Immunosuppressive Potential of Activated Human Amniotic Cells in an Experimental Murine Model of Skin Allo- and Xenotransplantation

Isolated human amniotic cells (hAC) could be used as a source of immunomodulatory factors in regenerative medicine and transplantation. However, in previous experimental studies, native hAC administered to skin graft recipients did not induce graft immunotolerance. To strengthen the immunomodulatory properties of hAC prior to administration to the recipient, we activated them ex vivo using pro-inflammatory cytokines. In this study, we compared the transplantation efficiency of skin allografts (mouse to mouse) and xnografts (rat to mouse) in recipient mice divided into three main groups receiving: 1. Placebo (control group); 2. Cyclosporine A (CsA) [10 or 50 mg/kg body weight (bw)]; 3. suspension of hAC activated ex vivo by IL-1β and INFγ, administered into a tail vein or subcutaneously. During 15 days of observation, hAC administered intravenously or subcutaneously after allotransplantation appeared to be as safe and efficient as CsA at the dose of 10 mg/kg bw in preventing rejection of skin allo- and xenografts. After xenotransplantation, however, only hAC administered intravenously prevented rejection to an extent comparable to CsA. Both CsA (10 mg/kg bw) and activated hAC reduced inflammatory infiltration in the skin (after intravenous injection) and did not increase the concentration of the inflammation marker SAP in serum or percentage of leukocytes in blood. Finally, we concluded that administration of activated hAC is safe and efficient in the presented animal model of skin allo- and xenotransplantation in a route-dependent manner. Activated hAC injected intravenously exhibit an immunosuppressive effect comparable to CsA administered at the dose of 10 mg/kg bw in both allo- and xenotransplantation.

Download Full-text

Ethanol Extract of Achillea fragrantissima Enhances Angiogenesis through Stimulation of VEGF Production

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530321666201230113018 ◽

2020 ◽

Vol 21 ◽

Author(s):

Hana M. Hammad ◽

Amer Imraish ◽

Maysa Al-Hussaini ◽

Malek Zihlif ◽

Amani A. Harb ◽

...

Keyword(s):

Wound Healing ◽

Rural Communities ◽

Ex Vivo ◽

Ethanol Extract ◽

Aortic Ring ◽

Treated Group ◽

Control Group ◽

Dependent Manner ◽

Achillea Fragrantissima

Objective: Achillea fragrantissima L. (Asteraceae) is a traditionally used medicinal herb in the rural communities of Jordan. Methods: The present study evaluated the efficacy of the ethanol extract of this species on angiogenesis in both, ex vivo using rat aortic ring assay and in vivo using rat excision wound model. Results: In concentrations of 50 and 100 µg/ml, the ethanol extract showed angiogenic stimulatory effect and significantly increased length of capillary protrusions around aorta rings of about 60% in comparison to those of untreated aorta rings. In MCF-7 cells, the ethanol extract of A. fragrantissima stimulates the production of VEGF in a dose-dependent manner. 1% and 5% of ethanol extract of A. fragrantissima containing vaseline based ointment was applied on rat excision wounds for six days and was found to be effective in wound healing and maturation of the scar. Both preparations resulted in better wound healing when compared to the untreated control group and vaseline-treated group. This effect was comparable to that induced by MEBO, the positive control. Conclusion: The results indicate that A. fragrantissima has a pro-angiogenic effect, which may act through the VEGF signaling pathway.

Download Full-text

Experimental studies of atrial fibrillation: a comparison of two pacing models

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00999.2007 ◽

2008 ◽

Vol 294 (3) ◽

pp. H1206-H1215 ◽

Cited By ~ 13

Author(s):

Gabriel Laurent ◽

Gordon Moe ◽

Xudong Hu ◽

Howard Leong-Poi ◽

Kim A. Connelly ◽

...

Keyword(s):

Atrial Fibrillation ◽

Left Atrial ◽

Experimental Studies ◽

Severe Heart Failure ◽

Left Ventricular ◽

Control Group ◽

Type Iii Collagen ◽

Atrial Remodeling ◽

Venous Flow ◽

Group 2

Rapid ventricular pacing (RVP) is a well-established animal model of atrial fibrillation (AF). However, this model is limited by a high mortality rate and severe heart failure. The purpose of our study was to assess a new canine model of inducible AF. We performed acute, short-term, simultaneous atrioventricular pacing (SAVP) and RVP (in random order) in 14 dogs for 30 s. SAVP produced more echocardiographic pulmonary venous flow reversal, a greater increase in mean pulmonary capillary wedge pressure, and a significantly greater decrease in left atrial emptying function (−84.4 ± 38.6% vs. −23.7 ± 27.1%, P < 0.05) than RVP. Thirty dogs were randomized to three, longer-term, study groups: eight dogs in the control group (no pacing), eight dogs in the RVP group (2 wk at 240 beats/min followed by 3 wk at 220 beats/min), and fourteen dogs in the SAVP group (2 wk at 220 beats/min). SAVP induced less left ventricular dysfunction but more left atrial dysfunction than RVP. SAVP dogs had similar atrial effective refractory periods as RVP dogs but more heterogeneity in conduction and more AF inducibility (83% vs. 40%, P < 0.05) and maintenance (median 1,660 vs. 710 s, P < 0.05) than RVP dogs. SAVP induced more collagen turnover and was associated with a significantly greater increase in type III collagen in the atria compared with RVP dogs (6.9 ± 1.5 vs. 4.8 ± 1.6, respectively, P < 0.05 vs. 1.1 ± 0.7 in unpaced control dogs). In conclusion, the SAVP model induced profound mechanical and substrate atrial remodeling and reproducible sustained AF. This new model is clinically relevant and may be useful for testing AF interventions.

Download Full-text

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel against Ixodes ricinus and Ixodes scapularis in cats

Parasite ◽

10.1051/parasite/2021019 ◽

2021 ◽

Vol 28 ◽

pp. 23 ◽

Cited By ~ 3

Author(s):

Joe Prullage ◽

Anthony Pfefferkorn ◽

Martin Knaus ◽

Justin Frost ◽

Elizabeth Mitchell ◽

...

Keyword(s):

Ixodes Ricinus ◽

Ixodes Scapularis ◽

Experimental Studies ◽

Control Group ◽

Placebo Control ◽

The Novel ◽

Topical Formulation ◽

Arithmetic Means ◽

Pre Treatment ◽

Robust Evidence

Esafoxolaner is a purified enantiomer of afoxolaner with insecticidal and acaricidal properties. It is combined with eprinomectin and praziquantel in a novel topical endectoparasiticide formulation for cats. The efficacy of this novel formulation was evaluated in three Ixodes ricinus and two Ixodes scapularis experimental studies, with comparable designs. In each study, cats were randomly allocated, based on a pre-treatment tick infestation and count, to a placebo control group or a group treated with the minimum recommended dose of the novel formulation. Cats were infested two days before treatment and weekly thereafter. Immediate efficacy was evaluated 48 h after treatment; persistent efficacy was evaluated 48 h after new weekly infestations for at least one month after the treatment (in one of the studies, the first two weeks of persistent efficacy against I. ricinus were not tested). Efficacy was calculated at each timepoint by comparison of arithmetic means of live ticks found in the control and the treated groups. In the three studies targeting I. ricinus, immediate and persistent efficacies ranged between 91% and 100% for five weeks. In the two studies targeting I. scapularis, immediate and persistent efficacies ranged between 95% and 100%, and 98% and 100% for one month, respectively. These studies provide robust evidence of efficacy of the novel topical formulation of esafoxolaner, eprinomectin and praziquantel against experimental I. ricinus and I. scapularis infestations for at least one month in cats.

Download Full-text

Dapagliflozin Attenuates Diabetic Cardiomyopathy Through Erythropoietin Up-Regulation of AKT/JAK/MAPK Pathways in Streptozotocin-Induced Diabetic Rats

10.21203/rs.3.rs-472044/v1 ◽

2021 ◽

Author(s):

Nora El-Sayed ◽

Yasser M. Mostafa ◽

Noha M AboGresha ◽

Amal A.M. Ahmed ◽

Islam Z. Mahmoud ◽

...

Keyword(s):

Diabetic Cardiomyopathy ◽

Diabetic Rats ◽

Cardiac Cells ◽

Control Group ◽

Histological Structure ◽

Dependent Manner ◽

Functional Changes ◽

Mapk Cascades ◽

Group 2 ◽

Histopathological Studies

Abstract Purpose: This study was designed to investigate the mechanism of Dapagliflozin (Dapa) cardioprotection against diabetic cardiomyopathy (DCM). Structural and functional changes in the heart as well as decrease of Erythropoietin (EPO) levels were reported in DCM. EPO simultaneously activates three pathways: the Janus-activated kinase–signal transducer and activator of transcription (JAK2/STAT5), phosphatidylinositol-3-kinase-Akt (PI3K/Akt), and extracellular signal-related kinase (ERK/MAPK) cascades, that result in proliferation and differentiation of cardiac cells.Methods and Results: DCM was induced by a high fat diet for 10 weeks followed by administration of streptozotocin. After confirmation of diabetes, rats were divided randomly to 5 groups: Group 1; normal control group, Group 2; untreated diabetic group and Groups (3-5); diabetic groups received Dapa daily (0.75 mg, 1.5 or 3 mg /Kg, p.o) respectively for a month. At the end of the experiment, full anaesthesia was induced in all rats using ether inhalation and ECG was recorded. Blood samples were collected then rats were sacrificed and their heart were dissected out and processed for biochemical and histopathological studies. Untreated diabetic rats showed abnormal ECG pattern, elevation of serum cardiac enzymes, decrease EPO levels, downregulation of P-Akt, P-JAK2 and pMAPK pathways, abnormal histological structure of the heart and increase immunostaining intensity of P53 and TNF α in the cardiomyocytes. Dapa in a dose dependent manner attenuated the alterations in the previously mentioned parameters. Conclusion: The cardioprotective effect of Dapa could be mediated by increasing EPO levels and activation of P-Akt, P-JAK2 and pMAPK signalling cascades which in turn decrease apoptosis.

Download Full-text

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel against Echinococcus multilocularis infections in cats

Parasite ◽

10.1051/parasite/2021025 ◽

2021 ◽

Vol 28 ◽

pp. 29

Author(s):

Joe Prullage ◽

Dwight Bowman ◽

Michael Ulrich ◽

Eric Tielemans

Keyword(s):

Echinococcus Multilocularis ◽

Experimental Studies ◽

The United States ◽

Treated Group ◽

Control Group ◽

Placebo Control ◽

The Novel ◽

Control Groups ◽

Geometric Means ◽

Placebo Control Group

NexGard® Combo, a novel topical endectoparasiticide formulation for cats combining esafoxolaner, eprinomectin and praziquantel, for the treatment of internal and external parasite infestations, including arthropods, nematodes and cestodes, was tested for efficacy against induced infections of Echinococcus multilocularis in cats, in two experimental studies. The two studies were performed in the United States with the same E. multilocularis isolate sourced locally. In each study, 20 cats were inoculated intra-gastrically with ~30,000 E. multilocularis protoscoleces three weeks before treatment, then ten cats were randomly allocated to a placebo control group or to the novel formulation treated group. Inoculated cats were treated topically once at the minimum recommended dose of the novel formulation, or with an identical volume of placebo. One week after treatment, cats were humanely euthanized for parasite recovery and count. The efficacy calculation was based on comparison of number of scoleces found in the control group and the novel formulation group. In the two control groups, E. multilocularis scoleces were found in five (range: 30–1025) and eight (range 2–345) cats, the geometric means inclusive of the ten cats per group were 8.9 and 28.8, respectively. In the two novel formulation-treated groups, none of the cats harbored any E. multilocularis scoleces, demonstrating 100% efficacy.

Download Full-text

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel against adult cat flea Ctenocephalides felis and flea egg production in cats

Parasite ◽

10.1051/parasite/2021017 ◽

2021 ◽

Vol 28 ◽

pp. 21 ◽

Cited By ~ 2

Author(s):

Eric Tielemans ◽

Prescillia Buellet ◽

David Young ◽

Alta Viljoen ◽

Julian Liebenberg ◽

...

Keyword(s):

Egg Production ◽

Experimental Studies ◽

Ctenocephalides Felis ◽

Control Group ◽

Placebo Control ◽

Immature Stages ◽

The Novel ◽

Cat Flea ◽

Larval Hatching ◽

Adult Cat

Esafoxolaner, a purified enantiomer of afoxolaner with insecticidal and acaricidal properties, is combined with eprinomectin and praziquantel in NexGard® Combo, a novel topical endectoparasiticide formulation for cats. The efficacy of this novel formulation against adult and immature stages of Ctenocephalides felis fleas was tested in four experimental studies. Two studies were designed to test adulticide efficacy, one to test inhibition of immature stages, and one to test both adulticide efficacy and inhibition of immature stages. In each study, cats were randomly allocated to a placebo control group or to a novel formulation group treated once at the minimum recommended dose. Cats were experimentally infested weekly for one to two months with unfed C. felis originating from North America or Europe. For adulticide efficacy evaluations, live fleas were counted 24 h after treatment and after subsequent weekly infestations. For immature stages, flea eggs were collected and counted weekly for evaluation of egg production inhibition and incubated for larval hatching evaluation. In the three studies testing adult fleas, curative efficacies, 24 h after treatment, were 92.1%, 98.3% and 99.7%; preventive weekly efficacies, 24 h after weekly infestations, remained higher than 95.5% for at least one month. In the two studies testing immature stages, egg production and larval hatching was significantly reduced for at least one month. These studies provide robust evidence of efficacy of the novel formulation against experimental adult flea infestations and for the prevention of environmental contamination by immature flea stages, for at least one month.

Download Full-text

THE INFLUENCE OF EXTRACTS FROM PRUNUS DOMESTICA ON DISORDERS OF INTESTINAL PERISTALSIS INDUCED BY BARIUM CHLORIDE ACTION IN MICE

Фармацевтичний часопис ◽

10.11603/2312-0967.2019.4.10669 ◽

2019 ◽

pp. 66-72

Author(s):

Bashar Jabbar Ali Al-Sahlanee ◽

O. Yu. Koshova ◽

I. V. Senyuk

Keyword(s):

Experimental Studies ◽

Barium Chloride ◽

Maximum Activity ◽

Control Group ◽

Dependent Manner ◽

Prunus Domestica ◽

Reference Drug ◽

Polysaccharide Complex ◽

Laxative Effect ◽

Intestinal Peristalsis

The aim of the work. To confirm by experimental studies the laxative activity of fiber-containing extract and extract with polysaccharide complex obtained from the Prunus domestica fruits in a model of intestinal peristalsis damage induced by barium chloride in mice, to identify the most effective extract among them and determine its effective dose. Materials and Methods. Dry extracts from the Prunus domestica fruits (fiber-containing extract (PEF) and extract with polysaccharide complex (PEPC)) were used in the experimental studiesThe investigated extracts were obtained by the original method at the Department of Chemistry of Natural Compounds of the National University of Pharmacy. The study of the laxative effect of the PEF and PEPC extracts was conducted in the model of intestinal peristalsis damage induced by barium chloride in mice. The studied effect was determined by the rate of contrast mass passage through the intestines. Results and Discussion. The introduction of PEF and PEPC at doses of 75 mg/kg, 100 mg/kg, 200 mg/kg and the reference drug natrii picosulfas at a dose of 2.3 mg/kg abolished the spasm of smooth muscles of the stomach and intestine. It was evidenced by the lengthening of contrast mass pathway through the intestines of mice to the level of intact control. Moreover, in the case of the use of PEF extract, the intensity of the laxative activity had a dose-dependent manner: with increasing dose, the intensity of the action increased. At a dose of 200 mg/kg, in contrast to the doses of 75 and 100 mg/kg, the contrast mass pathway was statistically significantly higher than in the control group. The laxative effect of 200 mg/kg PEF extract was 29% (by percentage of the contrast mass pathway to the entire length of the intestine), which exceeded the maximum activity of 100 mg/kg PEPC extract (26 %) and was at the level of the reference drug 2.3 mg/kg natrii picosulfas (27 %). Conclusions. Experimental studies have confirmed the laxative properties of the PEF and PEPC extracts from Prunus domestica fruts in the model of intestinal peristalsis damage induced by barium chloride in mice. The PEF extract showed laxative activity at a dose of 200 mg/kg (29 %), which was higher than the maximum activity of the PEPC extract observed at a dose of 100 mg/kg (26 %) and was at the level of the reference drug natrii picosulfas at a dose of 2.3 mg/kg (27 %). Thus, the fiber-containing extract was identified as the most active between the two extracts. The dose of 200 mg/kg was determined as conditionally effective. Proved intensive laxative effect of the PEF extract probably related to the presence in its chemical composition of homopolysaccharides (59 %).

Download Full-text

BISPHENOL A DOSE- AND TIME-DEPENDENTLY INDUCES OXIDATIVE STRESS IN RAT LIVER MITOCHONDRIA EX VIVO

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i9.26750 ◽

2018 ◽

Vol 11 (9) ◽

pp. 98 ◽

Cited By ~ 2

Author(s):

Mousumi Dutta ◽

Goutam Paul

Keyword(s):

Oxidative Stress ◽

Bisphenol A ◽

Rat Liver ◽

Ex Vivo ◽

Liver Mitochondria ◽

Time Dependent ◽

Incubation Mixture ◽

Rat Liver Mitochondria ◽

Control Group ◽

Dependent Manner

Objective: The probable toxic effects of bisphenol A (BPA) on different physiological functions have been reported in animal models. The role of BPA in mitochondrial oxidative stress has not been reported till date. The present study is aimed to elucidate dose- and time-dependent oxidative stress generation by BPA, respectively, in rat liver mitochondria in ex vivo model. Methods: The incubation mixture of BPA-treated groups containing mitochondria, 50 mM potassium phosphate buffer (pH 7.4), and different concentrations of BPA (20–160 μM/ml) (dissolved in 12% DMSO) in a final volume of 1.0 ml was incubated at 37°C in incubator for different time durations (30 min–2 h). Whereas, the incubation mixture of control group contained DMSO (12%), mitochondria and 50 mM potassium phosphatebuffer (pH 7.4).’ will be replaced by ‘Whereas, the incubation mixture of control group contained the same constituents except BPA. Result: We have observed significant decrease in mitochondrial intactness incubated with BPA in dose- and time-dependent manner under bright field and confocal microscopic study compared to control. Further, we have observed a decrease in mitochondrial reduced glutathione (GSH) content and increase in lipid peroxidation and protein carbonylation levels in dose- and time-dependent manner in BPA-exposed mitochondria. We have found a significant increase in the activity of Mn-superoxide dismutase and decrease in the activities of GSH peroxidase, GSH reductase, pyruvate dehydrogenase, and other three enzymes of Kreb’s cycle dose and time dependently in BPA-exposed mitochondria. The results indicate that exposure to BPA leads to decrease in intactness of mitochondria and increase in oxidative stress in mitochondria isolated from rat liver in a dose- and time-dependent manner. Conclusion: It can be concluded that the incubation of mitochondria isolated from rat liver with BPA, caused oxidative stress-mediated damages in mitochondria in both dose- and time-dependent manners.

Download Full-text

Spirulina platensis Alleviated the Hemotoxicity, Oxidative Damage and Histopathological Alterations of Hydroxychloroquine in Catfish (Clarias gariepinus)

Frontiers in Physiology ◽

10.3389/fphys.2021.683669 ◽

2021 ◽

Vol 12 ◽

Author(s):

Alaa El-Din H. Sayed ◽

Mohamed Hamed ◽

Hamdy A. M. Soliman

Keyword(s):

Spirulina Platensis ◽

Clarias Gariepinus ◽

Treated Group ◽

Protective Role ◽

Control Group ◽

Central Vein ◽

Renal Tubules ◽

Dependent Manner ◽

Hematological Indices ◽

Group 2

The current study aims at evaluating the toxicity of hydroxychloroquine (HCQ) as a pharmaceutical residue in catfish (Clarias gariepinus) and the protective role of Spirulina platensis (SP). Four groups were used in this study: (1) a control group, (2) a group exposed to 3.16 mg/l of HCQ, (3) a group exposed to 3.16 mg/l of HCQ + 10 mg/l of SP, and (4) a group exposed to 3.16 mg/l of HCQ + 20 mg/l of SP for 15 days of exposure. The HCQ-treated group showed a significant decline in the hematological indices and glucose, total protein, and antioxidant levels in relation to the control group, whereas the HCQ-treated group showed a significant increase in the levels of creatinine, uric acid, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) as well as the percentage of poikilocytosis and nuclear abnormalities of RBCs in relation to the control group. The histopathological evaluation of the liver indicated dilation of the central vein, vacuolization, degeneration of hepatocytes and pyknotic nuclei, as well as reduction of glomeruli, dilation of Bowman’s space, and degeneration of renal tubules in the kidney of the HCQ-treated group. Spirulina platensis (SP) rendered the hematological and biochemical indexes as well as antioxidant levels and the histological architecture to normal status in a dose-dependent manner. Accordingly, the current study recommends the use of SP to remedy the toxic effects of HCQ.

Download Full-text

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel against Amblyomma americanum in cats

Parasite ◽

10.1051/parasite/2021021 ◽

2021 ◽

Vol 28 ◽

pp. 25 ◽

Cited By ~ 1

Author(s):

Joe Prullage ◽

Christine Baker ◽

Abdelmoneim Mansour ◽

Scott McCall ◽

David Young ◽

...

Keyword(s):

Experimental Studies ◽

The United States ◽

Treated Group ◽

Amblyomma Americanum ◽

Control Group ◽

Placebo Control ◽

The Novel ◽

Tick Count ◽

Placebo Control Group ◽

Preventive Efficacy

Esafoxolaner, a purified enantiomer of afoxolaner with insecticidal and acaricidal properties, is combined with eprinomectin and praziquantel in NexGard® Combo, a novel topical endectoparasiticide product for cats. The efficacy of this novel formulation was assessed in two experimental studies against induced infestations with Amblyomma americanum, a tick species of major importance, highly prevalent in a large southeastern quarter of the United States. In each study, 10 cats were randomly allocated to a placebo control group and 10 cats to a novel formulation treated group. Infested cats were treated topically once at the minimum recommended dose. Both studies were designed to test curative efficacy on existing infestation, 72 h after treatment, and to test preventive efficacy, 72 h after subsequent weekly (Study #1) or fortnightly (Study #2) infestations for one month. For each infestation, all cats were infested with 50 unfed adult A. americanum. At each tick count, in both studies, at least 8 in 10 placebo control cats were infested with 13 (26%) or more live ticks, demonstrating adequate infestation throughout the studies. Curative efficacy of the novel formulation was 99% in both studies; preventive efficacy was 92% and 100% for at least one month.

Download Full-text