scholarly journals ID: 1006 Allogeneic adipose -derived mesenchymal stem cell transplantion enhanced the expression of angiogenic factors on mouse acute hindlimb ischemia model

2017 ◽  
Vol 4 (S) ◽  
pp. 83
Author(s):  
Ngoc Bich Vu ◽  
Ha Thi-Ngan Le ◽  
Thuy Thi-Thanh Dao ◽  
Lan Thi Phi ◽  
Phuc Van Pham ◽  
...  

The cell migration and/or molecular mechanism in healing of damaged vascular or muscle tissue are emerging field with strong research interest worldwide. This study focuses on evaluating the role of allogenic adipose-derived mesenchymal stem cells (ADMSCs) in restoring damaged tissue through the migration of cells and the expression of genes related to myocyte regeneration and angiogenesis on hindlimb ischemic mouse model. ADMSCs were labeled with GFP (ADMSC-GFP). The proximal end of the femoral blood vessel of mice (over 6 months old) was ligated at 2 positions then cut between the two ties. Hindlimb ischemic mice were randomly divided to 2 groups. Group 1 (n=36) was injected PBS (100 μl), group 2 (n=36) was transplanted ADMSC-GFP (106 cell/100 μl PBS) near the cutting position. The migration of ADMSC-GFP in hindlimb was analyzed by UVVis system. The expression of genes related to angiogenesis and muscle tissue repairing was quantified by real time RT-PCR. Muscle tissue structure was histological analyzed by H&E staining. The result showed that ADMSC existed in grafted hindlimb during 7 days. Grafted cells migrated to other damaged areas such as thighs and heels. Ischemic hindlimb were stimulated to increasing expression of several angiogeneic genes including Flt-1, Flk-1 Ang-2 in both group. Especially, the expression of Ang-2 and myogenic-related gene MyoD were significantly increased in ADMSC-treated group compared to non-treated group; and increased at 28th day compared to 3rd day. The other factors such as HGF, CD31, Myf5, TGF-β also expressed much more in ADMSC treated group than the another one. Muscle histological structure in ADMSC group were siminar the normal mouse after 28 day. Thus, grafted-ADMSC was able to migrate to other area in injured hindlimb, existed for about 7 days and have significant positive effects on stimulating the expression of myogenic and angiogenesis- related genes.

Author(s):  
Khaled M. M. Koriem ◽  
Mahmoud S. Arbid

Abstract Background Lead is a toxic metal that is widely distributed in the environment where caftaric acid (CA) is the ester form of caffeic acid where CA is the major dietary polyphenol present in various foods and beverages. The aim of this study was to evaluate the effect of CA in lead acetate (LA)-associated nephrotoxicity through antidiuretic, antioxidant and anti-apoptotic activities. Methods Forty-eight male albino rats divided into six equal groups; group 1 control injected intraperitoneally (ip) with saline (1 mL/kg of bw) over two weeks period, group 2 injected ip with CA (80 mg/kg of bw) over two weeks period, groups 3, 4, 5 and 6 injected ip with 100 μmol/kg of bw LA over two weeks period where groups 4, 5 & 6 co-injected ip with 1-deamino-8-D-arginine vasopressin (dDAVP) drug (1 mg/kg of bw), CA (40 mg/kg of bw), and CA (80 mg/kg of bw), respectively. Results The results obtained revealed that LA induced a significant decrease in kidney weight and serum sodium, potassium and chloride, but caused a significant increase in urinary volume, urinary excretion of sodium, potassium and chloride, serum urea, creatinine and uric acid. The LA also caused a significant decrease in kidney superoxide dismutase, glutathione peroxidase and induced a significant decrease in glutathione level while caused an increase in lipid peroxidation level. In addition, LA caused a decrease in p53 expression while induced an increase in bcl-2 expression in the kidney tissues. Co-injection of CA to LA-treated group restored all the above parameters to approach the normal values. The results supported with histopathological examinations. Conclusions In conclusion, the effect of CA on LA-related nephrotoxicity was occurred through antidiuretic, antioxidant, anti-apoptotic activities where the effect of CA was dose dependent.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Michele Kaplan ◽  
Zana Kalajzic ◽  
Thomas Choi ◽  
Imad Maleeh ◽  
Christopher L. Ricupero ◽  
...  

Abstract Background Orthodontic tooth movement (OTM) has been shown to induce osteocyte apoptosis in alveolar bone shortly after force application. However, how osteocyte apoptosis affects orthodontic tooth movement is unknown. The goal of this study was to assess the effect of inhibition of osteocyte apoptosis on osteoclastogenesis, changes in the alveolar bone density, and the magnitude of OTM using a bisphosphonate analog (IG9402), a drug that affects osteocyte and osteoblast apoptosis but does not affect osteoclasts. Material and methods Two sets of experiments were performed. Experiment 1 was used to specifically evaluate the effect of IG9402 on osteocyte apoptosis in the alveolar bone during 24 h of OTM. For this experiment, twelve mice were divided into two groups: group 1, saline administration + OTM24-h (n=6), and group 2, IG9402 administration + OTM24-h (n=6). The contralateral unloaded sides served as the control. The goal of experiment 2 was to evaluate the role of osteocyte apoptosis on OTM magnitude and osteoclastogenesis 10 days after OTM. Twenty mice were divided into 4 groups: group 1, saline administration without OTM (n=5); group 2, IG9402 administration without OTM (n=5); group 3, saline + OTM10-day (n=6); and group 4, IG9402 + OTM10-day (n=4). For both experiments, tooth movement was achieved using Ultra Light (25g) Sentalloy Closed Coil Springs attached between the first maxillary molar and the central incisor. Linear measurements of tooth movement and alveolar bone density (BVF) were assessed by MicroCT analysis. Cell death (or apoptosis) was assessed by terminal dUTP nick-end labeling (TUNEL) assay, while osteoclast and macrophage formation were assessed by tartrate-resistant acid phosphatase (TRAP) staining and F4/80+ immunostaining. Results We found that IG9402 significantly blocked osteocyte apoptosis in alveolar bone (AB) at 24 h of OTM. At 10 days, IG9402 prevented OTM-induced loss of alveolar bone density and changed the morphology and quality of osteoclasts and macrophages, but did not significantly affect the amount of tooth movement. Conclusion Our study demonstrates that osteocyte apoptosis may play a significant role in osteoclast and macrophage formation during OTM, but does not seem to play a role in the magnitude of orthodontic tooth movement.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
K Banerjee ◽  
B Singla

Abstract Study question To assess the role of subcutaneous granulocyte colony-stimulating factor (G-CSF) in thin endometrium cases. Summary answer G CSF has beneficial role to improve the endometrium thickness in thin endometrium. What is known already Endometrium is very important for embryo implantation and the endometrial thickness is the marker of receptivity of the endometrium. Study design, size, duration Study design - Retrospective analysis Size - 88 infertile females with thin endometrium (< 7 mm) in the age group of 23 to 40 years Duration - one year. Participants/materials, setting, methods In the group 1 of 44 females, subcutaneous infusion of G CSF (300 mcg/ml) was added along with other supplements and if lining was not more than 7 mm in 72 hours, then second infusion was given. In the group 2 of 44 females, only estradiol valerate and sildenafil were given.The efficacy of G CSF was evaluated by assessing the endometrium thickness before embryo transfer, pregnancy rates and clinical pregnancy rates. Main results and the role of chance There was no difference between the two groups regarding demographic variables, egg reserve, sperm parameters, number of embryos transferred and embryo quality. . The pregnancy rate was 60% (24 out of 40 cases) in the group 1 that was significantly higher than in-group 2 that was 31% (9 out of 29 cases) with p value < 0.0001. The clinical pregnancy rate was also significantly higher in-group 1 (55%) as compared to group 2 (24%) with p value < 0.0001. Limitations, reasons for caution Further larger cohort studies are required to explore the subcutaneous role of G CSF in thin endometrium. Wider implications of the findings: Granulocyte colony-stimulating factor has beneficial role to improve the endometrium thickness in thin endometrium. In most of previous studies, the intrauterine infusion of G CSF was given to improve the uterine lining. This is one of the few studies done that showed subcutaneous role of G CSF in thin endometrium. Trial registration number Not applicable


2021 ◽  
Vol 13 (1) ◽  
pp. 57-66
Author(s):  
V. V. Kovalchuk

COVID-19 worsens the course of cerebrovascular diseases (CVD), including chronic cerebral ischaemia (CCI). The Actovegin drug, which has long been widely used in CCI treatment, has an antioxidant and endothelium protective effect. It makes sense to study the effect of Actovegin therapy on the clinical manifestations of CCI in patients with a recent experience of COVID-19.Objective: to evaluate Actovegin efficacy in the treatment of CCI in patients with a recent experience of COVID-19.Patients and methods. The study included 440 patients (234 female; 206 male) with a recent experience of COVID-19, suffering from CCI, their average age being 67.8 years (from 54 to 85 years). All patients were broken down into two groups of 220 people (the patients in Group 1 were administrated Actovegin, the ones in Group 2 – were not). All patients were followed up for 90 days; their condition was assessed by the severity of clinical manifestations of CCI, using special scales and questionnaires.Results and discussion. After 90 days of follow-up, the frequency of complaints of cognitive impairment, sleep disorder, dizziness, fatigue, emotional disorders, and headache in Group 1 was significantly lower than in Group 2 (p<0.05). According to Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), Multidimensional Fatigue Inventory (MFI-20), and Spiegel Sleep Questionnaire (SSQ), the average indicators improved significantly more in Group 1 than in Group 2 (p<0.05). The absence of quality of life impairment and their minimal severity were observed in Group 1 in 77.9%; in Group 2 – in 33.7% (p<0.001). Statistically significant differences between the groups of patients were also observed in relation to emotional state recovery according to the Wakefield Questionnaire and the Spielberger State Trait Anxiety inventory.Conclusion. The observational study demonstrated the efficacy of Actovegin in the treatment of main clinical manifestations of CCI in patients with recent COVID-19 experience.


2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
F Privitera ◽  
V Losi ◽  
I P Monte

Abstract Myocardial dysfunction are the most concerning cardiovascular complications of cancer therapies with a poor prognosis, so it’s critical to detect subclinical cardiac abnormalities in order to start cardioprotective therapy early or increased surveillance frequency. Global longitudinal strain (GLS) by echocardiography is an excellent tool for assessing regional and global left ventricular (LV) function. Mechanical dispersion (MD) reflects heterogeneous myocardial contraction, evaluated in many cardiopathies. We evaluated subclinical myocardial dysfunction by GLS and MD using 2D Speckle-tracking Echo, in order to established if MD could be a predictor of ventricular dysfunction in the field of Cardiotoxicity (CTX). Were enrolled 42 women with breast cancer chemotherapy-treated and underwent to Echo evaluation during 3- and 6-months follow-up, compared to evaluation performed before starting chemotherapy (T0). Depending on chemotherapy type were identified 2 groups: Anthracyclines ± Taxol treated (group 1) and Anti-HER2 treated (group 2). CTX diagnosis was made according ESC criteria: LVEF &lt; 50%, LVEF decrease &gt;10% or GLS decrease &gt;15% compared to previous check. At three months, 28% patients (p &lt; 0,009) developed CTX and, in this group, MD was significantly increased compared to T0 (64,4ms ± 18,6 vs 43,48ms ± 7.88 p &lt; 0,001). This finding was consistent regardless treatment group: 65,2 ms ± 5,30 (p &lt; 0.0001) in group 1 and 63,14 ms ± 36,40 (p 0.02) in group 2. Also, GLS was significantly changed: in CTX patients decreased of 9% compared to T0 (p 0.02), but this finding was consistent in group 1 in which GLS decreased of 18% (p 0,01), while in group 2 decrease only of 5% and wasn’t statistically significant compared to T0 (p = 0,3). These patients were treated by beta-blockers or ACE-inhibitors. At six months there was a normalization of MD value (47.7 ± 15.97 ms in CTX group) that was not statistically significant compared to T0 (p = 0,2) and we have interpreted as consequence of positive effect induced by cardioprotective therapy. We believe that MD is a predictor of ventricular dysfunction earlier than GLS during Anti-HER2 treatment, so in this field MD could integrates information obtained from GLS about subclinical dysfunction.


1987 ◽  
Author(s):  
D J Christie ◽  
H Diaz-Arauzo ◽  
J M Cook

In many cases of drug-induced immunologic thrombocytopenia (DITP), a metabolite, rather than the native drug, is suspected of provoking the destructive drug-dependent antibodies (DDAB) responsible for this severe hemorrhagic disorder. However, this has not previously been investigated for Qn- and Qd-DDAB. We report evidence that the native drugs, and not their metabolites, are the provocative agents in Qn and Qd DITP. Reactions of Qn- and Qd-DDAB with platelets were studied with the native drugs and four of their metabolites: the N-oxide and 10,11-diol derivatives (quinuclidine ring modifications), the des-methyl derivatives (aromatic quinoline ring modification), and 2'-quininone and 2'-quinidinone (2'-oxo derivatives) (also quinoline ring modifications on Qn and Qd, respectively). Five antibodies were studied:two Group 1 DDAB (specific for compounds with native configuration at asymmetric carbon positions), two Group 2 DDAB (similar to Group 1 DDAB but also known to require the methoxy group on the quinuclidine ring for full activity), and one Group 3 DDAB (reactive with the native drug, its stereoisomer, and several nonmetabolic analogs of both compounds) . Using a complement-dependent 51Cr-lysis assay, the reactions of all DDAB with platelets and the four metabolites were similar to 100-fold weaker when compared to reactions obtained with the native drug, with these exceptions:Group 2 DDAB failed to react with the desmethyl and 2'-oxo metabolites and the Group 3 DDAB failed to react with 2'-oxo Qd. This observation shows that the activity of certain DDAB is critically dependent on the native quinoline ring structure. Importantly, none of the DDAB reacted more strongly with any of the metabolites tested when compared with reactions in the presence of the native drug. These findings indicate that DDAB react with platelets preferentially in the presence of the unaltered Qn and Qd molecules and suggest that, while the role of metabolites cannot be entirely ruled out, the native structure of the drug molecule is sufficient to stimulate production of the antibodies responsible for DITP.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y Ge ◽  
A M Smits ◽  
J C Van Munsteren ◽  
T Van Herwaarden ◽  
A M D Vegh ◽  
...  

Abstract Background The autonomic nerve system is essential to maintain homeostasis in the body. In the heart, autonomic innervation is important for adjusting the physiology to the continuously changing demands such as stress responses. After cardiac damage, excessive neurite outgrowth, referred to as autonomic hyperinnervation, can occur which is related to ventricular arrhythmias and sudden cardiac death. The cellular basis for this hyperinnervation is as yet unresolved. Here we hypothesize a role for epicardium derived cells (EPDCs) in stimulating sympathetic neurite outgrowth. Purpose To investigate the potential role of adult EPDCs in promoting sympathetic ganglionic outgrowth towards adult myocardium. Method Fetal murine superior cervical ganglia were dissected and co-cultured with activated adult mesenchymal epicardium-derived cells (EPDCs) or/and adult myocardium in a 3D collagen gel culture system. Four experiment groups were included: Group 1: Vehicle cultures (ganglia cultured without EPDC/myocardium) (n=48); Group 2: ganglia co-cultured with EPDCs (n=38); Group 3: ganglia co-cultured with myocardium (n=95); and group 4: ganglia co-cultured with both EPDCs and myocardium (n=96). The occurrence of neurite outgrowth was assessed in each group. The density of neurites that showed directional sprouting (i.e. sprouting towards myocardium) was assessed as well with a semi-automatic quantification method. Finally, sub-analyses were made by taking gender into account. Results Cervical ganglia cultured with EPDCs alone (group 2) showed increased neurite outgrowth compared to vehicle cultures (group 1), however the neurites did not show directional sprouting towards EPDCs. When co-cultured with myocardium (group 3), directional neurite outgrowth towards myocardium was observed. Compared to the ganglia-myocardium co-cultures, directional outgrowth was significantly increased in co-cultures combining myocardium and EPDCs (group 4), and the neurite density was also significantly augmented. Comparison between males and female ganglia demonstrated that more neurite outgrowth occurred in female-derived ganglia than in male-derived ganglia under the same co-culture conditions. Conclusion Activated adult EPDCs promote sympathetic ganglionic outgrowth in vitro. Sex differences exist in the response of ganglia to EPDCs, and female-derived ganglia appear more sensitive to EPDC-signalling. Results support a role of EPDCs in cardiac autonomic innervation and open avenues for exploring of their role in ventricular hyperinnervation after cardiac damage.


1983 ◽  
Vol 244 (1) ◽  
pp. H115-H120 ◽  
Author(s):  
P. C. Houck ◽  
M. J. Fiksen-Olsen ◽  
S. L. Britton ◽  
J. C. Romero

This study was designed to investigate the possible role of angiotensin and vasopressin in the maintenance of arterial blood pressure during acute blockade of the autonomic nervous system. Two groups of eight dogs each were anesthetized with pentobarbital sodium, and autonomic ganglia were blocked with hexamethonium (20 mg/kg). Thirty minutes later group 1 received the vasopressin antagonist 1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid),2-(O-methyl)tyrosine arginine vasopressin (10 micrograms/kg) followed after a 30-min interval by captopril (1 mg/kg). Group 2 received the same drugs, except the order of administration of vasopressin antagonist and captopril was reversed. Vasopressin antagonist during ganglionic blockade (group 2) produced a greater fall in blood pressure than did captopril during ganglionic blockade (group 1). These data indicate that vasopressin plays a greater pressor role than angiotensin in the acute response to ganglionic blockade. Additional studies were performed to determine if the autonomic nervous system alone can support the resting blood pressure in the anesthetized dog. Combined blockade of angiotensin and vasopressin without autonomic blockade produced a significant decrease in blood pressure, suggesting that the autonomic nervous system alone is not able to support the control blood pressure in the anesthetized dog.


1995 ◽  
Vol 78 (2) ◽  
pp. 491-498 ◽  
Author(s):  
T. D. Murphy ◽  
R. L. Gibson ◽  
T. A. Standaert ◽  
D. E. Woodrum

Group B Streptococcus (GBS) causes an impairment of diaphragmatic pressure generation (Pdi) in 2-wk-old piglets, whereas 4-wk-old piglets are unaffected. In this study, we examined the effect on 4-wk-old piglets of a higher dose of GBS than previously utilized. We sought to determine whether an eicosanoid product of arachidonic acid metabolism accounted for the decrease in Pdi during GBS infusion and whether thromboxane A2 (TxA2) is the putative eicosanoid mediator of decreased Pdi during GBS infusion. Measuring Pdi during phrenic nerve stimulation, we studied four groups of anesthetized spontaneously breathing 4-wk-old piglets. Group 1 (GBS) was infused with live GBS, which caused a decrease in Pdi by 1 h at 20-, 30-, 50-, and 100-Hz stimulation frequencies. Group 2 [GBS + indomethacin (Indo)] was pretreated with Indo before GBS infusion. In the GBS + Indo group, Pdi did not decrease throughout 4 h of GBS infusion. Because Indo proved to be protective of Pdi during GBS infusion, we examined the role of TxA2, the only eicosanoid present at 1 h in the serum of GBS-infused piglets. Group 3 was infused with the TxA2 analogue U-46619 only for 1 h. Group 4 was treated with the TxA2-receptor antagonist SQ-29548 before and concomitant with GBS infusion for 1 h; the SQ-29548 was then discontinued, and GBS was continued for 1 h more. In the U-46619-infused group, Pdi decreased at 1 h, and in the SQ-29548-treated group, Pdi did not decrease during GBS infusion.(ABSTRACT TRUNCATED AT 250 WORDS)


Animals ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1249
Author(s):  
Angelo Quaranta ◽  
Serenella d’Ingeo ◽  
Marcello Siniscalchi

The ability of odors to spontaneously trigger specific memories has been widely demonstrated in humans. Although increasing evidence support the role of olfaction on dogs’ emotions and cognitive processes, very little research has been conducted on its relationship with memory in this species. The present study aimed at investigating the role of olfaction in the recall of detailed memories originally formed in the presence of a specific odor (i.e., vanilla). To test this, three groups of participants were trained with the same spatial learning task while a specific odor (i.e., vanilla) was dispersed in the testing room. Subjects were then divided in three experimental groups and after 24 h delay, they were presented with the same spatial task. The first group (Group 1) performed the task in the presence of a novel odor (i.e., control), whereas the second (Group 2) and the third group (Group 3) carried out the test in the presence of the vanilla odor and no odor (Group 3), respectively. After a brief delay, the test was presented again to the three groups of dogs: subjects of Group 1 were now tested in the presence of the vanilla odor, whereas the Group 2 was tested with the control odor. The Group 3 received no odor in both tests. A significant improvement of dogs’ performance was registered in the control-vanilla odors condition (Group 1), suggesting that the exposure to the odor presented at the encoding time would prompt the recall of spatial memories in dogs.


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