377 One year double-blind immunotherapy (IT) trial with mPEG-modified (mPEG) and the corresponding unmodified (der. p.) mite allergen preparations in adult mite asthmatics. II. In vitro results

The concept of developing mRNA as vaccine platform evolved over the last decades. mRNA uses host cells for antigen production, can induce B and T cell responses and does not rely on unwanted antigens that may interfere with booster doses like vector vaccines. Unmodified mRNA (uRNA) may be highly reactogenic; modification results not only in improved tolerability but also increases purity and potency. While self-amplifying mRNA (saRNA) leads to higher antigen expression, such constructs are much larger, and this may reduce stability. mRNA vaccines need to be formulated in a way that allows cell entry, e.g., by using carefully designed lipid nanoparticles (LNP). As response to the COVID-19 pandemic, mRNA vaccines were developed in less than one year from receiving the genetic code to licensure. The 2 marketed and modRNA products widely used today (162b2, Pfizer/Biontech; mRNA-1273, Moderna) differ in vitro in their ability to induce a CD8 T cell response. The development of a third vaccine, based in uRNA, was recently stopped. Both licensed modRNA vaccines have an acceptable reactogenicity and safety profile, a protection rate of ≥94% in large double-blind-randomized studies in adults and children ≥12-years of age with a vaccine efficacy against symptomatic disease of >90% in the 6-month follow-up period.

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Effects of the Tibetan herbal preparation PADMA 28 on blood lipids and lipid oxidisability in subjects with mild hypercholesterolaemia

VASA ◽

10.1024/0301-1526.34.1.11 ◽

2005 ◽

Vol 34 (1) ◽

pp. 11-17 ◽

Cited By ~ 12

Author(s):

Brunner-La Rocca ◽

Schindler ◽

Schlumpf ◽

Saller ◽

Suter

Keyword(s):

Endothelial Dysfunction ◽

Blood Lipids ◽

Ex Vivo ◽

Hdl Cholesterol ◽

Blood Lipid ◽

Tibetan Medicine ◽

Double Blind ◽

Intraarterial Infusion ◽

Padma 28

Background: Previous studies showed an anti-atherosclerotic effect of PADMA 28, an herbal formula based on Tibetan medicine. As the mechanisms of action are not fully understood, we investigated whether PADMA 28 may lower blood lipids and lipid oxidisability, and affect early endothelial dysfunction. Patients and methods: Sixty otherwise healthy subjects with total cholesterol ≥5.2 mmol/l and < 8.0 mmol/l were randomly assigned to placebo or PADMA 28, 3 x 2 capsules daily, for 4 weeks (double-blind). Blood lipids (total, LDL-, and HDL-cholesterol, triglycerides, Apo-lipoprotein A1 and B) and ex vivo lipid oxidisability were measured before and after treatment. In a subset of 24 subjects, endothelial function was assessed using venous occlusion plethysmography with intraarterial infusion of acetylcholine. Isolated LDL and plasma both untreated and pre-treated with PADMA 28 extract were oxidised by the radical generator AAPH. Conjugated diene formation was measured at 245 nm. Results: Blood lipids did not change during the study in both groups. In contrast to previous reports in mild hypercholesterolaemia, no endothelial dysfunction was seen and, consequently, was not influenced by therapy. Ex vivo blood lipid oxidisability was significantly reduced with PADMA 28 (area under curve: 5.29 ± 1.62 to 4.99 ± 1.46, p = 0.01), and remained unchanged in the placebo group (5.33 ± 1.88 to 5.18 ± 1.78, p > 0.1). This effect persisted one week after cessation of medication. In vitro experiments confirmed the prevention of lipid peroxidation in the presence of PADMA 28 extracts. Persistent protection was also seen for LDL isolated from PADMA 28-pretreated blood after being subjected to rigorous purification. Conclusions: This study suggests that the inhibition of blood lipid oxidisability by PADMA 28 may play a role in its anti-atherosclerotic effect.

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The d-Enantiomer Form of Indobufen Totally Accounts for the Anti-Cyclooxygenase and Antiplatelet Activity Ex Vivo and for the Increase in Bleeding Time by Indobufen in Man

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648422 ◽

1992 ◽

Vol 67 (02) ◽

pp. 258-263 ◽

Cited By ~ 12

Author(s):

Raffaele De Caterina ◽

Rosa Sicari ◽

An Yan ◽

Walter Bernini ◽

Daniela Giannessi ◽

...

Keyword(s):

Arachidonic Acid ◽

Platelet Aggregation ◽

Plasma Levels ◽

Bleeding Time ◽

Ex Vivo ◽

Random Sequence ◽

Antiplatelet Agent ◽

Antiplatelet Drug ◽

Double Blind

SummaryIndobufen is an antiplatelet drug able to inhibit thromboxane production and cyclooxygenase-dependent platelet aggregation by a reversible inhibition of cyclooxygenase. Indobufen exists in two enantiomeric forms, of which only d-indobufen is active in vitro in inhibiting cyclooxygenase. In order to verify that also inhibition of platelet function is totally accounted for by d-indobufen, ten patients with proven coronary artery disease (8 male, 2 female, age, mean ± S.D., 58.7 ± 7.5 years) were given, in random sequence, both 100 mg d-indobufen and 200 mg dl-indobufen as single administrations in a double-blind crossover design study with a washout period between treatments of 72 h. In all patients thromboxane (TX) B2 generation after spontaneous clotting (at 0, 1, 2, 4, 6, 8, 12, 24 h), drug plasma levels (at the same times), platelet aggregation in response to ADP, adrenaline, arachidonic acid, collagen, PAF, and bleeding time (at 0, 2, 12 h) were evaluated after each treatment. Both treatments determined peak inhibition of TXB2 production at 2 h from administration, with no statistical difference between the two treatments (97 ±3% for both treatments). At 12 h inhibition was 87 ± 6% for d-indobufen and 88 ± 6% for dl-indobufen (p = NS). Inhibition of TXB2 production correlated significantly with plasma levels of the drugs. Maximum inhibitory effect on aggregation was seen in response to collagen 1.5 pg/ml (63 ± 44% for d-indobufen and 81 ± 22% for dl-indobufen) and arachidonic acid 0.5-2 mM (78 ± 34% for d-indobufen and 88 ± 24% for dl-indobufen) at 2 h after each administration. An effect of both treatments on platelet aggregation after 12 h was present only for adrenaline 2 μM (55 ± 41% for d-indobufen and 37 ± 54% for dl-indobufen), collagen 1.5 pg/ml (69 ± 30% for d-indobufen and 51 ± 61% for dl-indobufen), arachidonic acid 0.5-2 mM (56 ± 48% for d-indobufen and 35 ± 49% for dl-indobufen). The extent of inhibition of TX production and the extent of residual platelet aggregation were never significantly different between treatments. Bleeding time prolongation was similar in the two treatment groups without showing a pronounced and long lasting effect (from 7.0 ± 2.0 min to 10.0 ± 3.0 min at 2 h and 8.0 ± 2.0 min at 12 h for d-indobufen; from 6.0 ±1.0 min to 8.5 ± 2.0 min at 2 h and 8.0 ± 1.0 min at 12 h for dl-indobufen). These results demonstrate that the biological activity of dl-indobufen as an antiplatelet agent in vivo is totally accounted for by d-indobufen.

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The Effect of Warfarin Sodium on the Duration of Platelet Aggregation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1655087 ◽

1967 ◽

Vol 18 (03/04) ◽

pp. 766-778 ◽

Cited By ~ 2

Author(s):

H. J Knieriem ◽

A. B Chandler

Keyword(s):

Platelet Count ◽

Placebo Group ◽

Platelet Aggregation ◽

Prothrombin Time ◽

Platelet Rich Plasma ◽

Healthy Adults ◽

Double Blind Study ◽

Double Blind ◽

Warfarin Sodium

SummaryThe effect of the administration of warfarin sodium (Coumadin®) on the duration of platelet aggregation in vitro was studied. Coumadin was given for 4 consecutive days to 10 healthy adults who were followed over a period of 9 days. The duration of adenosine diphosphate-induced platelet aggregation in platelet-rich plasma, the prothrombin time, and the platelet count of platelet-rich plasma were measured. Four other healthy adults received placebos and participated in a double-blind study with those receiving Coumadin.Although administration of Coumadin caused a prolongation of the prothrombin time to 2 or 21/2 times the normal value, a decrease in the duration of platelet aggregation was not observed. In most individuals who received Coumadin an increase in the duration of platelet aggregation occurred. The effect of Coumadin on platelet aggregation was not consistently related to the prothrombin time or to the platelet count. In the placebo group there was a distinct relation between the duration of platelet aggregation and the platelet count in platelet-rich plasma.The mean increase in the duration of platelet aggregation when compared to the control value before medication with Coumadin was 37.7%. In the placebo group there was a mean increase of 8.4%. The difference between the two groups is significant (p <0.001). Increased duration of platelet aggregation also occurred in two individuals who received Coumadin over a period of 10 and 16 days respectively.

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Effects of Ticlopidine of Platelet Function in Men with Stable Angina Pectoris

Thrombosis and Haemostasis ◽

10.1055/s-0038-1660138 ◽

1985 ◽

Vol 54 (04) ◽

pp. 808-812 ◽

Cited By ~ 7

Author(s):

Ulf Berglund ◽

Henning von Schenck ◽

Lars Wallentin

Keyword(s):

Platelet Aggregation ◽

Angina Pectoris ◽

Platelet Function ◽

Plasma Levels ◽

Platelet Reactivity ◽

Inhibitory Effect ◽

Controlled Study ◽

Double Blind ◽

Platelet Factor

SummaryThe effects of ticlopidine (T) (500 mg daily) on platelet function were investigated in a double-blind placebo-controlled study in 38 middle-aged men with stable incapacitating angina pectoris. The in vitro platelet reactivity to aggregating agents, the platelet sensitivity to prostacyclin and the plasma levels of platelet specific proteins and fibrinogen were determined before and after 4 and 8 weeks of treatment. T exerted a potent inhibitory effect on ADP- and collagen-induced platelet aggregation. The effect of T was proportional to the pretreatment reactivity to ADP and collagen. The inhibitory effect of T on the epinephrine response was less pronounced. The plasma levels of beta-thromboglobulin, platelet factor 4 and fibrinogen were not influenced by T. The platelet inhibition of prostacyclin was potentiated by T, and it was demonstrated that T and prostacyclin had synergistic inhibitory effects on platelet aggregation.

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Inhibition of Spontaneous Platelet Aggregation by Sulfinpyrazone

Thrombosis and Haemostasis ◽

10.1055/s-0038-1666900 ◽

1979 ◽

Vol 42 (02) ◽

pp. 621-625 ◽

Cited By ~ 1

Author(s):

G G Nenci ◽

G Agnelli ◽

M Berrettini ◽

P Parise ◽

E Ballatori

Keyword(s):

Platelet Aggregation ◽

Crossover Study ◽

Double Blind ◽

Platelet Aggregability ◽

Initiation Of Therapy ◽

Spontaneous Platelet Aggregation ◽

Blind Crossover Study ◽

Double Blind Crossover Study

SummaryIn a randomized double-blind crossover study in 16 patients with enhanced in vitro spontaneous platelet aggregation, sulfinpyrazone proved to be effective in normalizing platelet aggregability within 4 days after initiation of therapy.

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310. A Single Skin Contact with Toluene Diiscoyante (Tdi) Causes a One-Year Persistence of Airway Sensitization, Demonstrable in Vivo and in Vitro

10.3320/1.2764985 ◽

1999 ◽

Author(s):

U. Bickis ◽

K. Nakatsu

Keyword(s):

Skin Contact ◽

One Year

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IL-6 Receptor Blockade Increases Circulating Adiponectin Levels in People with Obesity: An Explanatory Analysis

Metabolites ◽

10.3390/metabo11020079 ◽

2021 ◽

Vol 11 (2) ◽

pp. 79

Author(s):

Stephan Wueest ◽

Eleonora Seelig ◽

Katharina Timper ◽

Mark P. Lyngbaek ◽

Kristian Karstoft ◽

...

Keyword(s):

Exercise Training ◽

Human Subjects ◽

Receptor Blockade ◽

Model Assessment ◽

Serum Samples ◽

Double Blind ◽

Double Blind Clinical Trial ◽

Homeostatic Model Assessment ◽

Obese Human

Human obesity is associated with decreased circulating adiponectin and elevated leptin levels. In vitro experiments and studies in high fat diet (HFD)-fed mice suggest that interleukin-6 (IL-6) may regulate adiponectin and leptin release from white adipose tissue (WAT). Herein, we aimed to investigate whether IL-6 receptor blockade affects the levels of circulating adiponectin and leptin in obese human individuals. To this end, serum samples collected during a multicenter, double-blind clinical trial were analyzed. In the latter study, obese human subjects with or without type 2 diabetes were randomly assigned to recurrent placebo or intravenous tocilizumab (an IL-6 receptor antibody) administration during a 12-week exercise training intervention. Twelve weeks of tocilizumab administration (in combination with exercise training) trend wise enhanced the decrease in circulating leptin levels (−2.7 ± 8.2% in the placebo vs. −20.6 ± 5.6% in tocilizumab, p = 0.08) and significantly enhanced the increase in circulating adiponectin (3.4 ± 3.7% in the placebo vs. 27.0 ± 6.6% in tocilizumab, p = 0.01). In addition, circulating adiponectin levels were negatively correlated with the homeostatic model assessment of insulin resistance (HOMA-IR), indicating that increased adiponectin levels positively affect insulin sensitivity in people with obesity. In conclusion, IL-6 receptor blockade increases circulating adiponectin levels in people with obesity.

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Telomere Length in Norway Spruce during Somatic Embryogenesis and Cryopreservation

Plants ◽

10.3390/plants10020416 ◽

2021 ◽

Vol 10 (2) ◽

pp. 416

Author(s):

Tuija Aronen ◽

Susanna Virta ◽

Saila Varis

Keyword(s):

Somatic Embryogenesis ◽

Telomere Length ◽

Norway Spruce ◽

Genotypic Variation ◽

Production Capacity ◽

Stress Factors ◽

Embryo Production ◽

One Year ◽

Plant Telomeres

Telomeres i.e., termini of the eukaryotic chromosomes protect chromosomes during DNA replication. Shortening of telomeres, either due to stress or ageing is related to replicative cellular senescence. There is little information on the effect of biotechnological methods, such as tissue culture via somatic embryogenesis (SE) or cryopreservation on plant telomeres, even if these techniques are widely applied. The aim of the present study was to examine telomeres of Norway spruce (Picea abies (L.) Karst.) during SE initiation, proliferation, embryo maturation, and cryopreservation to reveal potential ageing or stress-related effects that could explain variation observed at SE process. Altogether, 33 genotypes from 25 families were studied. SE initiation containing several stress factors cause telomere shortening in Norway spruce. Following initiation, the telomere length of the embryogenic tissues (ETs) and embryos produced remains unchanged up to one year of culture, with remarkable genotypic variation. Being prolonged in vitro culture can, however, shorten the telomeres and should be avoided. This is achieved by successful cryopreservation treatment preserving telomere length. Somatic embryo production capacity of the ETs was observed to vary a lot not only among the genotypes, but also from one timepoint to another. No connection between embryo production and telomere length was found, so this variation remains unexplained.

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