scholarly journals Effects of Topically Applied Betulinic Acid and NVX-207 on Melanocytic Tumors in 18 Horses

Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3250
Author(s):  
Lisa A. Weber ◽  
Julien Delarocque ◽  
Karsten Feige ◽  
Manfred Kietzmann ◽  
Jutta Kalbitz ◽  
...  
Keyword(s):  
Betulinic Acid ◽  
Early Stage ◽  
Statistical Significance ◽  
Treatment Protocol ◽  
Controlled Study ◽  
Double Blind ◽  
Current Form ◽  
Melanocytic Tumors ◽  
High Concentrations

The naturally occurring betulinic acid (BA) and its derivative NVX-207 induce apoptosis in equine melanoma cells in vitro. After topical application, high concentrations of the substances can be reached in healthy equine skin. With the aim to investigate the effect and safety of topically applied BA and NVX-207 in horses with melanocytic tumors, the longitudinal, prospective, randomized, double-blind, placebo-controlled study protocol included eighteen Lipizzaner mares with early-stage cutaneous melanoma assigned to three groups. Melanocytic lesions were topically treated either with a placebo, 1% BA or 1% NVX-207 twice a day for 91 days. Caliper measurements, clinical examinations and blood tests were performed to assess the effects and safety of the medication. The topical treatment was convenient and safe. The volumes of tumors treated with BA were significantly reduced over time as compared to tumors treated with the placebo from day 80 of the study. Although treatment with NVX-207 seemed to decrease tumor volume, these results did not reach statistical significance. The findings must be regarded as preliminary due to the limited group size and need to be replicated in a larger cohort with modified pharmaceutical test formulations. Accordingly, the treatment protocol cannot yet be recommended in its current form.

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

1985 ◽  
Vol 54 (04) ◽  
pp. 808-812 ◽  
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.

Application of the EYTEX™ System to the Evaluation of Cosmetic Products and their Ingredients

1992 ◽  
Vol 20 (1) ◽  
pp. 146-163
Author(s):  
Francis H. Kruszewski ◽  
Laura H. Hearn ◽  
Kyle T. Smith ◽  
Janice J. Teal ◽  
Virginia C. Gordon ◽  
...  
Keyword(s):  
Double Blind ◽  
Eye Irritation ◽  
Ocular Irritation ◽  
Rabbit Eye ◽  
Wide Range ◽  
High Concentrations ◽  
Alkaline Membrane ◽  
Positive Agreement

465 cosmetic product formulations and raw ingredients were evaluated with the EYTEX™ system to determine the potential of this in vitro alternative for identifying eye irritation potential. The EYTEX™ system is a non-animal, biochemical procedure developed by Ropak Laboratories, Irvine, CA, that was designed to approximate the Draize rabbit eye irritation assay for the evaluation of ocular irritation. Avon Products Inc. provided all the test samples, which included over 30 different product types and represented a wide range of eye irritancy. All the EYTEX™ protocols available at the time of this study were used. Samples were evaluated double-blind with both the membrane partition assay (MPA) and the rapid membrane assay (RMA). When appropriate, the standard assay (STD) and the alkaline membrane assay (AMA) were used, as well as specific, documented protocol modifications. EYTEX™ results were correlated with rabbit eye irritation data which was obtained from the historical records of Avon Products Inc. A positive agreement of EYTEX™ results with the in vivo assay was demonstrated by an overall concordance of 80%. The assay error was 20%, of which 18% was due to an overestimation of sample irritancy (false positives) and 2% was attributed to underestimation (false negatives). Overestimation error in this study was due in part to the inability of the protocols to accurately classify test samples with very low irritation potential. Underestimation of sample irritancy was generally associated with ethoxylated materials and high concentrations of specific types of surfactants. 100% sensitivity and 85% predictability were described by the data, indicating the efficiency of EYTEX™ in identifying known irritants. A specificity rate of 39% showed the EYTEX™ assay to be weak in discerning non-irritants. However, the EYTEX™ protocols used in this study were not designed to identify non-irritants. A compatibility rate of 99% proved the effectiveness of the EYTEX™ assay in accommodating a diversity of product types. The EYTEX™ system protocols, when used appropriately, can provide a conservative means of assessing the irritant potential of most cosmetic formulations and their ingredients.

scholarly journals Oral Intake of Hydrangea serrata (Thunb.) Ser. Leaves Extract Improves Wrinkles, Hydration, Elasticity, Texture, and Roughness in Human Skin: A Randomized, Double-Blind, Placebo-Controlled Study

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1588
Author(s):  
Da-Bin Myung ◽  
Jeong-Hun Lee ◽  
Hee-Soo Han ◽  
Kwang-Young Lee ◽  
Hye Shin Ahn ◽  
...  
Keyword(s):  
Human Skin ◽  
Elastic Recovery ◽  
Controlled Trial ◽  
Water Extract ◽  
Hot Water ◽  
Controlled Study ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Skin Wrinkles

Previously, we reported that the hot water extract of Hydrangea serrata leaves (WHS) and its active component, hydrangenol, possess in vitro and in vivo effects on skin wrinkles and moisturization. We conducted a randomized, double-blind, placebo-controlled trial to clinically evaluate the effect of WHS on human skin. Participants (n = 151) were randomly assigned to receive either WHS 300 mg, WHS 600 mg, or placebo, once daily for 12 weeks. Skin wrinkle, hydration, elasticity, texture, and roughness parameters were assessed at baseline and after 4, 8, and 12 weeks. Compared to the placebo, skin wrinkles were significantly reduced in both WHS groups after 8 and 12 weeks. In both WHS groups, five parameters (R1–R5) of skin wrinkles significantly improved and skin hydration was significantly enhanced when compared to the placebo group after 12 weeks. Compared with the placebo, three parameters of skin elasticity, including overall elasticity (R2), net elasticity (R5), and ratio of elastic recovery to total deformation (R7), improved after 12 weeks of oral WHS (600 mg) administration. Changes in skin texture and roughness were significantly reduced in both WHS groups. No WHS-related adverse reactions were reported. Hence, WHS could be used as a health supplement for skin anti-aging.

scholarly journals Probiotics: on-going research on atopic individuals

2002 ◽  
Vol 88 (S1) ◽  
pp. s19-s27 ◽  
Author(s):  
K. Laiho ◽  
U. Hoppu ◽  
A. C. Ouwehand ◽  
S. Salminen ◽  
E. Isolauri
Keyword(s):  
At Risk ◽  
Atopic Eczema ◽  
Atopic Disease ◽  
Interleukin 4 ◽  
Controlled Study ◽  
Future Research ◽  
Gut Microflora ◽  
Double Blind ◽  
Ongoing Research

The challenge for the modern health care system is to fight against the increasing prevalence of atopic disease. The introduction of scientifically composed probiotic functional foods for prophylactic or therapeutic purposes could be one solution. Probiotics are live microbial food supplements or components of bacteria which have beneficial effects on human health. Specific strains have been demonstrated to exert powerful anti-pathogenic, anti-inflammatory and anti-allergic effects. The hygiene hypothesis suggests that atopic disease may arise from a lack of counterbalancing microbial exposure at an early age. The initial compositional development of the gut microflora is considered a key determinant of the development of both the immune responder phenotype and normal gut barrier functions. The regulatory role of probiotics in human allergic disease was first emphasised in the demonstration of a suppressive effect on lymphocyte proliferation and interleukin-4 generationin vitro. Subsequently, a significant improvement in the clinical course of atopic eczema was reported in infants given a probiotic-supplemented diet. The potential of probiotics to reduce the risk of atopic disease has recently been demonstrated in a double-blind, placebo-controlled study: probiotics administered pre- and postnatally for 6 months to at-risk subjects reduced the prevalence of atopic eczema to half of that observed in infants receiving placebo. Ongoing research is directed towards the development of novel techniques to characterise the gut microflora. Future research will clarify the mechanisms to control specific physiological processes in the evolution of atopic disease in at-risk populations or in the management of allergic diseases.

scholarly journals Efficacy of an Oral Rehydration Solution Enriched with Lactobacillus reuteri DSM 17938 and Zinc in the Management of Acute Diarrhoea in Infants: A Randomized, Double-Blind, Placebo-Controlled Trial

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1189 ◽  
Author(s):  
Maria Maragkoudaki ◽  
George Chouliaras ◽  
Antonia Moutafi ◽  
Athanasios Thomas ◽  
Archodoula Orfanakou ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Lactobacillus Reuteri ◽  
Oral Rehydration Solution ◽  
Statistical Significance ◽  
Acute Diarrhoea ◽  
Controlled Study ◽  
Double Blind ◽  
Oral Rehydration ◽  
Number Of Patients ◽  
Rehydration Solution

The efficacy of oral rehydration solution (ORS) enriched with Lactobacillus reuteri DSM 17938 and zinc in infants with acute gastroenteritis, is poorly defined. The aim of this double-blind, randomized, placebo-controlled study, was to assess the efficacy of an ORS enriched with Lactobacillus reuteri DSM 17938 and zinc (ORS+Lr&Z) in well-nourished, non-hospitalized infants with acute diarrhoea. Fifty one infants with acute diarrhoea were randomly assigned to receive either ORS+Lr&Z (28 infants, mean ± SD age 1.7 ± 0.7 years, 21 males), or standard ORS (ORS−Lr&Z; 23 infants, mean ± SD age 1.8 ± 0.7 years, 16 males). Stools volume and consistency were recorded pre- and posttreatment using the Amsterdam Infant Stool Scale and were compared between the two groups, as well as lost work/day care days, drug administration and need for hospitalization. Both groups showed reduction in the severity of diarrhoea on day two (p < 0.001) while, all outcomes showed a trend to be better in the ORS+Lr&Z group, without reaching statistical significance, probably due to the relatively small number of patients. No adverse effects were recorded. In conclusion, both ORS were effective in managing acute diarrhoea in well-nourished, non-hospitalized infants. ORS enriched with L. reuteri DSM 17938 and zinc was well tolerated with no adverse effects.

Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers

2006 ◽  
Vol 290 (5) ◽  
pp. G942-G947 ◽  
Author(s):  
Michael Camilleri ◽  
Adil E. Bharucha ◽  
Ryuji Ueno ◽  
Duane Burton ◽  
George M. Thomforde ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Chloride Channel ◽  
Chloride Channels ◽  
Gastrointestinal Transit ◽  
Intestinal Secretion ◽  
Gastric Volume ◽  
Colonic Transit ◽  
Controlled Study ◽  
Double Blind

Chloride channels modulate gastrointestinal neuromuscular functions in vitro. Lubiprostone, a selective type 2 chloride channel (ClC-2) activator, induces intestinal secretion and has been shown to relieve constipation in clinical trials; however, the effects of lubiprostone on gastric function and whole gut transit in humans are unclear. Our aim was to compare the effects of the selective ClC-2 activator lubiprostone on maximum tolerated volume (MTV) of a meal, postprandial symptoms, gastric volumes, and gastrointestinal and colonic transit in humans. We performed a randomized, parallel-group, double-blind, placebo-controlled study evaluating the effects of lubiprostone (24 μg bid) in 30 healthy volunteers. Validated methods were used: scintigraphic gastrointestinal and colonic transit, SPECT to measure gastric volumes, and the nutrient drink (“satiation”) test to measure MTV and postprandial symptoms. Lubiprostone accelerated small bowel and colonic transit, increased fasting gastric volume, and retarded gastric emptying. MTV values were reduced compared with placebo; however, the MTV was within the normal range for healthy adults in 13 of 14 participants, and there was no significant change compared with baseline measurements. Lubiprostone had no significant effect on postprandial gastric volume or aggregate symptoms but did decrease fullness 30 min after the fully satiating meal. Thus the ClC-2 activator lubiprostone accelerates small intestinal and colonic transit, which confers potential in the treatment of constipation.

Reduced thromboembolic events with DN-101 (high-dose calcitriol) treatment of androgen-independent prostate cancer: Hypothesis for a new class of anticoagulants

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4505-4505 ◽  
Author(s):  
P. M. Venner ◽  
C. Ryan ◽  
D. P. Petrylak ◽  
G. S. Chatta ◽  
J. Ruether ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Active Form ◽  
Coagulation Cascade ◽  
Controlled Study ◽  
High Dose ◽  
Thromboembolic Events ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Androgen Independent

4505 Background: Thromboembolic events (TEs) occur at an increased rate in patients with advanced malignancies including androgen-independent prostate cancer (AIPC). DN-101, a new high-dose oral formulation of calcitriol (1,25-dihydroxycholecalciferol), is the active form of Vitamin D and the natural ligand for the nuclear receptor VDR. Calcitriol upregulates thrombomodulin, a natural anticoagulant, and downregulates tissue factor, a procoagulant both in vitro and in vivo. Further, VDR knockout mice demonstrate increased susceptibility to thrombosis. ASCENT is a double-blind, placebo-controlled study in 250 men with metastatic AIPC. Efficacy results have been previously reported (ASCO, 2005). Methods: 250 patients were randomized 1:1 to docetaxel 36 mg/m2 plus 45 μg DN-101 weekly or to the same docetaxel regimen plus placebo. In this exploratory analysis the incidence of TE (defined as deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI), cerebrovascular accident (CVA) and arterial thrombosis (AT)) in the two study groups was compared using the Fisher’s exact test. Results: There were fewer patients with serious adverse events (SAEs) in the DN-101 group than in the placebo group (27 % vs. 41%). As shown in the table , DN-101 treated patients experienced fewer TEs including fewer TE SAEs, Grade 3 or 4 TEs and all grade TEs. No imbalance in baseline use of anticoagulants was observed. Conclusions: The well-described effects of calcitriol on protein components of the coagulation cascade provide a biologic basis for the observed reduction in thromboembolic events in the DN-101 treated patients. This hypothesis should be tested prospectively in future studies of DN-101. [Table: see text] [Table: see text]

Checkmate 77T: A phase III trial of neoadjuvant nivolumab (NIVO) plus chemotherapy (chemo) followed by adjuvant nivo in resectable early-stage NSCLC.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS9076-TPS9076
Author(s):  
Tina Cascone ◽  
Mariano Provencio ◽  
Boris Sepesi ◽  
Shun Lu ◽  
Nivedita Aanur ◽  
...  
Keyword(s):  
Oral Presentation ◽  
Lung Tumor ◽  
Early Stage ◽  
Performance Status ◽  
Unmet Need ◽  
Phase Iii ◽  
Rational Approach ◽  
Controlled Study ◽  
Double Blind ◽  
Early Stage Nsclc

TPS9076 Background: Although surgery for early NSCLC is potentially curative, 5-year overall survival (OS) rates for patients with stage IIA–IIIB disease are historically < 50%, representing a population of high unmet need. Conventional neoadjuvant or adjuvant chemo provides only a 5% absolute improvement in OS at 5 years. A rational approach to improve survival in these patients is to eradicate micrometastatic disease and potentially induce anti-tumor immunity to minimize the risk of relapse with peri-operative regimens including NIVO, a fully human anti–programmed death receptor-1 antibody. Early phase trials indicate that NIVO-based regimens have the potential to deepen pathological responses and extend survival in this setting (Reuss JE et al. Poster presentation at ASCO 2019. Abstract 8524; Cascone T et al. Oral presentation at ASCO 2019. Abstract 8504; Provencio M et al. Oral presentation at WCLC 2019. Abstract OA13.05). Data from the phase 2 single-arm NADIM trial (NCT03081689) demonstrated the highly encouraging major pathological response (MPR) rate of 83% with neoadjuvant NIVO plus chemo followed by adjuvant NIVO in patients with resectable stage IIIA NSCLC (Provencio M et al. Oral presentation at WCLC 2019. Abstract OA13.05). These results require validation in a large randomized controlled study. CheckMate 77T (NCT04025879) is a phase 3, randomized, double-blind trial evaluating neoadjuvant NIVO plus chemo followed by adjuvant NIVO in resectable early stage NSCLC. Methods: Approximately 452 patients aged ≥ 18 years with resectable stage IIA–IIIB (T3N2 only) NSCLC, ECOG performance status 0–1, and available lung tumor tissue will be enrolled at 113 sites in North America, South America, Europe, Asia, and Australia. Patients with EGFR/ALK mutations, brain metastasis, prior systemic anti-cancer treatment or radiotherapy, and autoimmune disease are excluded. Patients will be randomized to receive neoadjuvant NIVO plus carboplatin- or cisplatin-based doublet chemo followed by surgery and adjuvant NIVO, or neoadjuvant placebo plus carboplatin- or cisplatin-based doublet chemo followed by surgery and adjuvant placebo. The primary endpoint is event-free survival, assessed by blinded independent central review. Secondary endpoints include OS, pathological complete response and MPR assessed by blind independent pathological review, safety and tolerability. The start date was September 2019. The estimated primary completion date is May 2023. Clinical trial information: NCT04025879.

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