scholarly journals Evaluation of Microleakage by Gas Permeability and Marginal Adaptation of MTA and Biodentine™ Apical Plugs: In Vitro Study

2017 ◽  
Vol 20 (1) ◽  
pp. 57-67
Author(s):  
Karen Brenes-Valverde DDS ◽  
Elian Conejo-Rodríguez PhD ◽  
José Roberto Vega-Baudrit PhD ◽  
Mauricio Montero-Aguilar MSc ◽  
Daniel Chavarría-Bolaños MSc, PhD
Keyword(s):  
Gas Permeability ◽  
In Vitro Study ◽  
Cylindrical Sample ◽  
In Vivo Studies ◽  
Marginal Adaptation ◽  
Nitrogen Diffusion ◽  
Human Teeth ◽  
Significant Difference

The endodontic treatment of teeth with incomplete development is always a complex task. Nowadays, biomaterials such as bioceramics offers promising clinical evidence that supports its use. However, the standardization of its use for apexification purpose still needs a deeper understanding of the materials’ behavior. The aim of this investigation was to evaluate the marginal adaptability and microleakage by gas permeability of MTA and Biodentine™ apical plugs in an in vitro model. Materials and methods: Twenty-four single rooted human teeth were selected according to previously stablished inclusion criteria. All samples were prepared obtaining standard cylindrical internal canals with a diameter of 1.3 mm. Root canals were gently rinsed using 5.25% sodium hypochlorite and EDTA 17%. The apical 3mm and remaining coronal dental structure were sectioned to obtain 10mm roots. Roots were randomly assigned to 3 different groups as follows: GROUP A: MTA (n=10), GROUP B: Biodentine™ (n=10) and Group C: Control (positive n=1, negative n=3). MTA and Biodentine™ were prepared according to manufacturer’s indications, and apical plugs of 4mm were passively placed in the correspondent teeth. All samples were stored in saline solution for 7 days at 37°C before evaluation. Samples were mounted in cylindrical sample-holders using epoxy resin. Microleakage was evaluated with an automatic permeability detector that calculates nitrogen diffusion between the material-root interphase. After microleakage evaluation, the samples were recovered and analyzed by scanning electron microscopy (SEM). Microleakage results were analyzed using Chi-square and adaptation was evaluated with a descriptive analysis. Results: None of the evaluated materials completely avoided the nitrogen microleakage (positive leakage of 10% and 20% of samples for MTA and Biodentine™ respectively); with no statistical significant difference between groups (p=0.527).  All apical plugs showed good adaptation under SEM, at 30x, 200x, 1000x and 2500x; with microscopical structures similar to previous reports. Conclusions: Both bioceramics behave similar when used as apical barriers to avoid permeability, with acceptable marginal adaptation. Further in vivo studies are needed to validate these results.  

scholarly journals Evaluation of Microleakage by Gas Permeability and Marginal Adaptation of MTA and Biodentine™ Apical Plugs: In Vitro Study

2017 ◽  
Vol 20 (1) ◽  
pp. 57-67
Author(s):  
Karen Brenes-Valverde DDS ◽  
Elian Conejo-Rodríguez PhD ◽  
José Roberto Vega-Baudrit PhD ◽  
Mauricio Montero-Aguilar MSc ◽  
Daniel Chavarría-Bolaños MSc, PhD
Keyword(s):  
Gas Permeability ◽  
In Vitro Study ◽  
Cylindrical Sample ◽  
In Vivo Studies ◽  
Marginal Adaptation ◽  
Nitrogen Diffusion ◽  
Human Teeth ◽  
Significant Difference

The endodontic treatment of teeth with incomplete development is always a complex task. Nowadays, biomaterials such as bioceramics offers promising clinical evidence that supports its use. However, the standardization of its use for apexification purpose still needs a deeper understanding of the materials’ behavior. The aim of this investigation was to evaluate the marginal adaptability and microleakage by gas permeability of MTA and Biodentine™ apical plugs in an in vitro model. Materials and methods: Twenty-four single rooted human teeth were selected according to previously stablished inclusion criteria. All samples were prepared obtaining standard cylindrical internal canals with a diameter of 1.3 mm. Root canals were gently rinsed using 5.25% sodium hypochlorite and EDTA 17%. The apical 3mm and remaining coronal dental structure were sectioned to obtain 10mm roots. Roots were randomly assigned to 3 different groups as follows: GROUP A: MTA (n=10), GROUP B: Biodentine™ (n=10) and Group C: Control (positive n=1, negative n=3). MTA and Biodentine™ were prepared according to manufacturer’s indications, and apical plugs of 4mm were passively placed in the correspondent teeth. All samples were stored in saline solution for 7 days at 37°C before evaluation. Samples were mounted in cylindrical sample-holders using epoxy resin. Microleakage was evaluated with an automatic permeability detector that calculates nitrogen diffusion between the material-root interphase. After microleakage evaluation, the samples were recovered and analyzed by scanning electron microscopy (SEM). Microleakage results were analyzed using Chi-square and adaptation was evaluated with a descriptive analysis. Results: None of the evaluated materials completely avoided the nitrogen microleakage (positive leakage of 10% and 20% of samples for MTA and Biodentine™ respectively); with no statistical significant difference between groups (p=0.527).  All apical plugs showed good adaptation under SEM, at 30x, 200x, 1000x and 2500x; with microscopical structures similar to previous reports. Conclusions: Both bioceramics behave similar when used as apical barriers to avoid permeability, with acceptable marginal adaptation. Further in vivo studies are needed to validate these results.  

scholarly journals Primary Stability of Three Different Osteotomy Techniques in Medullary Bone: An in Vitro Study

2020 ◽  
Vol 8 (1) ◽  
pp. 21 ◽  
Author(s):  
Ferdinando Attanasio ◽  
Alessandro Antonelli ◽  
Ylenia Brancaccio ◽  
Fiorella Averta ◽  
Michele Mario Figliuzzi ◽  
...  
Keyword(s):  
In Vitro Study ◽  
Primary Stability ◽  
Vitro Study ◽  
In Vivo Studies ◽  
Insertion Torque ◽  
Medullary Bone ◽  
Significant Difference ◽  
Twist Drills

Background: The aim of this in vitro study was to analyse the primary stability of 20 implants placed with Twist drills (TD) versus 20 implants placed with Summers osteotomes (SO) and 20 implants placed with B&B bone compactors (BC) in medullary bone (quality type III and type IV). Methods: The implants were placed in 10 fresh pig ribs fixed on a bench vice in order to avoid micro-movements during surgical procedures and measure recording. Peak insertion torque (PIT) and Peak removal torque (PRT) were recorded with MGT-12 digital torque gauge and ISQ was recorded through OSSTELL ISQ™ device by an independent operator. Results: Comparing our data (Tukey test p = 0.05), it was evidenced a statistically significant difference in the PIT between TD and BC groups (p = 0.01). Analysing ISQ data, there was a statistically significant difference between the TD and BC groups (p = 0.0001) and between the SO and BC groups (p = 0.014). The analysis of PRT evidenced a statistically significant difference between the TD and BC groups (p = 0.038). Conclusions: This study evidenced that bone compactor preparation can positively influence primary implant stability (PS), however further in vivo studies and a larger sample are necessary to assess the usefulness in several clinical settings.

scholarly journals The Antibacterial Efficacy of Biopure MTAD in Root Canal Contaminated with Enterococcus faecalis

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Blerim Kamberi ◽  
Donika Bajrami ◽  
Miranda Stavileci ◽  
Shuhreta Omeragiq ◽  
Fatmir Dragidella ◽  
...  
Keyword(s):  
In Vitro Study ◽  
Sodium Hypochlorite Solution ◽  
Antibacterial Efficacy ◽  
Human Teeth ◽  
Exact Test ◽  
Hypochlorite Solution ◽  
Root Canals ◽  
Significant Difference ◽  
Level Of Significance

Aim. The purpose of this in vitro study was to assess the antimicrobial efficacy of Biopure MTAD against E. faecalis in contaminated root canals. Materials and Methods. Forty-two single rooted extracted human teeth were inoculated with E. faecalis and incubated for four weeks. The samples were divided in two control and five experimental groups irrigated with 1.5% sodium hypochlorite solution (NaOCl); 3% NaOCl; BioPure MTAD; 1.5% NaOCl/17% EDTA; or 3% NaOCl/17% EDTA. After a one-week incubation, complete disinfection was confirmed by the absence of turbidity in the incubation media. Dentin shavings were taken from samples with no turbidity to verify whether E. faecalis was present in dentin tubules. Results were analyzed statistically using Fisher's exact test, with the level of significance set at . Results. Statistical analysis of the data obtained at Day 7 and after dentin shaving analysis showed that BioPure MTAD had significantly greater antibacterial activity than 1.5% NaOCl, 1.5% NaOCl/17% EDTA and 3% NaOCl/17% EDTA. No significant difference was detected between MTAD and 3% NaOCl. Conclusions. These findings suggest that BioPure MTAD possesses superior bactericidal activity compared with NaOCl and EDTA against E. faecalis.

Analysis on Homoeopathic Preparation of Asterias Rubens for Evaluating Anti Breast Cancer Cell Line using Similia Principle

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 805-808
Author(s):  
Ravikumar Raju ◽  
Teja ◽  
Sravanathi P ◽  
Muthu Babu K
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
In Vitro Study ◽  
In Vivo Studies ◽  
Asterias Rubens ◽  
Mcf 7

Breast cancer is the subsequent foremost reason of cancer death in a woman and ranks as the primary foremost reason of death in India. In its conduct, several measures and recommendation are considered. Homoeopathic medicines are one of the part of a corresponding, and another medicine is utilized for the treatment of cancer. The main purpose of the investigation is to evaluate the anticancer action of homoeopathic arrangements of Asterias rubens  on the basis of the similia principle. We directed an in vitro study using MTT assay to control the result of ultra diluted homoeopathic preparation in contradiction of two human breast glandular cancer cell lines(MCF-7 and MDA-MD- 231), frequently used for the breast cancer treatment, by testing the feasibility of breast cancer (MCF-7 and MDA-MD-231) cell line, with various attenuations of Asterias rubens  at 24 hrs. Multiple comparisons between tested reagents at different concentrations confirmed the significance of the said results. At a dilution of 1:25 6CH and 30CH potency shown superior activity on MCF-7 and no such significant changes on MDA-MD-231 at any dilutions As it fails to offer estrogen receptor(ER) Also progesterone receptor (PR) expression, and also HER2 (human epidermal development variable receptor2) so continuously a triple-negative breast cancer it will be a hostility manifestation for breast cancer with restricted medicine choices. However, further potency needs to be tested. These preliminary significant results warrant further in vitro and in vivo studies to estimate the possible of Asterias rubens  a medicine to treat breast cancer.

Use of Medium Potency Statins Is Associated with Improved Outcomes after Frontline RCHOP in Patients with Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 45-45
Author(s):  
Sushanth Gouni ◽  
Paolo Strati ◽  
Jason Westin ◽  
Loretta J. Nastoupil ◽  
Raphael E Steiner ◽  
...  
Keyword(s):  
Cell Lines ◽  
Research Funding ◽  
Response Assessment ◽  
Cholesterol Content ◽  
In Vivo Studies ◽  
High Cholesterol ◽  
Improved Outcomes ◽  
Significant Difference

Background: Pre-clinical studies show that statins may improve the efficacy of chemoimmunotherapy in patients with DLBCL, through interference with cell membrane-initiated signaling pathways. Clinical retrospective studies, however, yield conflicting data, due to heterogeneous properties of statins, including potency and hydrophilicity. Methods: This is a retrospective analysis of patients with previously untreated, advanced stage DLBCL, non-double hit, treated with frontline R-CHOP between 01/01/2000 and 09/01/2019 (data cut-off 04/15/2020) at MD Anderson Cancer Center, and for whom data regarding statin use at time of initiation of treatment were available. Lugano 2014 response criteria were applied retrospectively for response assessment. Cellular cholesterol levels were analyzed in 6 DLBCL cell lines using an Amplex red fluorometric assay. A doxorubicin (DXR)-resistant cell line was generated exposing SUDHL4 cells to escalating doses of DXR; a DXR-resistant DLBCL patient-derived xenograft (PDX) model was established through serial transplantation and exposure to DXR. Results: 271 patients were included in the analysis, 182 (67%) were older than 60 years, 134 (49%) were male, 212 (72%) had stage IV disease, and 217 (80%) had an IPI score > 3; upon pathological review, 38 (36%) cases were non-GCB type, and 18 (28%) were double-expressors; 214 (79%) were able to complete all planned 6 cycles of RCHOP. Seventy-nine (29%) patients received statins at time of initiation of chemoimmunotherapy: 15 patients received low potency statin, 51 medium and 13 high; 18 patients received hydrophilic statins and 61 lipophilic. Patients receiving statins were significantly older as compared to patients who did not (p<0.001); no other significant difference in baseline characteristics was observed when comparing the 2 groups. Overall, 265 out of 271 patients were evaluable for response, as 6 stopped treatment because of toxicity before first response assessment. Among these, ORR was 95% (252/265) and CR rate was 62% (165/265). ORR rate was identical in patients who were treated with statin and those who did not (95% both, p=1). After a median follow-up of 77 months (95% CI, 70-84 months), 119 patients progressed/died, median PFS was not reached and 6-year PFS was 57%. 6-year PFS rate according to statin intensity was: 48% (low), 72% (medium), 57% (high). PFS. 6-year PFS rate was 64% for hydrophilic and 72% for lipophilic statins. Patients treated with statins had a trend for longer PFS (p=0.06), significantly longer for patients receiving medium potency statins (p=0.04). No significant difference in PFS was observed when comparing patients treated with lipophilic statins to all others (not reached vs 84 months, p=0.22). To confirm these clinical data, in-vitro and in-vivo studies were performed. Six cell lines were tested: 4 with high cholesterol content (SUDHL4, HBL1, HT, and U2932; 5.0-8.0 µg/mg protein), and 2 with low cholesterol content (DOHH2 and OCI-LY19; 1.5-2.0 µg/mg protein); the latter showed the highest sensitivity to DXR-mediated killing. The combination of lovastatin and DXR (10nM) was tested in all 4 cell lines with high cholesterol content, resulting in more cell death than either treatment alone. Lovastatin (at the nanomolar range) resensitized DXR-resistant SUDHL4 cells to DXR. Finally, in a DXR-resistant PDX model, the combination of lovastatin and DXR resulted in delayed tumor growth as compared to chemotherapy alone. Conclusions: Use of medium potency statins is associated with improved outcomes after frontline RCHOP in patients with DLBCL. This was further confirmed in functional in-vitro and in-vivo studies. Future interventional studies, aimed at improving outcomes in these patients using this novel combination, are warranted. Disclosures Westin: Amgen: Consultancy; 47: Research Funding; Kite: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Morphosys: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Curis: Consultancy, Research Funding; Astra Zeneca: Consultancy, Research Funding. Nastoupil:Gamida Cell: Honoraria; Merck: Research Funding; TG Therapeutics: Honoraria, Research Funding; Karus Therapeutics: Research Funding; Janssen: Honoraria, Research Funding; LAM Therapeutics: Research Funding; Novartis: Honoraria, Research Funding; Bayer: Honoraria; Celgene: Honoraria, Research Funding; Genentech, Inc.: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Gilead/KITE: Honoraria. Neelapu:Bristol-Myers Squibb: Other: personal fees, Research Funding; Merck: Other: personal fees, Research Funding; Kite, a Gilead Company: Other: personal fees, Research Funding; Pfizer: Other: personal fees; Celgene: Other: personal fees, Research Funding; Novartis: Other: personal fees; Karus Therapeutics: Research Funding; N/A: Other; Takeda Pharmaceuticals: Patents & Royalties; Acerta: Research Funding; Cellectis: Research Funding; Poseida: Research Funding; Precision Biosciences: Other: personal fees, Research Funding; Legend Biotech: Other; Adicet Bio: Other; Allogene Therapeutics: Other: personal fees, Research Funding; Cell Medica/Kuur: Other: personal fees; Calibr: Other; Incyte: Other: personal fees; Unum Therapeutics: Other, Research Funding. Landgraf:NCI/NIH: Research Funding. Vega:NCI: Research Funding.

scholarly journals Preparation and preclinical evaluation of aceclofenac loaded pectinate mucoadhesive microspheres

2012 ◽  
Vol 2 (1) ◽  
pp. 8 ◽  
Author(s):  
Santanu Chakraborty ◽  
Priyanka Nayak ◽  
Bala Murali Krishna ◽  
Madhusmruti Khandai ◽  
Ashoke Kumar Ghosh
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Polymer Concentration ◽  
Research Work ◽  
In Vivo Studies ◽  
Systemic Absorption ◽  
Cross Linking ◽  
Significant Difference

The aim of the present research work was to fabricate aceclofenac loaded pectinate microspheres by ionic gelation method and evaluate the effect of different cross-linking agents and polymer concentration on particle size, encapsulation efficacy and drug release behavior. It was also investigated that whether this pectinate dosage form was able to target the drug release in intestinal region and prevent the different side effect associated with the drug in stomach or not. It was observed that particle size, encapsulation efficacy and in vitro drug release were largely depended on polymer concentration and cross-linking agents. It was also observed that pectinate microspheres showed excellent pH depended mucoadhesive properties and they were able to restrict the drug release in stomach. <em>In vitro</em> drug release study showed that alminium-pectinate microspheres have more sustaining property as compared to barium-pectinate microspheres. Holm-Sidak multiple comparison analysis suggested a significant difference in measured t<sub>50%</sub> values among all the formulations with same cross-linking agent. In vivo studies revealed that the anti inflammatory and analgesic effects induced by pectinate microspheres were significantly high and prolonged as compared to pure drug. So, pectinate microspheres can be an excellent carrier for targeting the delivery of aceclofenac as well as help in improving the patient compliance by prolonging the systemic absorption.

scholarly journals Azaspiracids Increase Mitochondrial Dehydrogenases Activity in Hepatocytes: Involvement of Potassium and Chloride Ions

Marine Drugs ◽  
2019 ◽  
Vol 17 (5) ◽  
pp. 276 ◽  
Author(s):  
Marco Pelin ◽  
Jane Kilcoyne ◽  
Chiara Florio ◽  
Philipp Hess ◽  
Aurelia Tubaro ◽  
...  
Keyword(s):  
Chloride Channels ◽  
Gastrointestinal Symptoms ◽  
In Vitro Study ◽  
Chloride Ions ◽  
In Vivo Studies ◽  
The European Union ◽  
Channel Inhibition ◽  
Dehydrogenases Activity

Background: Azaspiracids (AZAs) are marine toxins that are produced by Azadinium and Amphidoma dinoflagellates that can contaminate edible shellfish inducing a foodborne poisoning in humans, which is characterized by gastrointestinal symptoms. Among these, AZA1, -2, and -3 are regulated in the European Union, being the most important in terms of occurrence and toxicity. In vivo studies in mice showed that, in addition to gastrointestinal effects, AZA1 induces liver alterations that are visible as a swollen organ, with the presence of hepatocellular fat droplets and vacuoles. Hence, an in vitro study was carried out to investigate the effects of AZA1, -2, and -3 on liver cells, using human non-tumor IHH hepatocytes. Results: The exposure of IHH cells to AZA1, -2, or -3 (5 × 10−12–1 × 10−7 M) for 24 h did not affect the cell viability and proliferation (Sulforhodamine B assay and 3H-Thymidine incorporation assay), but they induced a significant concentration-dependent increase of mitochondrial dehydrogenases activity (MTT reduction assay). This effect depends on the activity of mitochondrial electron transport chain complex I and II, being counteracted by rotenone and tenoyl trifluoroacetone, respectively. Furthermore, AZAs-increased mitochondrial dehydrogenase activity was almost totally suppressed in the K+-, Cl−-, and Na+-free media and sensitive to the specific inhibitors of KATP and hERG potassium channels, Na+/K+, ATPase, and cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels. Conclusions: These results suggest that AZA mitochondrial effects in hepatocytes derive from an imbalance of intracellular levels of K+ and, in particular, Cl− ions, as demonstrated by the selective reduction of toxin effects by CFTR chloride channel inhibition.

scholarly journals 1074-152 Will combinations of multiple agents produce more robust contrast imaging? An in vitro study and in vivo studies in dogs

2004 ◽  
Vol 43 (5) ◽  
pp. A328
Author(s):  
Xiaokui Li ◽  
Hui Jiang ◽  
Diane Paine ◽  
Zuhua Mao ◽  
Aarti Hejmadi Bhat ◽  
...  
Keyword(s):  
In Vitro Study ◽  
Vitro Study ◽  
In Vivo Studies ◽  
Multiple Agents ◽  
Contrast Imaging

scholarly journals Metallothionein-I/II Knockout Mice Aggravate Mitochondrial Superoxide Production and Peroxiredoxin 3 Expression in Thyroid after Excessive Iodide Exposure

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Na Zhang ◽  
Lingyan Wang ◽  
Qi Duan ◽  
Laixiang Lin ◽  
Mohamed Ahmed ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Urinary Iodine ◽  
In Vitro Study ◽  
Superoxide Production ◽  
Mitochondrial Oxidative Stress ◽  
Mitochondrial Superoxide ◽  
Iodine Level ◽  
Significant Difference

Purpose. We aim to figure out the effect of metallothioneins on iodide excess induced oxidative stress in the thyroid.Methods. Eight-week-old MT-I/II knockout (MT-I/II KO) mice and background-matched wild-type (WT) mice were used. Mitochondrial superoxide production and peroxiredoxin (Prx) 3 expression were measured.Results. In in vitro study, more significant increases in mitochondrial superoxide production and Prx 3 expression were detected in the MT-I/II KO groups. In in vivo study, significantly higher concentrations of urinary iodine level were detected in MT-I/II KO mice in 100 HI group. Compared to the NI group, there was no significant difference existing in serum thyroid hormones level in either groups (P>0.05), while the mitochondrial superoxide production was significantly increased in 100 HI groups with significantly increased LDH activity and decreased relative cell viability. Compared to WT mice, more significant changes were detected in MT-I/II KO mice in 100 HI groups. No significant differences were detected between the NI group and 10 HI group in both the MT-I/II KO and WT mice groups (P>0.05).Conclusions. Iodide excess in a thyroid without MT I/II protection may result in strong mitochondrial oxidative stress, which further leads to the damage of thyrocytes.

Effect of Single Dose In Vivo Propranolol Therapy on In Vitro Adhesion of Human SS RBC.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1234-1234 ◽  
Author(s):  
Laura M. De Castro ◽  
Jude C. Jonassaint ◽  
Jennifer G. Johnson ◽  
Milena Batchvarova ◽  
Marilyn J. Telen
Keyword(s):  
Safety Data ◽  
Study Drug ◽  
Flow Chamber ◽  
In Vivo Studies ◽  
Dependent Manner ◽  
Number Of Patients ◽  
Significant Difference ◽  
Before And After

Abstract Sickle red blood cells (SS RBC) are abnormally adhesive to both endothelial cells (ECs) and components of the extracellular matrix (ECM). Epinephrine (epi) has been shown to elevate cAMP in SS RBC and increase adhesion of SS RBC to ECs in a protein kinase A-dependent manner. In vitro and in vivo studies performed in our lab have led to the hypothesis that adrenergic stimuli such as epi may initiate or exacerbate vaso-occlusion and thus contribute to the association of vaso-occlusive events with physiologic stress. We are conducting a prospective, dose-escalation pilot clinical study to investigate whether in vivo administration of one dose of propranolol either down-regulates baseline SS RBC adhesion in vitro or prevents its upregulation by epi. In addition, this study will provide additional safety data regarding the use of propranolol in normotensive patients with sickle cell disease (SCD). Figure Figure To date, we have completed the first two dose cohorts. 11 subjects (9 SS and 1 Sβ° thalassemia; 7 females, 3 males) have participated. No severe adverse events were noted. Cohorts 1 and 2 had mean pre-propranolol blood pressure (BP) of 116 (5.9 SD)/ 60.4 (3.98 SD) and 106.8 (4.68 SD)/ 58 (3.9 SD), respectively; this difference was not statistically significant. Minimal and asymptomatic changes in BP were noted in both cohorts after drug administration, with biphasic systolic and diastolic BP nadirs at 45 and 240 minutes. No clinically significant changes in heart rate were observed. Adhesion studies were performed using a graduated height flow chamber on the day of RBC collection. RBC adhesion to ECs was studied before and after epi stimulation and was measured at sheer stresses ranging from 1 to 3 dyne/cm2. Baseline adhesion measurements were validated by comparing percent (%) adhesion assayed at 2 different times within 7 days—at screening and before propranolol dose on the study drug day. We observed no significant difference in adhesion at the 2 different time points without propranolol. Comparison of % adhesion of epi-stimulated RBC to ECs before and 1 hour after propranolol showed that propranolol given in vivo significantly inhibited both non-stimulated and epi-stimulated SS RBC adhesion (p=0.04 and p=0.001, respectively). Lastly, comparison of SS RBC adhesion at both drug doses confirmed the drug-related inhibition of adhesion (p&lt;0.004). We conclude that propranolol administered in vivo decreases SS RBC baseline adhesion to ECs and substantially abrogates epi-stimulated adhesion to ECs, as measured in vitro. Although we have thus far studied only a small number of patients and low propranolol doses, we expect to confirm these results with the 3rd cohort, in which a higher dose of propranolol will be used. If our findings continue to show that propranolol can decrease both SS RBC baseline and epi-stimulated adhesion to ECs, study of propranolol on a larger scale would be warranted in order to ascertain its safety and efficacy as an anti-adhesive therapy in SCD.

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