was identified with in vitro tests such as Basophil Activation Test, Cellular Allergen Stimulation Test or Western blot, whereas in vivo (less frequently) with sting challenge or dialyzed venom skin test. Conclusions: The management of patients with a convincing history of immediate insect allergy but negative conventional test results requires an adaption of the guidelines including an incorporation of the novel diagnostic tools. Although cellular tests represent equivalent sensitivity and superior specificity as compared with standard ones, these tests still remain supplementary diagnostic tools. In a minority of cases (especially in the developing countries where cellular tests cannot be performed), venom immunotherapy in adult subjects could be taken into account based solemnly on the history of a clear patient’s identification of the culprit insect.

scholarly journals Antiviral Activity of N-ω-Chloroacetyl-L-Ornithine on In Vitro Replication of the Chikungunya Virus

2020 ◽  
Author(s):  
Lucero Luna-Rojas ◽  
Amanda Marineth Avila-Trejo ◽  
Veronica Alcantara-Farfán ◽  
Lorena I Rodriguez-Paez ◽  
Marvin Omar Pastor-Alonso ◽  
...  
Keyword(s):  
Cytotoxic Effect ◽  
Chikungunya Virus ◽  
Vero Cells ◽  
Competitive Inhibitor ◽  
Morbidity Rate ◽  
High Morbidity ◽  
Dependent Manner ◽  
Post Exposure ◽  
High Morbidity Rate

The infections caused by Chikungunya virus (CHIKV), genus Alphavirus, have become a health problem around the world, due to this virus&rsquo;s widespread occurrence and high morbidity rate and the absence of vaccines or antiviral drugs. In this study, we analyzed a competitive inhibitor of ornithine decarboxylase&mdash;an enzyme that is key in the biosynthesis of polyamines (PAs), N-&omega;-chloroacetyl-L-ornithine (NCAO), which is a possible inhibitor of CHIKV replication because intracellular polyamines participate in the in vitro transcription and translation of CHIKV. NCAO does not have any cytotoxic effect on C6/36 cells even at 1000 &mu;M at 72 h post-exposure. However, in Vero cells, a cytotoxic effect was present above 380 &mu;M at 48 h post-exposure, which was considered when determining the inhibitory effect on viral replication. In this work, we demonstrate that NCAO inhibits the replication of CHIKV in Vero and C6/36 cells in a dose-dependent manner, causing a decrease in the PFU/mL of at least 4 logarithms (p &lt;0.01) in both cell lines. Viral yields were restored by the addition of exogenous polyamines, mainly putrescine. The HPLC analyses showed that NCAO decreases the content of intracellular PAs, even though mainly spermidines and spermines are present in infected cells. NCAO inhibits CHIKV replication by depleting the intracellular polyamines in Vero and C6/36 cells, suggesting that this compound is a possible antiviral for CHIKV infections.

Comparison of High Purity Factor IX Concentrates and a Prothrombin Complex Concentrate in a Canine Model of Thrombogenicity

1991 ◽  
Vol 66 (05) ◽  
pp. 609-613 ◽  
Author(s):  
I R MacGregor ◽  
J M Ferguson ◽  
L F McLaughlin ◽  
T Burnouf ◽  
C V Prowse
Keyword(s):  
High Purity ◽  
Time Course ◽  
Prothrombin Complex Concentrate ◽  
Degradation Products ◽  
Canine Model ◽  
Factor Ix ◽  
In Vitro Tests ◽  
Albumin Infusion

SummaryA non-stasis canine model of thrombogenicity has been used to evaluate batches of high purity factor IX concentrates from 4 manufacturers and a conventional prothrombin complex concentrate (PCC). Platelets, activated partial thromboplastin time (APTT), fibrinogen, fibrin(ogen) degradation products and fibrinopeptide A (FPA) were monitored before and after infusion of concentrate. Changes in FPA were found to be the most sensitive and reproducible indicator of thrombogenicity after infusion of batches of the PCC at doses of between 60 and 180 IU/kg, with a dose related delayed increase in FPA occurring. Total FPA generated after 100-120 IU/kg of 3 batches of PCC over the 3 h time course was 9-12 times that generated after albumin infusion. In contrast the amounts of FPA generated after 200 IU/kg of the 4 high purity factor IX products were in all cases similar to albumin infusion. It was noted that some batches of high purity concentrates had short NAPTTs indicating that current in vitro tests for potential thrombogenicity may be misleading in predicting the effects of these concentrates in vivo.

A Comparison of the in Vitro and in Vivo Thrombogenic Activity of Factor IX Concentrates Using Stasis (Wessler) and Non-Stasis Rabbit Models

1980 ◽  
Vol 44 (02) ◽  
pp. 081-086 ◽  
Author(s):  
C V Prowse ◽  
A E Williams
Keyword(s):  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Factor Ix ◽  
Coagulation System ◽  
In Vitro Tests ◽  
Clinical Use ◽  
Low Activity

SummaryThe thrombogenic effects of selected factor IX concentrates were evaluated in two rabbit models; the Wessler stasis model and a novel non-stasis model. Concentrates active in either the NAPTT or TGt50 in vitro tests of potential thrombogenicity, or both, caused thrombus formation in the Wessler technique and activation of the coagulation system in the non-stasis model. A concentrate with low activity in both in vitro tests did not have thrombogenic effects in vivo, at the chosen dose. Results in the non-stasis model suggested that the thrombogenic effects of factor IX concentrates may occur by at least two mechanisms. A concentrate prepared from platelet-rich plasma and a pyrogenic concentrate were also tested and found to have no thrombogenic effect in vivo.These studies justify the use of the NAPTT and TGt50 in vitro tests for the screening of factor IX concentrates prior to clinical use.

Inhibition of Fibrinolysis and Fibrinogenolysis in Man: Comparison of ε-Aminocaproic Acid and Kallikrein Inhibitor

1963 ◽  
Vol 10 (01) ◽  
pp. 106-119 ◽  
Author(s):  
E Beck ◽  
R Schmutzler ◽  
F Duckert ◽  
Keyword(s):  
Aminocaproic Acid ◽  
Side Reactions ◽  
In Vitro Tests ◽  
Factor V ◽  
Clinical Use ◽  
Strong Inhibitor ◽  
Kallikrein Inhibitor ◽  
Therapeutic Possibilities

SummaryInhibitor of kallikrein and trypsin (KI) extracted from bovine parotis was compared with ε-aminocaproic acid (EACA): both substances inhibit fibrinolysis induced with streptokinase. EACA is a strong inhibitor of fibrinolysis in concentrations higher than 0, 1 mg per ml plasma. The same amount and higher concentrations are not able to inhibit completely the proteolytic-side reactions of fibrinolysis (fibrinogenolysis, diminution of factor V, rise of fibrin-polymerization-inhibitors). KI inhibits well proteolysis of plasma components in concentrations higher than 2,5 units per ml plasma. Much higher amounts of KI are needed to inhibit fibrinolysis as demonstrated by our in vivo and in vitro tests.Combination of the two substances for clinical use is suggested. Therapeutic possibilities are discussed.

Hemostatic wound dressings: Predicting their effects by in vitro tests

2019 ◽  
Vol 33 (9) ◽  
pp. 1285-1297 ◽  
Author(s):  
Cornelia Wiegand ◽  
Martin Abel ◽  
Uta-Christina Hipler ◽  
Peter Elsner ◽  
Michael Zieger ◽  
...  
Keyword(s):  
Blood Clot ◽  
Wound Dressings ◽  
In Vitro Tests ◽  
Regenerated Cellulose ◽  
Oxidized Regenerated Cellulose ◽  
Inflammatory Reactions ◽  
In Vitro Techniques ◽  
Cotton Gauze

Background Application of controlled in vitro techniques can be used as a screening tool for the development of new hemostatic agents allowing quantitative assessment of overall hemostatic potential. Materials and methods Several tests were selected to evaluate the efficacy of cotton gauze, collagen, and oxidized regenerated cellulose for enhancing blood clotting, coagulation, and platelet activation. Results Visual inspection of dressings after blood contact proved the formation of blood clots. Scanning electron microscopy demonstrated the adsorption of blood cells and plasma proteins. Significantly enhanced blood clot formation was observed for collagen together with β-thromboglobulin increase and platelet count reduction. Oxidized regenerated cellulose demonstrated slower clotting rates not yielding any thrombin generation; yet, led to significantly increased thrombin-anti-thrombin-III complex levels compared to the other dressings. As hemostyptica ought to function without triggering any adverse events, induction of hemolysis, instigation of inflammatory reactions, and initiation of the innate complement system were also tested. Here, cotton gauze provoked high PMN elastase and elevated SC5b-9 concentrations. Conclusions A range of tests for desired and undesired effects of materials need to be combined to gain some degree of predictability of the in vivo situation. Collagen-based dressings demonstrated the highest hemostyptic properties with lowest adverse reactions whereas gauze did not induce high coagulation activation but rather activated leukocytes and complement.

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