scholarly journals Direct Vascular Effects of Agents Used in the Pharmacotherapy of Cerebrovascular Disease on Isolated Cerebral Vessels

1981 ◽  
Vol 1 (1) ◽  
pp. 117-128 ◽  
Author(s):  
Alan R. Young ◽  
Michele Bouloy ◽  
Jean-François Boussard ◽  
Lars Edvinsson ◽  
Eric T. MacKenzie
Keyword(s):  
Metabolic Disease ◽  
Maximal Response ◽  
Vascular Effects ◽  
Pial Arteries ◽  
Xanthine Derivatives ◽  
Pial Vessels ◽  
Agonist Concentration ◽  
The Mean ◽  
Methyl Xanthine

The direct vasomotor effects of a number of agents used in the therapy of cerebral circulatory and metabolic disease were studied in isolated segments of cat pial vessels in vitro. Studies were repeated eight times generally, thus permitting the calculation of the mean maximum response—termed EAm (in dynes)—and of the molar agonist concentration required to effect the half-maximal response, termed EC50. The results obtained with various agonists were compared to a well-documented vasodilator, acetylcholine ( EAm = −780 dyn; EC50 = 0,029 μm) and a known vasoconstrictor, 5-hydroxytryptamine ( EAm = + 1630 dyn; EC50 = 0.036 μm). Papaverine and its derivatives effected a relaxation of the pial arteries with the following order of potency: YC-93 > papaverine > naftidrofuryl > viquidil. The EC50 for papaverine was 1,5 μm. Methyl xanthine derivatives (aminophylline, pentoxifylline, and theophylline) were essentially inactive, In contrast, drugs that are known to be capable of decreasing the volume of an experimental infarction, many of which are described as α-adrenolytic agents, contracted the isolated cerebrovascular smooth muscle, Their order of efficacy, based on the mean EAm values, was ifenprodil > vincamine > nicergoline > dihydroergotoxine > raubasine, In addition, it was considered worthwhile to determine whether the ifenprodil-induced vasoconstriction occurred when human, rather than cat, pial vessels were studied, Ifenprodil and vincamine contracted the human vessels in a biphasic manner; the EC50 was calculated to be 2,0 and 30 μm. Based on the above observations, the following comments would appear justified, Firstly, an increase in cerebral blood flow does not necessarily mean a compound is a direct vasodilator. Secondly, the vasoconstrictory actions of some agents correlate well with their anti-ischaemic properties (e.g., ifenprodil, vincamine, and nicergoline), Lastly, one action of effective anti-ischaemic agents might be to reduce flow, by vasoconstriction, in hyperaemic tissue: the inverse “steal” effect.

scholarly journals Effects of Bradykinin on Pial Arteries and Arterioles in vitro and in situ

1983 ◽  
Vol 3 (2) ◽  
pp. 231-237 ◽  
Author(s):  
Michael Wahl ◽  
Alan R. Young ◽  
Lars Edvinsson ◽  
Franz Wagner
Keyword(s):  
Maximal Response ◽  
Guinea Pig Ileum ◽  
Response Curves ◽  
Pial Arteries ◽  
Cerebrovascular Resistance ◽  
Resistance Vessels ◽  
Prostaglandin F ◽  
The Stability

The effect of bradykinin on cerebrovascular resistance vessels was investigated by the use of in vitro and in situ preparations. Bradykinin, in the range of 10−10 to 10−5 M, elicited a concentration-dependent vasodilatation on both feline and human pial arteries in vitro; the half-maximal response was found to be approximately at 2.8 × 10−7 M and 1.3 × 10−8 M (EC50), respectively. This dilatatory effect of bradykinin in vitro was found only in arteries preconstricted with prostaglandin F2α or 5-hydroxytryptamine. In order to determine the effects of bradykinin on the diameter of cat pial arteries in situ, perivascular microapplication was employed. The dose-response curves obtained showed vasodilatation; the EC50 and the maximal response (EAm) were 4.4 × 10−7 M and 45.5% at 10−5 M, respectively. Statistically significant (p < 0.01) reactions were observed at 10−7 M and higher concentrations of bradykinin. The observed effects were independent of initial vessel size (80–260 μm). These in situ findings are very similar to those found in vitro. The isolated guinea pig ileum was used to check the stability of the bradykinin solutions. In this instance, a concentration-dependent contraction was found when “freshly prepared” or “5 hours stored” bradykinin was applied, indicating no measurable degradation of bradykinin. We conclude that bradykinin is a powerful vasodilator of both human and feline pial arteries.

scholarly journals Nerve Fibres Containing Gastrin-Releasing Peptide around Pial Vessels

1983 ◽  
Vol 3 (3) ◽  
pp. 386-390 ◽  
Author(s):  
Rolf Uddman ◽  
Lars Edvinsson ◽  
Christer Owman ◽  
Frank Sundler
Keyword(s):  
Spinal Cord ◽  
Guinea Pig ◽  
Cord Blood ◽  
Choroid Plexus ◽  
Blood Vessels ◽  
Nerve Fibres ◽  
Pial Arteries ◽  
Gastrin Releasing Peptide ◽  
Pial Vessels

Nerve fibres containing immunoreactive gastrin-releasing peptide (GRP) were demonstrated around pial blood vessels of cat, guinea pig, rat, and mouse. A sparse supply was found around spinal cord blood vessels, whereas the choroid plexus seemed to be devoid of GRP fibres. Sympathectomy did not affect the number or distribution of the GRP fibres. The administration of neither GRP nor its closely related analogue, bombesin, contracted or dilated feline pial arteries in vitro.

Influence of Platelet Membrane Sialic Acid and Platelet-Associated IgG on Ageing and Sequestration of Blood Platelets in Baboons

1993 ◽  
Vol 70 (04) ◽  
pp. 676-680 ◽  
Author(s):  
H F Kotzé ◽  
V van Wyk ◽  
P N Badenhorst ◽  
A du P Heyns ◽  
J P Roodt ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Life Span ◽  
Blood Platelets ◽  
Senescent Cell ◽  
Platelet Membrane ◽  
Antigen Complex ◽  
The Mean ◽  
Aggregation Of Platelets

SummaryPlatelets were isolated from blood of baboons and treated with neuraminidase to remove platelet membrane sialic acid, a process which artificially ages the platelets. The platelets were then labelled with 111In and their mean life span, in vivo distribution and sites of Sequestration were measured. The effect of removal of sialic acid on the attachment of immunoglobulin to platelets were investigated and related to the Sequestration of the platelets by the spleen, liver, and bone marrow. Removal of sialic acid by neuraminidase did not affect the aggregation of platelets by agonists in vitro, nor their sites of Sequestration. The removal of 0.51 (median, range 0.01 to 2.10) nmol sialic acid/108 platelets shortened their life span by 75 h (median, range 0 to 132) h (n = 19, p <0.001), and there was an exponential correlation between the shortening of the mean platelet life span and the amount of sialic acid removed. The increase in platelet-associated IgG was 0.112 (median, range 0.007 to 0.309) fg/platelet (n = 25, p <0.001) after 0.79 (median, range 0.00 to 6.70) nmol sialic acid/108 platelets was removed (p <0.001). There was an exponential correlation between the shortening of mean platelet life span after the removal of sialic acid and the increase in platelet-associated IgG. The results suggest that platelet membrane sialic acid influences ageing of circulating platelets, and that the loss of sialic acid may have exposed a senescent cell antigen that binds IgG on the platelet membrane. The antibody-antigen complex may then provide a signal to the macrophages that the platelet is old, and can be phagocytosed and destroyed.

The Safety and Antimicrobial Properties of Stabilized Hypochlorous Acid in Acetic Acid Buffer for the Treatment of Acute Wounds—a Human Pilot Study and In Vitro Data

2021 ◽  
pp. 153473462110156
Author(s):  
Ewa A. Burian ◽  
Lubna Sabah ◽  
Klaus Kirketerp-Møller ◽  
Elin Ibstedt ◽  
Magnus M. Fazli ◽  
...  
Keyword(s):  
Pilot Study ◽  
Hypochlorous Acid ◽  
Treatment Time ◽  
Donor Site ◽  
Antimicrobial Properties ◽  
Prolonged Treatment ◽  
Wound Irrigation ◽  
The Mean ◽  
And Performance

Acute wounds may require cleansing to reduce the risk of infection. Stabilized hypochlorous acid in acetic buffer (HOCl + buffer) is a novel wound irrigation solution with antimicrobial properties. We performed a first-in-man, prospective, open-label pilot study to document preliminary safety and performance in the treatment of acute wounds. The study enrolled 12 subjects scheduled for a split-skin graft transplantation, where the donor site was used as a model of an acute wound. The treatment time was 75 s, given on 6 occasions. A total of 7 adverse events were regarded as related to the treatment; all registered as pain during the procedure for 2 subjects. One subject had a wound infection at the donor site. The mean colony-forming unit (CFU) decreased by 41% after the treatment, and the mean epithelialization was 96% on both days 14 (standard deviation [SD] 8%) and 21 (SD 10%). The study provides preliminary support for the safety, well-tolerance, and efficacy of HOCl + buffer for acute wounds. The pain was frequent although resolved quickly. Excellent wound healing and satisfying antimicrobial properties were observed. A subsequent in vitro biofilm study also indicated good antimicrobial activity against Pseudomonas aeruginosa with a 96% mean reduction of CFU, when used for a treatment duration of 15 min ( P < .0001), and a 50% decrease for Staphylococcus aureus ( P = .1010). Future larger studies are needed to evaluate the safety and performance of HOCl + buffer in acute wounds, including the promising antimicrobial effect by prolonged treatment on bacterial biofilms.

scholarly journals Formulation and in vitro evaluation of self-nanoemulsifying liquisolid tablets of furosemide

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lena Dalal ◽  
Abdul Wahab Allaf ◽  
Hind El-Zein
Keyword(s):  
Theoretical Model ◽  
Castor Oil ◽  
In Vivo Studies ◽  
Coating Materials ◽  
Peg 400 ◽  
The Mean ◽  
Usp Apparatus ◽  
Solid System

AbstractSelf-nanoemulsifying drug delivery systems (SNEDDS) were used to enhance the dissolution rate of furosemide as a model for class IV drugs and the system was solidified into liquisolid tablets. SNEDDS of furosemide contained 10% Castor oil, 60% Cremophor EL, and 30% PEG 400. The mean droplets size was 17.9 ± 4.5 nm. The theoretical model was used to calculate the amounts of the carrier (Avicel PH101) and coating materials (Aerosil 200) to prepare liquisolid powder. Carrier/coating materials ratio of 5/1 was used and Ludipress was added to the solid system, thus tablets with hardness of 45 ± 2 N were obtained. Liquisolid tablets showed 2-folds increase in drug release as compared to the generic tablets after 60 min in HCl 0.1 N using USP apparatus-II. Furosemide loaded SNEDDS tablets have great prospects for further in vivo studies, and the theoretical model is useful for calculating the adequate amounts of adsorbents required to solidify these systems.

scholarly journals Survey of Phenolic Acids, Flavonoids and In Vitro Antioxidant Potency Between Fig Peels and Pulps: Chemical and Chemometric Approach

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2574
Author(s):  
Lahcen Hssaini ◽  
Francisca Hernandez ◽  
Manuel Viuda-Martos ◽  
Jamal Charafi ◽  
Rachid Razouk ◽  
...  
Keyword(s):  
Phenolic Acids ◽  
Radical Scavenging ◽  
Fruit Peel ◽  
Mean Values ◽  
Local Cultivar ◽  
Ic50 Values ◽  
The Mean ◽  
Lipid Peroxidation Inhibition ◽  
Almost All

In the present study, chromatic coordinates, phenolic acids, flavonoids and antioxidant capacity assessed by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonate (ABTS) and lipid peroxidation inhibition capacity (LPIC) essays and their relative IC50 were investigated in 25 fig cultivars growing in Morocco. The aims of this study were to determine (i) the variation in these compounds among light and dark-colored cultivars, (ii) their partitioning between fruit peel and pulp and (iii) to display network connections among these variables. Twelve phenolic compounds (PCs) were isolated in peel extract versus eight in pulp samples. Anthocyanins, mainly cyanidin-3,5-diglucoside and cyanidin-3-O-rutinoside, were the predominant compounds in peels, where the mean concentrations were 75.90 ± 18.76 and 77.97 ± 18.95 µg/g dw, respectively. On the other hand, (−)-epicatechin and cyanidin-3-O-rutinoside were the major compounds in the pulp extracts, where the mean values were 5.23 ± 4.03 and 9.01 ± 5.67 µg/g dw, respectively. A two-dimensional hierarchically clustered heatmap was applied to the dataset to explore correlations in the dataset and similarities between cultivars, without dimensionality reduction. Results showed that anthocyanins, particularly pelargonidin-3-O-rutinoside, cyanidin-3,5-diglucoside and cyanidin-3-O-rutinoside, were the main contributors to the peels’ free radical scavenging capacity. This capacity was particularly higher in the peel of dark-colored figs compared to the fruit pulp. The local cultivar “INRA 1301” showed the most promising phenolic profile due to its very high levels of almost all detected PCs, especially (−)-epicatechin, quercetin-3-O-rutinoside, quercetin-3-O-glucoside, cyanidine-3,5-diglucoside, cyanidine-3-O-rutinoside and pelargonidin-3-O-rutinoside (54.66, 141.08, 35.48, 494.08, 478.66, 12.56 µg/g dw, respectively). Having the darkest figs in the collection (L* = 25.72, c* = 22.09 and h° = 20.99), this cultivar has also combined promising IC50 values, which were of 19.85, 40.58 and 124.78 µg/mL for DPPH, ABTS and LPIC essays, respectively.

scholarly journals Comparative Analysis of Different Local Anesthetic Solutions Available in Market: An In Vitro and Clinical Study

2021 ◽  
Author(s):  
Eisha Imran ◽  
Faisal Moeen ◽  
Beenish Abbas ◽  
Bakhtawar Yaqoob ◽  
Mehreen Wajahat ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Local Anesthetic ◽  
Compositional Analysis ◽  
Bacterial Activity ◽  
Similar Composition ◽  
Ph Values ◽  
Significant Difference ◽  
The Mean ◽  
The Difference

Abstract Objectives The study aimed to evaluate and compare various commercially available local anesthetic solutions. Materials and Methods A total of 150 commercially available local anesthetic cartridges of similar composition (2% lidocaine with epinephrine 1:100,000) were randomly collected and divided into 3 groups. The designations of groups were selected from their product names such that each group consisted of 60 cartridges. Group S (Septodont, France) Group M (Medicaine, Korea) and Group H (HD-Caine, Pakistan). The samples were divided into five sub-groups, each consisting of 10 cartridges from each group to investigate each parameter. Results The acquired data was statistically analyzed and compared (using SPSS version 12). Compositional analysis revealed a non-significant (P>0.05) difference when the three Groups were compared with standard lidocaine and epinephrine solutions. The mean pH values of samples from group S, M and H respectively fell within the range of pH values of commercially available solutions. Non-significant difference in EPT values of Group S and H was found when efficacy was compared (p = 0.3), however a significant difference (p < 0.01) was observed in contrast to Group M. Anti-bacterial activity was observed in all the group and a non-significant difference in cell viability values of Group S and M was found (p = 0.6), while the difference was significant in comparison to Group H. Conclusion Within the limitations of these investigations, it appears that the properties of different manufacturers fall within the recommended ranges as mentioned in literature and do not appear to be statistically different in the variables we have tested.

Elimination of three doses of gentamicin over three consecutive days using a polyacrylonitrile-derived filter: An in vitro assessment

2021 ◽  
pp. 039139882110322
Author(s):  
Frédéric J Baud ◽  
Vanessa Seif ◽  
Pascal Houzé ◽  
Jean-Herlé Raphalen ◽  
Benoît Pilmis ◽  
...  
Keyword(s):  
Life Span ◽  
Bolus Dose ◽  
Central Compartment ◽  
Daily Session ◽  
Progressive Decrease ◽  
Time Dependency ◽  
Study Results ◽  
In Vitro Assessment ◽  
The Mean

Introduction: Adsorption of gentamicin in a polyacrylonitrile filter was previously evidenced in a session lasting 6 h using the NeckEpur model. We extended the study over three consecutive days to mimic the 72-h life span of a filter. Methods: Prismaflex® monitor and ST150® filter were used in the continuous diafiltration (CDF) mode at a 2.5 L/h flowrate. The daily session started with a 6-h session of CDF. Thereafter, the 5-L central compartment was changed using a bag free of gentamicin to assess gentamicin release over the following 18 h. Experiments were repeated on Day 2 and stopped at the end of the 6-h session of CDF on Day 3. The experiment was performed in duplicate. Results: At a 2.5 L/h diafiltration flowrate, the mean daily clearances of gentamicin were 5.5, 4.0, and 3.3 L/h, respectively. The mean diafiltration and adsorption ratios in the daily elimination of gentamicin were 32/68%, 58/42%, and 88/12%, respectively. During days 1 and 2, the mean amount of gentamicin released from the ST150® filter were 14 and 34 mg, respectively. Conclusion: The pharmacokinetics of gentamicin over 3 days is strongly altered by adsorption in the same filter with a progressive decrease of elimination by adsorption, suggesting saturation of the filter. One limitation of our study results from the mode of administration using a bolus dose instead of an infusion over 30 min. Adsorption adds a clearance to those of diafiltration. The time-dependency of gentamicin clearance precludes using a constant dosage regimen over the filter’s life span.

scholarly journals Filociclovir Is an Active Antiviral Agent against Ocular Adenovirus Isolates In Vitro and in the Ad5/NZW Rabbit Ocular Model

2021 ◽  
Vol 14 (4) ◽  
pp. 294
Author(s):  
Eric G. Romanowski ◽  
Islam T. M. Hussein ◽  
Steven C. Cardinale ◽  
Michelle M. Butler ◽  
Lucas R. Morin ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Topical Treatment ◽  
Antiviral Agent ◽  
Human Adenovirus ◽  
Treatment Groups ◽  
Ocular Infections ◽  
The Mean ◽  
Eye Infection

Presently, there is no FDA- or EMA-approved antiviral for the treatment of human adenovirus (HAdV) ocular infections. This study determined the antiviral activity of filociclovir (FCV) against ocular HAdV isolates in vitro and in the Ad5/NZW rabbit ocular model. The 50% effective concentrations (EC50) of FCV and cidofovir (CDV) were determined for several ocular HAdV types using standard plaque reduction assays. Rabbits were topically inoculated in both eyes with HAdV5. On day 1, the rabbits were divided into four topical treatment groups: (1) 0.5% FCV 4x/day × 10 d; (2) 0.1% FCV 4x/day × 10 d; (3) 0.5% CDV 2x/day × 7 d; (4) vehicle 4x/day × 10 d. Eyes were cultured for virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14. The resulting viral eye titers were determined using standard plaque assays. The mean in vitro EC50 for FCV against tested HAdV types ranged from 0.50 to 4.68 µM, whereas those treated with CDV ranged from 0.49 to 30.3 µM. In vivo, compared to vehicle, 0.5% FCV, 0.1% FCV, and 0.5% CDV produced lower eye titers, fewer numbers of positive eye cultures, and shorter durations of eye infection. FCV demonstrated anti-adenovirus activity in vitro and in vivo.

Vasorelaxing Activity of Stilbenoid and Phenanthrene Derivatives from Brasiliorchis porphyrostele: Involvement of Smooth Muscle CaV1.2 Channels

Planta Medica ◽  
2020 ◽  
Vol 86 (09) ◽  
pp. 631-642
Author(s):  
Watcharee Waratchareeyakul ◽  
Fabio Fusi ◽  
Miriam Durante ◽  
Amer Ahmed ◽  
Walter Knirsch ◽  
...  
Keyword(s):  
Channel Blocker ◽  
Antihypertensive Agents ◽  
Dependent Manner ◽  
Vascular Effects ◽  
Concentration Dependent Manner ◽  
Spasmolytic Activity ◽  
Depth Analysis ◽  
Cav1.2 Channels ◽  
Vasorelaxant Activity

AbstractFive compounds, 3,4′-dihydroxy-3′,5,5′-trimethoxydihydrostilbene, 1; 3,4′-ihydroxy-3′,5′-dimethoxydihydrostilbene, 2; 3,4′-dihydroxy-5,5′-dimethoxydihydrostilbene, 3; 9,10-dihydro-2,7-dihydroxy-4,6-dimethoxyphenanthrene, 4; and the previously unreported 1,2,6,7-tetrahydroxy-4-methoxyphenanthrene, 5 were isolated from the South American orchid, Brasiliorchis porphyrostele. An in-depth analysis of their vascular effects was performed on in vitro rat aorta rings and tail main artery myocytes. Compounds 1 – 4 were shown to possess vasorelaxant activity on rings pre-contracted by the α 1 receptor agonist phenylephrine, the CaV1.2 stimulator (S)-(−)-Bay K 8644, or depolarized with high K+ concentrations. However, compound 5 was active solely on rings stimulated by 25 mM but not 60 mM K+. The spasmolytic activity of compounds 1 and 4 was significantly affected by the presence of an intact endothelium. The KATP channel blocker glibenclamide and the KV channel blocker 4-aminopyridine significantly antagonized the vasorelaxant activity of compounds 4 and 1, respectively. In patch-clamp experiments, compounds 1 – 4 inhibited Ba2+ current through CaV1.2 channels in a concentration-dependent manner, whereas neither compound 4 nor compound 1 affected K+ currents through KATP and KV channels, respectively. The present in vitro, comprehensive study demonstrates that Brasiliorchis porphyrostele may represent a source of vasoactive agents potentially useful for the development of novel antihypertensive agents that has now to be validated in vivo in animal models of hypertension.

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