Gene therapy targeting FVIII, FIX for haemophilia treatment

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Gene Therapy ◽  
Laboratory Tests ◽  
Laboratory Research ◽  
Pharmaceutical Companies ◽  
Pharmacological Properties ◽  
Clinical Use ◽  
Laboratory Studies ◽  
Regulatory Bodies ◽  
Ongoing Monitoring

Treatment for haemophilia is shifting away from standard factor replacement therapy and toward genetic repair or rebalancing, as well as overall haemostasis equilibrium. Some of these newer drugs may not have specific testing available to determine their haemostasis effects. The effects of gene therapy FVIII or FIX in vivo are under investigation, and it is expected to vary between people; nonetheless, ongoing monitoring of FVIII or FIX activity will be required. The rapid regulatory approval and adoption of emicizumab into routine clinical use surprised many haemostasis labs. Because of the challenges of monitoring patients on emicizumab, laboratories with expertise in designing alternative tests are most suited to do so.Future drugs with similar pharmacological properties to current treatments will not have a similar influence on laboratory tests. Before putting new pharmaceuticals into clinical use, pharmaceutical companies must do extensive laboratory research, and regulatory bodies must ensure that adequate laboratory studies have been completed and are available in the literature.

LABORATORY RESEARCH RESULTS OF ONION SEPARATION ON A BAR ELEVATOR WITH AN ADJUSTABLE TILT ANGLE

2020 ◽  
Keyword(s):  
Quality Indicators ◽  
Laboratory Tests ◽  
Separation Process ◽  
Laboratory Research ◽  
Laboratory Studies ◽  
Blade Angle ◽  
Quality Performance ◽  
Root Crops ◽  
Optimal Values ◽  
Translational Speed

Existing machines for harvesting root crops and onions do not provide qualitative indicators of root crops pile separation, which leads to a violation of agrotechnical requirements when harvesting them [1, 2]. It is necessary to search for new solutions to increase the quality indicators of root crop separation, namely to increase the completeness of separation and reduce damage. The article presents the design of the onion set harvesting machine, equipped with a bar elevator with an asymmetric arrangement of shakers. We described the methodology and results of laboratory studies to determine the quality indicators of heap onion sets separation on an experimental bar elevator. The results of laboratory tests of the onion set harvesting machine equipped with a bar elevator with an adjustable blade angle showed a high-quality performance of separation process at optimal values of parameters: translational speed of the bar elevator blade vEL = 1.55 ... 1.68 m s, the supply of onions heap Qb?- 19.7 ... 27.1 kg s and inclination angle of the blade bar elevator is in the range аг= 15.1... 21.9 degrees. The use of a bar elevator with an adjustable angle of inclination of the blade allows to increase the completeness of onion sets separation by 20%, and reduce damage to the bulbs by 11%.

Degradation of shaley limestone riprapAn earlier version of this paper was presented at the Canadian Geotechnical Conference in September 2003.

2007 ◽  
Vol 44 (11) ◽  
pp. 1265-1272 ◽  
Author(s):  
James Graham ◽  
Kate Franklin ◽  
Marolo Alfaro ◽  
Joel Wortley
Keyword(s):  
Laboratory Tests ◽  
Water Retention ◽  
Field Studies ◽  
Laboratory Research ◽  
Index Test ◽  
Laboratory Studies ◽  
Freezing And Thawing ◽  
Northern Canada

This paper describes field and laboratory research on limestone riprap at a water retention dyke in northern Canada. Field studies over a period of 5 years showed that weathering had reduced the size of some of the riprap, and hence the protection offered to the dyke. Laboratory tests, including the Iowa pore index test, demonstrate the capacity of the riprap to resist deterioration caused by freezing and thawing. The field and laboratory studies have been complemented by demand calculations.

scholarly journals Application and Selection of the Reagent to Neutralize Hydrogen Sulfide and Light Methyl-, Ethyl- Mercaptans in Oil

2020 ◽  
Vol 10 (6) ◽  
pp. 7042-7048
Keyword(s):  
Hydrogen Sulfide ◽  
Standard Method ◽  
Laboratory Tests ◽  
Laboratory Research ◽  
Methyl Ethyl ◽  
Laboratory Studies ◽  
Heating Oil ◽  
Two Stages ◽  
Selection Of ◽  
Pilot Tests

The choice of an effective neutralizer for a particular field is made on the basis of laboratory studies and pilot tests. A number of laboratory tests were conducted to select a hydrogen sulfide neutralizer for oil at the loading point of the Borodino field. The studies were carried out according to the standard method of the “bottle roll test” at 45°С with various amounts of the reagent-neutralizer by bubbling oil and reagents. Laboratory tests for the selection of effective reagents-neutralizers were carried out by modeling the process of collecting and preparing oil at the loading point of the Borodino field in two stages. The results of laboratory research allowed us to choose the most optimal neutralizer, set its flow rate, and temperature of oil heating. In addition, t influence of the place where the reagent - neutralizer is introduced into degassed oil is studied. The laboratory tests made it possible to select the best neutralizer Desoulfon-SNPCH-1200, to determine its minimum specific consumption and the temperature of heating oil. The application of this reagent-neutralizer will allow doing the effective oil preparation at the loading point of the Borodino field. The amount of Desoulfon-SNPCH-1200 needed to neutralize the mercaptans depends on their content in oil and the required degree of reduction.

scholarly journals Features of mechanical jaundice course caused by complications of bile disease

2020 ◽  
Vol 179 (3) ◽  
pp. 48-57 ◽  
Author(s):  
V. E. Fedorov ◽  
B. S. Haritonov ◽  
V. V. Masljakov ◽  
O. E. Logvina ◽  
M. A. Naryzhnaja
Keyword(s):  
Laboratory Tests ◽  
Clinical Symptoms ◽  
Laboratory Research ◽  
Infusion Therapy ◽  
Laboratory Studies ◽  
Biochemical Tests ◽  
Biliary Decompression ◽  
Extrahepatic Cholestasis ◽  
Complications Of Cholelithiasis ◽  
Specific Symptoms

The OBJECTIVE was improving the results of diagnostics and assessment of the severity of patients with mechanical jaundice (MJ) at various stages of its development.METHODS AND MATERIALS. The basis of clinical and laboratory research was the data of 537 patients who were admitted during the period from 2010 to 2019. Principles of separation at the stage of the course of mechanical jaundice of non-tumor Genesis.RESULTS. Analysis of clinical and laboratory studies showed characteristic signs of various complications of cholelithiasis, accompanied by mechanical jaundice. Then, on this basis, specific symptoms characteristic of each stage of mechanical jaundice of non-tumor Genesis were determined.CONCLUSION. The course of mechanical jaundice, which develops with complications of cholelithiasis, has a phase-stage character, beginning with extrahepatic cholestasis, then-joining hepatocytolysis and ending with cholangitis. Initially, cholestasis and cytolysis are functional, which is confirmed by biochemical tests, so these processes are labile and reversible. This makes it possible to effectively use biliary decompression methods and infusion therapy with detoxification during treatment. Cholangitis is characterized by destructive morphological manifestations, so it is verified by specific clinical symptoms and laboratory tests characteristic of inflammatory-septic reactions and progresses to sepsis. Differentiation of stages of mechanical jaundice allows to personify surgical and conservative treatment of such patients.

scholarly journals Anti-AAV Antibodies in AAV Gene Therapy: Current Challenges and Possible Solutions

2021 ◽  
Vol 12 ◽  
Author(s):  
Thomas Weber
Keyword(s):  
Clinical Trial ◽  
Gene Therapy ◽  
Gene Transfer ◽  
Therapeutic Efficacy ◽  
Clinical Use ◽  
Therapeutic Gene ◽  
Adeno Associated Virus ◽  
The Us ◽  
Delivery Platform

Adeno-associated virus (AAV) vector-based gene therapy is currently the only in vivo gene therapy approved in the US and Europe. The recent tragic death of three children in a clinical trial to treat X-Linked Myotubular Myopathy by delivering myotubularin with an AAV8 vector notwithstanding, AAV remains a highly promising therapeutic gene delivery platform. But the successful use of AAV vectors to treat an increasing number of diseases also makes establishing protocols to determine therapeutically relevant titers of pre-existing anti-AAV antibodies and approaches to deplete those antibodies more urgent than ever. In this mini review, I will briefly discuss (i) our knowledge regarding the prevalence of anti-AAV antibodies, (ii) the challenges to measure those antibodies by methods that are most predictive of their influence on therapeutic efficacy of AAV gene transfer, and (iii) approaches to overcome the formidable hurdle that anti-AAV antibodies pose to the successful clinical use of AAV gene therapy.

Critical limb ischaemia in diabetes: definition, assessment, prognosis

VASA ◽  
2001 ◽  
Vol 30 (Supplement 58) ◽  
pp. 21-27
Author(s):  
Luther
Keyword(s):  
Diabetic Foot ◽  
Laboratory Tests ◽  
Critical Limb Ischaemia ◽  
Limb Ischaemia ◽  
Clinical Use ◽  
Arterial Reconstruction ◽  
Arterial Circulation ◽  
Diabetic Foot Disease ◽  
Foot Disease ◽  
Fontaine Classification

In diabetic foot disease, critical limb ischaemia (CLI) cannot be precisely described using established definitions. For clinical use, the Fontaine classification complemented with any objective verification of a reduced arterial circulation is sufficient for decision making. For scientific purposes, objective measurement criteria should be reported. Assessment of CLI should rely on the physical examination of the limb arteries, complemented by laboratory tests like the shape of the PVR curve at ankle or toe levels, and arteriography. The prognosis of CLI in diabetic foot disease depends on the success of arterial reconstruction. The best prognosis for the patients is with a preserved limb. Reconstructive surgery is the best choice for the majority of patients.

Scintigraphic Detection of Experimental Myocardial Infarction with 99mTc-2,3-Dimercaptosuccinic Acid

1984 ◽  
Vol 23 (06) ◽  
pp. 317-319
Author(s):  
J. Novák ◽  
Y. Mazurová ◽  
J. Kubíček ◽  
J. Yižd’a ◽  
P. Kafka ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Intravenous Administration ◽  
Experimental Myocardial Infarction ◽  
Myocardial Infarctions ◽  
Clinical Use ◽  
Scintigraphic Imaging ◽  
Tissue Samples ◽  
Scintigraphic Finding

SummaryAcute myocardial infarctions were produced by ligature of the left frontal descending coronary artery in 9 dogs. The possibility of scintigraphic imaging with 99mTc-DMSA 4 hrs after intravenous administration was studied. The infarctions were 4, 24 and 48 hrs old. The in vivo scan was positive in only one dog with a 4-hr old infarction. The in vivo scans were confirmed by the analysis of the radioactivity in tissue samples. The accumulation of the radiopharmaceutical increased slightly in 48-hr old lesions; however, this increase was not sufficient for a positive scintigraphic finding. Thus, we do not recommend 99mTc-DMSA for clinical use in acute lesions.

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.

Toxicity of Heparinoids, with Special Reference to the Precipitation of Fibrinogen

1964 ◽  
Vol 12 (01) ◽  
pp. 232-261 ◽  
Author(s):  
S Sasaki ◽  
T Takemoto ◽  
S Oka
Keyword(s):  
Molecular Weight ◽  
Dextran Sulfate ◽  
Anticoagulant Activity ◽  
Molecular Structures ◽  
Severe Reaction ◽  
Clinical Use ◽  
Molecular Weights ◽  
Close Relationship

SummaryTo demonstrate whether the intravascular precipitation of fibrinogen is responsible for the toxicity of heparinoid, the relation between the toxicity of heparinoid in vivo and the precipitation of fibrinogen in vitro was investigated, using dextran sulfate of various molecular weights and various heparinoids.1. There are close relationships between the molecular weight of dextran sulfate, its toxicity, and the quantity of fibrinogen precipitated.2. The close relationship between the toxicity and the precipitation of fibrinogen found for dextran sulfate holds good for other heparinoids regardless of their molecular structures.3. Histological findings suggest strongly that the pathological changes produced with dextran sulfate are caused primarily by the intravascular precipitates with occlusion of the capillaries.From these facts, it is concluded that the precipitates of fibrinogen with heparinoid may be the cause or at least the major cause of the toxicity of heparinoid.4. The most suitable molecular weight of dextran sulfate for clinical use was found to be 5,300 ~ 6,700, from the maximum value of the product (LD50 · Anticoagulant activity). This product (LD50 · Anticoagulant activity) can be employed generally to assess the comparative merits of various heparinoids.5. Clinical use of the dextran sulfate prepared on this basis gave satisfactory results. No severe reaction was observed. However, two delayed reactions, alopecia and thrombocytopenia, were observed. These two reactions seem to come from the cause other than intravascular precipitation.

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.

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