High-dose Experimental Group Research Articles

Therapeutic effect of adipose-derived mesenchymal stem cells in a porcine model of abdominal sepsis

BackgroundThe term sepsis refers to a complex and heterogeneous syndrome. Although great progress has been made in improving the diagnosis and treatment of this condition, it continues to have a huge impact on morbidity and mortality worldwide. Mesenchymal stem cells are a population of multipotent cells that have immunomodulatory properties, anti-apoptotic effects, and antimicrobial activity. We studied these capacities in a porcine model of peritoneal sepsis.MethodsWe infused human adipose-derived mesenchymal stem cells (ADSCs) into a porcine model of peritoneal sepsis. Twenty piglets were treated with antibiotics alone (control group) or antibiotics plus peritoneal infusion of ADSCs at a concentration of 2 × 106 cells/kg or 4 × 106 cells/kg (low- and high-dose experimental groups, respectively). The animals were evaluated at different time points to determine their clinical status, biochemical and hematologic parameters, presence of inflammatory cytokines and chemokines in blood and peritoneal fluid, and finally by histologic analysis of the organs of the peritoneal cavity.ResultsOne day after sepsis induction, all animals presented peritonitis with bacterial infection as well as elevated C-reactive protein, haptoglobin, IL-1Ra, IL-6, and IL-1b. Xenogeneic ADSC infusion did not elicit an immune response, and peritoneal administration of the treatment was safe and feasible. One day after infusion, the two experimental groups showed a superior physical condition (e.g., mobility, feeding) and a significant increase of IL-10 and TGF-β in blood and a decrease of IL-1Ra, IL-1b, and IL-6. After 7 days, all animals treated with ADSCs had better results concerning blood biomarkers, and histopathological analysis revealed a lower degree of inflammatory cell infiltration of the organs of the peritoneal cavity.ConclusionsIntraperitoneal administration of ADSCs as an adjuvant therapy for sepsis improves the outcome and diminishes the effects of peritonitis and associated organ damage by regulating the immune system and reducing intra-abdominal adhesions in a clinically relevant porcine model of abdominal sepsis.

Decrease in Body Weight and Liver Weight of Pups in Swiss Albino Mice by Spearmint Leaves Extract

Objective: To evaluate the effects of spearmint leaves extract on body weight, liver weight and RTWI of pups in Swiss albino mice. Study Design: Experimental study Place and Duration of Study: Anatomy Department, Shaikh Zayed PGMI, Lahore from 1st March 2014 to 30th June 2014. Methodology: Seven male and 21 female mice were used. After conception female mice were divided into control (A), low dose (B) and high dose (C) experimental groups. There were7 mice in each group. Group A was given distilled water where as group B was given 3g/kg/day and group C were given 6g/kg/day spearmint leaves extract. After 21 days (duration of pregnancy in mice) hysterotomy was done after euthanasia. Three groups of pups were made. These pups were selected randomly and marked as control, low dose and high dose experimental groups (A1, B1 & C1 respectively). Their body weights and liver weights were taken and recorded. Results: Body weight, weight of liver and RTWI of pups in both the experimental groups were decreased significantly with p<0.001 and difference between the experimental groups was also highly significant with p<0.001. Conclusion: The spearmint leaves extract decrease the body weight, weight of liver and RTWI of pups of Swiss Albino mice. Keywords: Spearmint, Garden mint, Herbal tea, Swiss Albino mice, Conception, Body weight, Weight of liver, RTWI

The Promising Effect of Topiramate on Random-Pattern Skin Flap Survival in Rats.

Partial necrosis of skin flaps following plastic and reconstructive surgeries is one of the major problems in these medical interventions. This study was conducted to evaluate the beneficial effects of topiramate an anti-epileptic agent on ischemic random skin flaps. Twenty-four Wistar rats were provided and randomly divided into four experimental groups (control group and low-, intermediate- and high-dose treatment groups). A rat random-pattern skin flap model was performed in all groups, and animals in the low-, intermediate- and high-dose experimental groups were administered topiramate intraperitoneally at doses of 25, 50 and 100 mg/kg, respectively, 1 h before raising the flap and once daily for 7 consecutive days after the initial surgical procedure. Control rats received vehicle according to the same schedule. On postoperative day 7 the flap necrotic area was measured, and tissue samples were stained with hematoxylin and eosin for histological analysis. Furthermore, the oxidative stress in flap tissue was assessed by measuring the activity of superoxide dismutase (SOD), glutathione (GSH) level and the content of malondialdehyde (MDA). Treating animals with 50 and 100 mg/kg topiramate significantly decreased the necrotic flap areas as compared to the control group. Histological studies demonstrated that in intermediate and high dose topiramate groups the inflammatory cell numbers were attenuated and microvessel development were markedly increased. Furthermore, the MDA contents were significantly reduced and GSH levels were significantly increased in these groups as compared to the control group. However, the SOD activity was increased significantly only in high-dose group as compared to the control group. These findings indicated that topiramate in doses of 50 and 100 mg/kg increases random skin flap survival. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Protective effects of icariin on dorsal random skin flap survival: An experimental study

This study was performed to examine the protective effects of icariin (ICA) on ischemic random skin flaps. A rat random-pattern skin flap model was established, and animals in the low-dose and high-dose experimental groups were administered ICA intraperitoneally at doses of 40 and 80 mg/kg, respectively, once daily for 7 days after the initial surgery. Control rats received vehicle according to the same schedule. Survival rates were observed and recorded using transparent graph paper, and flaps were obtained and stained with hematoxylin and eosin (H&E). The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the flap tissue were assessed. The blood flow volume was determined by the laser Doppler method, and tissue expression levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), interleukin-1β, and phosphodiesterase 5 (PDE5) were scored immunohistochemically. The levels of proinflammatory cytokines, including tumor necrosis factor-α and IL-6, were determined by enzyme-linked immunosorbent assay. The main flap survival area was significantly larger in rats treated with ICA than in vehicle-treated controls. H&E staining showed an inhibitory effect of ICA on inflammation, especially at the high dose. In addition, ICA treatment was associated with decreases in the tissue MDA level, proinflammatory cytokine production, and the level of PDE5, but increases in SOD activity, blood flow volume, and the level of VEGF expression. The findings of the present study suggest that ICA is a potential therapeutic agent for random-pattern skin flap necrosis in the clinical setting.

Preliminary mechanism analysis on the hypoglycemic effect of mannan-oligosaccharides

Mannan-oligosaccharides (MOS) and their combined usage with metformin effectively influence the hyperglycemic activity through gut microbiota modulation. Based on previous results, this study aimed to analyze the hyperglycemic mechanism of the composite usage of MOS and metformin in alleviating insulin resistance. The correlation of gut microbiota and molecular mechanism was also established. The results showed that the combination of MOS and metformin could upregulate the IR/IRS-1/PI3K/AKT signaling pathway, thereby featuring the dose dependence of metformin. MOS and their combined usage with metformin could considerably modulate the gut microbiota structure. A total of 6 genera were enriched, and 17 were depleted in the 3 high-dose experimental groups that were assessed at the genus level. Correlation analysis showed that Akkermansia sp. formed a positive relationship with PI3K gene transcription, whereas Anaerostipes sp. and AF12 sp. formed a negative correlation with IR/IRS-1 and Glut4 gene transcription. These findings indicate a significant correlation between gut microbiota and IR-related signal pathway.

Влияние доксорубицина на показатели перекисного окисления липидов и морфоло- гическую картину миокарда у крыс

Anthracycline antibiotic doxorubicin, which has proven cardiovascular toxicity, is often used in the treatment of cancer. The research project was carried out in 21 sexually mature Wistar male rats divided into three groups: control group, high-dose experimental group, in which rats were once injected intraperitoneally with doxorubicin hydrochloride at a dose of 10 mg/kg and low-dose experimental group, in which animals twice received intraperitoneal 2.5 mg/kg doses of doxorubicinhydrochloride at 10-day interval.An increase of malondialdehyde was revealed in the membranes of red blood cells in the high-dose experimental group, while in the low-dose experimental group a reduction in the levels of malondialdehyde and plasma hydroperoxides as well as a decreasing of catalase activity was observed. Intake of doxorubicin also causes venous hyperemia in wide areas of myocardiumalong with increasing of cardiomyocytic cross striation.

Targeting antitumor effect of rhTNF-α fusion protein mediated by matrix metalloproteinase-2.

The aim of this study was to examine the tumor therapy, targeting effects and side effects of tumor-targeting rhTNF-α fusion protein mediated by matrix metalloproteinase-2 in an animal model in order to provide experimental data for future development of drugs. The median lethal dose (LD50) was obtained from acute toxicity experiments. The A549 lung cancer xenograft model was established, and then randomly divided into the saline, standard substance, and low-, middle- and high-dose fusion protein experiment groups. Each group was administered drugs for 18 days. The length and width of the xenografts were measured every three days, after which the xenograft growth curve was drawn. The mice were sacrificed in each group following treatment and the tumor volume and weight were measured. The targeting, effectiveness and toxicity of the transformed fusion protein, and pathological changes of tumor and organ tissues were examined by hematoxylin and eosin (H&E) staining. Additionally, biochemical markers were used to detect damage of various organs after protein processing. Cell apoptosis and angiogenesis were determined using terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL) testing and immunohistochemistry, respectively, in different dose groups. Tumor growth was markedly retarded in the high-dose experimental and standard hTNF-α groups with antitumor rates of 85.91 and 72.25%, respectively, as compared with the control group. Furthermore, the tumor tissue showed obvious apoptosis (the apoptotic index was 78.78 and 66.65%, respectively) and pathological changes in the high-dose experimental and standard hTNF-α groups. Tumor angiogenesis in each fusion protein group was inhibited (P<0.01) and the biochemical markers of various organs were greatly reduced in the high-dose experimental group (P<0.05). This finding indicated that slight toxic effects of fusion proteins were evident for the heart, liver and kidney. The reforming fusion protein can therefore target tumor tissues and efficiently kill tumor cells, with few side effects.

Protective effects of oyster extract against hepatic tissue injury in alcoholic liver diseases

Oyster extract is an effective bioactivity component. It has abundant nutritional value and antiviral, antitumor and immune defense functions. The role of oyster extract in treating liver injury has been paid more attention. We use Wistar rats to make alcoholic liver disease model through injecting alcohol into rats’ stomachs. These rats were randomly divided into five groups: model group, control group, low-dose, middle-dose and high-dose experimental group with a dose of 0.12 g kg−1, 0.40 g kg−1, and 1.20 g kg−1 alcoholic. After nine weeks, serum biomarkers (ALT, AST, TG and TCHO), malondialdehyde (MDA), glutathione (GSH), C3a, C5a, IL-17, TNF-α, anti-MAA-HAS IgG, CD3+, CD4+, CD8+, NK cell activation and zinc content were assessed. The results showed that the serum biomarkers(ALT, AST, TG and TCHO), MDA content, anti-MAA-HSA IgG, serum C3a, C5a IL-17 and TNF-α levels of oyster extract treatment groups were significantly decreased in comparison with model group. On the contrary, GSH showed adverse trend. Serum CD3+, CD4+ and NK cell activation were significantly increased in middle-dose group and high-dose group compared with model group, and there was decrease of CD8+ activity in high-dose group. Plasma Zn level was decreased in model group compared with that in control group. Meanwhile, Mean plasma Zn levels increased dramatically following the dose increase of a given oyster extract.