Targeting Platelets Containing Electro-encapsulated lloprost to Balloon Injured Aorta in Rats

1995 ◽  
Vol 73 (03) ◽  
pp. 535-542 ◽  
Author(s):  
N Crawford ◽  
A Chajara ◽  
G Pfliegler ◽  
B EI Gamal ◽  
L Brewer ◽  
...  
Keyword(s):  
Time Course ◽  
Therapeutic Potential ◽  
Simple Procedure ◽  
Rat Aorta ◽  
Balloon Injury ◽  
Post Injury ◽  
Antiproliferative Effects ◽  
Platelet Deposition ◽  
Total Dna ◽  
Novel Drug

SummaryDrugs can be electro-encapsulated within platelets and targeted to damaged blood vessels by exploiting the platelet’s natural haemostatic properties to adhere to collagen and other vessel wall constituents revealed by injury. A rat aorta balloon angioplasty model has been used to study the effect on platelet deposition of giving iloprost loaded platelets i.v. during the balloon injury. After labelling the circulating platelets with 111-Indium before balloon injury, time course studies showed maximum platelet deposition on the injured aorta occurred at about 1 h post-injury and the deposition remained stable over the next 2-3 h. When iloprost-loaded platelets were given i.v. during injury and the circulating platelet pool labelled with 111-Indium 30 min later, platelet deposition, measured at 2 h postinjury, was substantially and significantly reduced compared with control platelet treatment. Some antiproliferative effects of iloprost-loaded platelets given i.v. during injury have also been observed. Whereas the incorporation of [3H]-thymidine into aorta intima-media DNA at 3 days post injury was 62-fold higher in balloon injured rats than in control sham operated rats, thymidine incorporation into intima/media of rats which had received iloprost loaded platelets during injury was reduced as compared with rats subjected only to the injury procedure. The reduction was only of near significance, however, but at 14 days after injury the total DNA content of the aorta intima/media of rats given iloprost loaded platelets during injury was significantly reduced. Although iloprost loaded platelets can clearly inhibit excessive platelet deposition, other encapsulated agents may have greater anti-proliferative effects. These studies have shown that drug loaded platelets can be targeted to injured arteries, where they may be retained as depots for local release. We believe this novel drug delivery protocol may have therapeutic potential in reducing the incidence of occlusion and restenosis after angioplasty and thrombolysis treatment. Electro-encapsulation of drugs into platelets is a simple procedure and, using autologous and fully biocompatible and biodegradable platelets as delivery vehicles, might overcome some of the immunological and toxicological problems which have been encountered with other delivery vectors such as liposomes, microbeads, synthetic microcapsules and antibodies.

Primordial science and pioneering approaches of guggul for chronic ailments – A modernized review

2020 ◽  
Vol 7 (2) ◽  
pp. 14-20
Author(s):  
Jamal Basha D ◽  
Kumar P R ◽  
Ranganayakulu D
Keyword(s):  
Water Solubility ◽  
Therapeutic Potential ◽  
Chemical Constituents ◽  
Signs And Symptoms ◽  
Dosage Forms ◽  
The Novel ◽  
Lipids Metabolism ◽  
Clinical Conditions ◽  
Novel Drug ◽  
Conventional Dosage

An oleo gum resin guggulu is a product which obtained as a result of gummosis from the bark of Commiphora wightii (Arnott) Bhandari [syn. Commiphoramukul (Hook. Ex Stocks) Family, Burseraceae]. It has been known for its immense applicability in the Ayurveda since time immemorial for the treatment of variety of disorders such as inflammation, gout, rheumatism, impotence, leprosy, obesity, and disorders of lipids metabolism. It is a mixture of phytoconstituents like terpenoids, steroids, flavonoids, guggultetrols, lignans, sugars, and amino acids. This review is an effort to compile all the information available on all of its chemical constituents which are responsible for its therapeutic potential, limitation of guggul extracts and the necessity of novel principles for gum guggul. Nowadays, Guggul is available as the marketed formulation for curing numerous clinical conditions and is accessible in combination with various other ingredients. Though conventional dosage form shows the dominance as patient compliance and easy availability, yet it has found to pose the problems like dose fluctuation, peak-valley effect, non-adjustment of the administered drug, invasiveness etc. Guggul lacks its desired effect due to its low bioavailability and water solubility. This makes it a partial or a deficient therapy for remedy of many signs and symptoms. Novel drug delivery system (NDDS), a new approach and has excluded many of drawbacks exhibited by conventional dosage forms. Some of the novel dosage forms of guggul has been formed like nanoparticles, nanovesicles, gugglusomes and proniosomal gel. But still, the novel formulations for guggul has its less outspread in the market. Guggul can be executed as a profitable drug using NDDS. There is a need to highlight the unidentified and unexplained facts about guggul so as to make it more efficacious and effective in terms of bioavailability and aqueous insolubility.

Herbal Liposomes: Natural Network for Targeted Drug Delivery System

2021 ◽  
pp. 31-41
Author(s):  
Vijay R. Salunkhe ◽  
Prasanna S. Patil ◽  
Ganesh H. Wadkar ◽  
Somnath D. Bhinge
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Targeted Drug Delivery ◽  
Therapeutic Potential ◽  
Herbal Medicines ◽  
Lipid Solubility ◽  
Liposomal Formulations ◽  
Novel Drug ◽  
Herbal Formulations

Herbal medicines have tremendous therapeutic potential that can explored across various effective drug delivery system. Decoctions, herbal teas, tinctures, glyceritum, oxymel, and use much soap, herbal tablets, herbal capsules, and herbal cream, herbal books, and prepared the confection of the most commonly available forms of dosage. The less use of herbal formulations in recent decades due to their lack of standardization. It is possible to use plant extract and isolated constituents to overcome this problem. But these phytoconstituents are suffering from drawbacks, mostly due to problems with stability and low lipid solubility. Novel drug delivery such as liposomes plays an important role in problem solving. Infact, compliance with the patient also improves. The review article discusses the recent status of new herbal liposomal formulations and describes the different ways in which these formulations are prepared.

Stimulation of angiotensin subtype 2 receptor reduces basal cGMP levels in the neointima of rat aorta after balloon injury

1997 ◽  
Vol 28 (1) ◽  
pp. 113-117 ◽  
Author(s):  
Masao Moroi ◽  
Masayuki Fukazawa ◽  
Michiro Ishikawa ◽  
Jo Aikawa ◽  
Atsushi Namiki ◽  
...  
Keyword(s):  
Rat Aorta ◽  
Balloon Injury ◽  
Stimulation Of

scholarly journals Time course of doxorubicin accumulation and dysfunction in the rat aorta

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Noah M. Gibson ◽  
David S. Hydock ◽  
Reid Hayward
Keyword(s):  
Time Course ◽  
Rat Aorta

Abstract TP83: Stress Exacerbates Global Ischemia-induced Inflammatory Response: Intervention by Progesterone

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Claudia Espinosa-Garcia ◽  
Iqbal Sayeed ◽  
Seema Yousuf ◽  
Fahim Atif ◽  
Elena G Sergeeva ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Therapeutic Potential ◽  
Neuronal Loss ◽  
Global Ischemia ◽  
Male Rats ◽  
Post Injury ◽  
Vessel Occlusion ◽  
Nissl Staining ◽  
Increased Risk ◽  
Factor Expression

Introduction: Stress is associated with increased risk of stroke and poor prognosis, but the mechanisms through which stress may alter stroke outcome remain elusive. Stress compromises neuronal survival and neuroinflammation following an ischemic attack. Post-ischemic inflammatory response involves the activation of microglia, which can be polarized from a harmful M1 phenotype which expresses pro-inflammatory cytokines, to a protective M2 phenotype which releases neurotrophic factors. We hypothesize that progesterone (PROG) will improve global ischemia outcome by modulating microglial polarization in stressed ischemic animals. Methods: Adult male rats were exposed to social defeat stress over 8 consecutive days. Then, rats were subjected to 8 min of global ischemia by the four-vessel occlusion model. PROG (8 mg/Kg/b.w.) was administered by intraperitoneal injection at 2 h post-ischemia followed by subcutaneous injections at 6 h and once every 24 h post-injury for 5 days, and then 2 days with progressively halved dosages. Animals were sacrificed at 7 days post-ischemia. Neuronal loss was assessed by Nissl staining, M1/M2 polarization markers were assessed by immunofluorescence, and pro-inflammatory cytokine and growth factor expression were assessed by western blot. Results: Results revealed extensive neuronal loss and exacerbated microglial activation in hippocampal CA1 region of stressed ischemic rats. Remarkably, both M1 and M2 markers increased. PROG treatment attenuated neuronal loss, robustly reduced M1/M2 markers and significantly increased brain-derived neurotrophic factor expression in the stressed ischemic hippocampus. Conclusion: Our data demonstrate that PROG can modulate neuroinflammation after global ischemic injury by changing microglial phenotype in certain vulnerable brain areas like the hippocampus. These findings support the therapeutic potential of PROG for treating global ischemia with comorbid stress.

scholarly journals Early pH Changes in Musculoskeletal Tissues upon Injury—Aerobic Catabolic Pathway Activity Linked to Inter-Individual Differences in Local pH

2020 ◽  
Vol 21 (7) ◽  
pp. 2513 ◽  
Author(s):  
Julia C. Berkmann ◽  
Aaron X. Herrera Martin ◽  
Agnes Ellinghaus ◽  
Claudia Schlundt ◽  
Hanna Schell ◽  
...  
Keyword(s):  
Individual Differences ◽  
Animal Models ◽  
Time Course ◽  
Tricarboxylic Acid Cycle ◽  
Controlled Drug Release ◽  
Post Injury ◽  
Ph Changes ◽  
Ph Values ◽  
Local Ph

Local pH is stated to acidify after bone fracture. However, the time course and degree of acidification remain unknown. Whether the acidification pattern within a fracture hematoma is applicable to adjacent muscle hematoma or is exclusive to this regenerative tissue has not been studied to date. Thus, in this study, we aimed to unravel the extent and pattern of acidification in vivo during the early phase post musculoskeletal injury. Local pH changes after fracture and muscle trauma were measured simultaneously in two pre-clinical animal models (sheep/rats) immediately after and up to 48 h post injury. The rat fracture hematoma was further analyzed histologically and metabolomically. In vivo pH measurements in bone and muscle hematoma revealed a local acidification in both animal models, yielding mean pH values in rats of 6.69 and 6.89, with pronounced intra- and inter-individual differences. The metabolomic analysis of the hematomas indicated a link between reduction in tricarboxylic acid cycle activity and pH, thus, metabolic activity within the injured tissues could be causative for the different pH values. The significant acidification within the early musculoskeletal hematoma could enable the employment of the pH for novel, sought-after treatments that allow for spatially and temporally controlled drug release.

scholarly journals CD81 is a novel immunotherapeutic target for B cell lymphoma

2019 ◽  
Vol 216 (7) ◽  
pp. 1497-1508 ◽  
Author(s):  
Felipe Vences-Catalán ◽  
Chiung-Chi Kuo ◽  
Ranjani Rajapaksa ◽  
Caroline Duault ◽  
Noemi Andor ◽  
...  
Keyword(s):  
B Cell ◽  
Therapeutic Potential ◽  
Cell Lymphoma ◽  
Xenograft Model ◽  
B Cell Lymphoma ◽  
Lymphoid Cells ◽  
Antiproliferative Effects ◽  
Biopsy Specimens ◽  
Human Lymphoma ◽  
Human B Cell

The tetraspanin CD81 was initially discovered by screening mAbs elicited against a human B cell lymphoma for their direct antiproliferative effects. We now show that 5A6, one of the mAbs that target CD81, has therapeutic potential. This antibody inhibits the growth of B cell lymphoma in a xenograft model as effectively as rituximab, which is a standard treatment for B cell lymphoma. Importantly, unlike rituximab, which depletes normal as well as malignant B cells, 5A6 selectively kills human lymphoma cells from fresh biopsy specimens while sparing the normal lymphoid cells in the tumor microenvironment. The 5A6 antibody showed a good safety profile when administered to a mouse transgenic for human CD81. Taken together, these data provide the rationale for the development of the 5A6 mAb and its humanized derivatives as a novel treatment against B cell lymphoma.

scholarly journals Longitudinal Changes in Disability Rating Scale Scores: A Secondary Analysis Among Patients With Severe TBI Enrolled in the Epo Clinical Trial

2019 ◽  
Vol 25 (3) ◽  
pp. 293-301 ◽  
Author(s):  
Julia S. Benoit ◽  
H. Julia Hannay ◽  
Jose-Miguel Yamal ◽  
David J. Francis ◽  
Imoigele Aisiku ◽  
...  
Keyword(s):  
Dynamic Process ◽  
Time Course ◽  
Injury Severity ◽  
Rating Scale ◽  
Outcome Measurement ◽  
Response To Treatment ◽  
Post Injury ◽  
Transfusion Threshold ◽  
Disability Rating Scale ◽  
Disability Rating

AbstractObjectives:Long-term neurological response to treatment after a severe traumatic brain injury (sTBI) is a dynamic process. Failure to capture individual heterogeneity in recovery may impact findings from single endpoint sTBI randomized controlled trials (RCT). The present study re-examined the efficacy of erythropoietin (Epo) and transfusion thresholds through longitudinal modeling of sTBI recovery as measured by the Disability Rating Scale (DRS). This study complements the report of primary outcomes in the Epo sTBI RCT, which failed to detect significant effects of acute treatment at 6 months post-injury.Methods:We implemented mixed effects models to characterize the recovery time-course and to examine treatment efficacy as a function of time post-injury and injury severity.Results:The inter-quartile range (25th–75thpercentile) of DRS scores was 20–28 at week1; 8–24 at week 4; and 3–17 at 6 months. TBI severity group was found to significantly interact with Epo randomization group on mean DRS recovery curves. No significant differences in DRS recovery were found in transfusion threshold groups.Conclusions:This study demonstrated the value of taking a comprehensive view of recovery from sTBI in the Epo RCT as a temporally dynamic process that is shaped by both treatment and injury severity, and highlights the importance of the timing of primary outcome measurement. Effects of Epo treatment varied as a function of injury severity and time. Future studies are warranted to understand the possible moderating influence of injury severity on treatment effects pertaining to sTBI recovery. (JINS, 2019,25, 293–301)

Rapid stimulation of Ins (1,4,5)P3 production in rat aorta by NE: correlation with contractile state

1993 ◽  
Vol 264 (1) ◽  
pp. H126-H132
Author(s):  
V. Pijuan ◽  
I. Sukholutskaya ◽  
W. G. Kerrick ◽  
M. Lam ◽  
C. van Breemen ◽  
...  
Keyword(s):  
Time Course ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Rat Aorta ◽  
Release Mechanism ◽  
Maximal Increase ◽  
Contractile State ◽  
Rapid Stimulation ◽  
Relationship Of ◽  
Stimulation Of

Rapid stimulation of Ins(1,4,5)P3 production in rat aorta by NE: correlation with contractile state. Am. J. Physiol. 264 (Heart Circ. Physiol. 33): H126-H132, 1993.--The isomeric composition of inositol phosphates generated in response to norepinephrine (NE) stimulation and the relationship of inositol phosphate production to release of intracellular Ca2+ as measured by contraction were characterized in rat aorta prelabeled with [3H]inositol. NE stimulated a rapid and transient increase in labeled D-myo-inositol 1,4,5-trisphosphate [Ins-(1,4,5)P3] levels. A maximal increase in labeled Ins(1,4,5)P3 occurred within 15 s of stimulation followed by a decline to control levels at 5 min. D-Myo-inositol 1,3,4-trisphosphate [Ins-(1,3,4)P3] and D-myo-inositol 1-monophosphate [Ins(1)P] levels also increased rapidly in response to NE. In contrast to the transient production of Ins(1,4,5)P3, Ins(1,3,4)P3 and Ins(1)P production was maintained in the presence of NE. Half-maximal stimulation of Ins(1,4,5)P3 production and Ca2+ release occurred at 0.3 microM NE, and maximal effects were obtained with 10 microM NE. The concentration-response curve and time course for production of Ins(1,4,5)P3 correlated with the neurotransmitter-induced Ca2+ release from intracellular stores, indicating that the level of Ins(1,4,5)P3 regulated the Ca(2+)-release mechanism. In the continued presence of NE, the intracellular pools did not completely refill with Ca2+ despite the return of Ins-(1,4,5)P3 levels to basal at 5 min. These results demonstrate that NE stimulates a rapid increase in Ins(1,4,5)P3 that correlates with contraction in Ca(2+)-free buffer. The reuptake of Ca2+ into intracellular stores is regulated by a mechanism that may not involve Ins(1,4,5)P3.

scholarly journals Cellular Senescence in Renal and Urinary Tract Disorders

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2420
Author(s):  
Yohan Santin ◽  
Philippe Lluel ◽  
Pascal Rischmann ◽  
Xavier Gamé ◽  
Jeanne Mialet-Perez ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Cellular Senescence ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Senescent Cell ◽  
Post Injury ◽  
Urinary Tract Disorders ◽  
Age Related ◽  
Adverse Remodeling ◽  
Bladder Disorders

Cellular senescence is a state of cell cycle arrest induced by repetitive cell mitoses or different stresses, which is implicated in various physiological or pathological processes. The beneficial or adverse effects of senescent cells depend on their transitory or persistent state. Transient senescence has major beneficial roles promoting successful post-injury repair and inhibiting malignant transformation. On the other hand, persistent accumulation of senescent cells has been associated with chronic diseases and age-related illnesses like renal/urinary tract disorders. The deleterious effects of persistent senescent cells have been related, in part, to their senescence-associated secretory phenotype (SASP) characterized by the release of a variety of factors responsible for chronic inflammation, extracellular matrix adverse remodeling, and fibrosis. Recently, an increase in senescent cell burden has been reported in renal, prostate, and bladder disorders. In this review, we will summarize the molecular mechanisms of senescence and their implication in renal and urinary tract diseases. We will also discuss the differential impacts of transient versus persistent status of cellular senescence, as well as the therapeutic potential of senescent cell targeting in these diseases.

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