Chemoprevention with Enalapril and Aspirin in Men1(+/T) Knockout Mouse Model

2018 ◽  
Vol 107 (3) ◽  
pp. 257-266 ◽  
Author(s):  
Jerena Manoharan ◽  
Volker Fendrich ◽  
Pietro Di Fazio ◽  
Carmen Bollmann ◽  
Silvia Roth ◽  
...  
Keyword(s):  
Mouse Model ◽  
Somatostatin Analogues ◽  
Control Group ◽  
Histopathological Analysis ◽  
Ki 67 ◽  
Chemopreventive Agents ◽  
Knockout Mouse Model ◽  
Angiotensin I Converting Enzyme ◽  
Significant Difference

Pancreatic neuroendocrine neoplasias (pNEN) are the most common cause of death in adult patients with multiple endocrine neoplasia type 1 (MEN1). So far, only few chemopreventive strategies (e.g., with somatostatin analogues) have been evaluated for MEN1 associated pNENs. In this experimental study on 75 Men1(+/T) knockout mice, the effect of aspirin (n = 25) and an inhibitor of angiotensin-I converting enzyme (enalapril, n = 25) compared to controls (n = 25) were evaluated as single chemopreventive strategies for pNENs after 6, 9, 12, 15, and 18 months. After each study period, mice were sacrificed and the resected pancreata were evaluated by histopathological analysis, immunostaining, and real-time PCR. PNEN size and number was measured. Aspirin and enalapril lead to a pNEN size reduction of 80% (167,518 vs. 838,876 µm2, p < 0.001) and 79% (174,758 vs. 838,876 µm2, p < 0.001) compared to controls. Furthermore, aspirin and enalapril treatment resulted in a significant reduction of the number of pNENs by 33%, (p = 0.04) and 41% (p = 0.002) respectively. The apoptosis marker caspase 3 revealed a higher positive expression in pNEN of treated Men1(+/T) mice. Immunostaining of VEGF in pNEN detected a downregulation of its expression in treated Men1(+/T) mice compared to the control group. REL A transcript was significantly downregulated in 18-months treated enalapril Men1(+/T) mice, but not in aspirin-treated Men1(+/T) mice. There was no significant difference in the Ki-67 index. Using a transgenic mouse model that imitates human MEN1, this study provides first evidence that aspirin and enalapril are effective chemopreventive agents that aid in the progression of pNENs.

scholarly journals Investigation of TAGAP gene polymorphism (rs1738074) in Turkish pediatric celiac patients

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Melek Pehlivan ◽  
Tülay K. Ayna ◽  
Maşallah Baran ◽  
Mustafa Soyöz ◽  
Aslı Ö. Koçyiğit ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Disease Risk ◽  
Polymerase Chain Reaction Method ◽  
Control Group ◽  
Healthy Children ◽  
Single Nucleotide ◽  
Significant Difference ◽  
Allele Specific ◽  
And Control

Abstract Objectives There are several hypotheses on the effects of the rs1738074 T/C single nucleotide polymorphism in the TAGAP gene; however, there has been no study on Turkish pediatric patients. We aimed to investigate the association of celiac disease (CD) and type 1 diabetes mellitus (T1DM) comorbidity with the polymorphism in the TAGAP gene of Turkish pediatric patients. Methods Totally, 127 pediatric CD patients and 100 healthy children were included. We determined the polymorphism by the allele-specific polymerase chain reaction method. We used IBM SPSS Statistics version 25.0 and Arlequin 3.5.2 for the statistical analyses. The authors have no conflict of interest. Results It was determined that 72% (n=154) of only CD patients had C allele, whereas 28% (n=60) had T allele. Of the patients with celiac and T1DM, 42.5% (n=17) and 57.5% (n=23) had T and C alleles, respectively. Of the individuals in control group, 67% (n=134) had C allele, whereas 33% (n=66) had T allele. Conclusions There was no significant difference in the genotype and allele frequencies between the patient and control groups (p>0.05). There was no significant association between the disease risk and the polymorphism in our study group.

Effects of GYDENPHY caspules on streptozotocin-induced type 1 diabetic in Swiss mouse model

2021 ◽  
Vol 25 (2) ◽  
pp. 24-32
Author(s):  
Trinh Thach Thi Nguyen ◽  
Duy Tuan Nguyen ◽  
Thanh Ha Tuan Nguyen ◽  
Thi Huong Lan Do ◽  
Hoang Ngan Nguyen
Keyword(s):  
Blood Glucose ◽  
Mouse Model ◽  
Glucose Concentration ◽  
Blood Glucose Concentration ◽  
Insulin Injection ◽  
Swiss Mouse ◽  
Hypoglycemic Effect ◽  
Control Group ◽  
Water Control

Objective: Evaluation the hypoglycemic effect of Gydenphy capsules on Streptozotocin-induced type 1 diabetic in Swiss mouse model. Methods: The type 1 diabetic model was established by intraperitoneal injections of Streptozocin 150mg/kg in Swiss mouse. Then, the Gydenphy were orally administered daily at a dose of 576 mg/kg/day or 1152 mg/kg/day in 10 days. Blood glucose concentration in the Gydenphy oral groups with that of water control group and the intraperitoneal insulin injection group was compared. Results: Blood glucose concentration in the groups using Gydenphy (dose576 mg/kg/24h and dose 1152 mg/kg/24h) significal decreased compared to the distilled water group at (p <0.05 at the time of 4 hours, 8 hours; p <0.01 at the time of 3, 10 days). The hypoglycemic effect of Gydenphy at 576mg/kg/day and 1152 mg/kg/day at 4 hours, 8 hours and 3 days were inferior to insulin 0.1 UI/kg/day for glycemic control. However, the hypoglycemic effect ofGydenphy were equivalent to insulin after 10 consecutive days on treatment. Conclusion: Gydenphy capsules have hypoglycemic effects onStreptozotocin-induced type 1 diabetes in Swiss mouse model.

scholarly journals Clinical significance of intramammary arterial calcifications in diabetic women

2004 ◽  
Vol 61 (2) ◽  
pp. 163-167 ◽  
Author(s):  
Zorica Milosevic ◽  
Jelica Bjekic ◽  
Stanko Radulovic ◽  
Branislav Goldner
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Control Group ◽  
Duration Of Diabetes ◽  
Diabetic Macroangiopathy ◽  
Indirect Sign ◽  
Significant Difference

Background. It is well known that intramammary arterial calcifications diagnosed by mammography as a part of generalized diabetic macroangiopathy may be an indirect sign of diabetes mellitus. Hence, the aim of this study was to determine the incidence of intramammary arterial calcifications, the patient?s age when the calcifications occur, as well as to observe the influence of diabetic polineuropathy, type, and the duration of diabetes on the onset of calcifications, in comparison with nondiabetic women. Methods. Mammographic findings of 113 diabetic female patients (21 with type 1 diabetes and 92 with type 2), as well as of 208 nondiabetic women (the control group) were analyzed in the prospective study. The data about the type of diabetes, its duration, and polineuropathy were obtained using the questionnaire. Statistical differences were determined by Mann-Whitney test. Results. Intramammary arterial calcifications were identified in 33.3% of the women with type 1 diabetes, in 40.2% with type 2, and in 8.2% of the women from the control group, respectively. The differences comparing the women with type 1, as well as type 2 diabetes and the controls were statistically significant (p=0.0001). Women with intramammary arterial calcifications and type 1 diabetes were younger comparing to the control group (median age 52 years, comparing to 67 years of age, p=0.001), while there was no statistically significant difference in age between the women with calcifications and type 2 diabetes (61 years of age) in relation to the control group (p=0.176). The incidence of polineuropathy in diabetic women was higher in the group with intramammary arterial calcifications (52.3%) in comparison to the group without calcifications (26.1%), (p=0.005). The association between intramammary arterial calcifications and the duration of diabetes was not found. Conclusion. The obtained results supported the theory that intramammary arterial calcifications, detected by mammography could serve as markers of co-existing diabetes mellitus and therefore should be specified in radiologic report in case of their early development.

scholarly journals Propolis extract as pulp capping material enhances odontoblast-like cell thickness and type 1 collagen expression (in vivo)

2020 ◽  
Vol 53 (1) ◽  
pp. 1
Author(s):  
Ira Widjiastuti ◽  
Ari Subiyanto ◽  
Evri Kusumah Ningtyas ◽  
Rendy Popyandra ◽  
Michael Golden Kurniawan ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Glass Ionomer Cement ◽  
Control Group ◽  
Propolis Extract ◽  
Pulp Capping ◽  
Collagen Expression ◽  
Group I ◽  
Significant Difference ◽  
Cell Thickness

Background: Propolis is a natural biocompatible material that has been widely studied in dentistry because of its inflammatory, anti-microbial and immunomodulatory properties. One of the active components is caffeic acid phenethyl ester (CAPE). CAPE is effective in stimulating collagen as well as inhibiting the inflammation and degeneration of dental pulp. Purpose: To investigate the post-administration of propolis extract as pulp capping material enhances odontoblast-like cell thickness and type 1 collagen expression in Wistar rats (Rattus Norvegicus) Methods: This research was a true experimental design with a posttest-only control group design. Sixty-three Wistar rats were randomly divided into three groups, with each group consisting of 21 rats: Group I: Positive control; no capping material was administered; Group II: CAPE was administered; Group III: 11% of the propolis extract was administered. All samples were filled with glass ionomer cement. Seven rats from each group were sacrificed after days 7, 14 and 28 of post-pulp capping administration, and their afflicted teeth were subsequently extracted for histologic analysis. Results: No significant difference was seen in odontoblast-like cell thickness after the application of CAPE and propolis on days 7 and 14 (p > 0.05). However, a significant difference was noticed on day 28 (p < 0.05), with the thickness of odontoblast-like cell in CAPE being thinner than that in propolis. A significant difference in the expression of type 1 collagen was observed on days 7, 14 and 28 after the application of the propolis extract compared with CAPE (p < 0.05). Conclusion: The post-administration of propolis extract as a pulp capping material could enhance odontoblast-like cell thickness and type 1 collagen expression in Wistar rats.

scholarly journals The retrospective study of 93 patients with transmigration of mandibular canine and a comparative analysis with a control group

2018 ◽  
Vol 41 (4) ◽  
pp. 390-396 ◽  
Author(s):  
Paweł Plakwicz ◽  
Joanna Abramczyk ◽  
Julita Wojtaszek-Lis ◽  
Jolanta Sajkowska ◽  
Barbara Warych ◽  
...  
Keyword(s):  
Contralateral Side ◽  
Permanent Teeth ◽  
Control Group ◽  
Study Group ◽  
Affected Side ◽  
Significant Difference ◽  
Mandibular Canine ◽  
And Control ◽  
Primary Canine

Summary Objectives The aim of this study was to evaluate characteristics of patients with unilateral transmigration of a mandibular canine in the largest study group presented until now. Materials and methods The study group consisted of 93 patients with unilateral transmigration of mandibular canine; the control group included 85 non-affected patients. Type of transmigration, status of deciduous and permanent canines, prevalence of missing teeth, class of occlusion, and space conditions were assessed to draw comparisons between groups. Results In this study, 64.5 per cent patients presented type 1 of transmigration; types 2, 3, 4, and 5 were present in, respectively, 23.7, 5.4, 4.3, and 2.1 per cent patients. There was a clear, statistically significant difference (P < 0.0001) between the mean crown and apex migration and angulation for the three groups of canines (transmigrated, contralateral, and control), whereas no differences were observed for the total number of permanent teeth present. In the study group, 73.1 per cent patients retained their primary canine on the affected side and 18.3 per cent on the contralateral side; in the control group, 22.3 per cent subjects had at least one primary canine. There was a statistically significant difference in the distribution of types of malocclusion between the study and the control groups. Conclusions Transmigration of mandibular canine was associated with the presence of retained primary canine on the affected side, higher mesial tilting of contralateral mandibular canine when compared to the canines in the control group. Additionally, higher prevalence of Angle’s Class I occlusion in patients with canine transmigration was recorded.

scholarly journals Taurine Attenuates Carcinogenicity in Ulcerative Colitis-Colorectal Cancer Mouse Model

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Guifeng Wang ◽  
Ning Ma ◽  
Feng He ◽  
Shosuke Kawanishi ◽  
Hatasu Kobayashi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Drinking Water ◽  
Mouse Model ◽  
Histopathological Examination ◽  
Tumor Formation ◽  
Water Model ◽  
Control Group ◽  
Ki 67

Taurine (2-aminoethane-sulfonic acid) is a type of amino acids and has numerous physiological and therapeutic functions, including anti-inflammation. However, there are few studies on the anticancer action of taurine. Our previous studies have demonstrated that taurine exhibits an apoptosis-inducing effect on human nasopharyngeal carcinoma cells in vitro. In this study, we have investigated whether taurine has an anticancer effect, using azoxymethane (AOM)/sulfate sodium (DSS)- induced mouse model for colon carcinogenesis. All mice, except those in control group, received a single intraperitoneal injection of AOM and DSS in the drinking water for 7 days twice, with 1-week interval. After the first DSS treatment, mice were given distilled water (model group) or taurine in the drinking water (taurine group) ad libitum. No tumor was observed in the control group. Taurine significantly suppressed AOM+DSS-induced tumor formation. Histopathological examination revealed AOM/DSS treatment induced colon cancer in all mice (8/8, 100%), and taurine significantly inhibited the progression of colon cancer (4/9, 44.4%). Taurine significantly attenuated cell proliferation in cancer tissues detected by Ki-67 staining. Taurine significantly increased the levels of an apoptosis marker cleaved caspase-9 and tumor suppressor protein PTEN. This is the first study that demonstrated that taurine significantly reduced carcinogenicity in vivo using AOM/DSS-induced colon cancer mouse model.

scholarly journals Sirolimus influence on hepatectomy-induced liver regeneration in rats

2014 ◽  
Vol 41 (3) ◽  
pp. 203-207 ◽  
Author(s):  
Edimar Leandro Toderke ◽  
Giorgio Alfredo Pedroso Baretta ◽  
Ozimo Pereira Gama Filho ◽  
Jorge Eduardo Fouto Matias
Keyword(s):  
Liver Regeneration ◽  
Negative Influence ◽  
Control Group ◽  
Cell Multiplication ◽  
Study Group ◽  
Adult Rats ◽  
Ki 67 ◽  
Immunohistochemical Markers ◽  
Significant Difference ◽  
And Control

OBJECTIVE: To evaluate the influence of sirolimus on liver regeneration triggered by resection of 70% of the liver of adult rats. METHODS: we used 40 Wistar rats randomly divided into two groups (study and control), each group was divided into two equal subgroups according to the day of death (24 hours and seven days). Sirolimus was administered at a dose of 1mg/kg in the study group and the control group was given 1 ml of saline. The solutions were administered daily since three days before hepatectomy till the rats death to removal of the regenerated liver, conducted in 24 hours or 7 days after hepatectomy. Liver regeneration was measured by the KWON formula, by thenumber of mitotic figures (hematoxylin-eosin staining) and by the immunohistochemical markers PCNA and Ki-67. RESULTS: there was a statistically significant difference between the 24h and the 7d groups. When comparing the study and control groups in the same period, there was a statistically significant variation only for Ki-67, in which there were increased numbers of hepatocytes in cell multiplication in the 7d study group compared with the 7d control group (p = 0.04). CONCLUSION: there was no negative influence of sirolimus in liver regeneration and there was a positive partial effect at immunohistochemistry with Ki-67.

scholarly journals Proliferation in Postmenopausal Endometrial Polyps—A Potential for Malignant Transformation

Medicina ◽  
2019 ◽  
Vol 55 (9) ◽  
pp. 543 ◽  
Author(s):  
Adomaitienė ◽  
Nadišauskienė ◽  
Nickkho-Amiry ◽  
Čižauskas ◽  
Palubinskienė ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Postmenopausal Women ◽  
Malignant Transformation ◽  
Hot Spot ◽  
Control Group ◽  
Ki 67 ◽  
Endometrial Polyps ◽  
Significant Difference ◽  
Immunohistochemical Studies ◽  
Asymptomatic Women

Background and objectives: Endometrial polyps in asymptomatic postmenopausal women are often incidentally found, yet only 1.51% of them are malignant. Their potential for malignant transformation has not been adequately addressed. The aim of this study was to investigate the proliferation within endometrial polyps as one of the indicators of their malignization potential in asymptomatic postmenopausal women. Materials and Methods: Immunohistochemical studies of Ki-67 were performed. Cases included 52 benign postmenopausal polyps, 19 endometrioid carcinoma with coexisting benign polyps, 12 polyps with foci of carcinoma and 4 cases of polyps, which later developed carcinoma. The control group included 31 atrophic endometria and 32 benign premenopausal polyps. Ki-67 was scored in either 10 or 20 “hot spot” fields, as percentage of positively stained cells. Results: The median epithelial Ki-67 score in postmenopausal benign polyps (4.7%) was significantly higher than in atrophic endometria (2.41%, p < 0.0001) and significantly lower than in premenopausal benign polyps (11.4%, p = 0.003) and endometrial cancer (8.3%, p < 0.0001). Where endometrial polyps were found in association with endometrial carcinoma, Ki-67 was significantly higher in cancer (p < 0.0001). No significant difference was found between Ki-67 scores of cancer focus and of the polyps tissue itself, respectively 2.8% and 4.55%, p = 0.37. Ki-67 expression, where polyps were resected and women later developed cancer, was not significantly different (p = 0.199). Conclusion: Polyps from asymptomatic postmenopausal women showed significantly more proliferation in both epithelial and stromal components than inactive atrophic endometria but less than premenopausal benign polyps and/or endometrial cancer. Benign postmenopausal endometrial polyps exhibit low proliferative activity, suggesting low malignant potential and may not require resection in asymptomatic women.

scholarly journals Association of Angiotensin I Converting Enzyme Insertion/287 bp Deletion Polymorphisms and Proliferative Prostatic Diseases among Lebanese Men

2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Asmahan A. El Ezzi ◽  
Jordan M. Clawson ◽  
Mohammed A. El-Saidi ◽  
Wissam R. Zaidan ◽  
Abigail Kovash ◽  
...  
Keyword(s):  
Allele Frequencies ◽  
Control Group ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Prostate Hyperplasia ◽  
Angiotensin I Converting Enzyme ◽  
Increased Risk ◽  
Significant Difference ◽  
Alu Repeat ◽  
Prostatic Diseases

Background. Angiotensin I converting enzyme (ACE) insertion (I) and 287 bp Alu repeat DNA fragment deletion (D) polymorphisms have been indicated in various cancers. Here, we investigated I/D polymorphisms in prostate cancer (PCa) and benign prostate hyperplasia (BPH) among Lebanese men. Methods. Blood DNA extracted from 69 control subjects, 69 subjects with clinically confirmed PCa, and 69 subjects with clinical BPH, all the subjects were aged 50 years or older, was subjected to the polymerase chain reaction. The PCR products were resolved in polyacrylamide gels to determine II, ID, and DD genotypes. The odds ratios (OR), 95% confidence intervals (CI), and p values of the allele frequencies and genotype ratios were calculated for establishing possible association of the alleles and/or genotypes and PCa and/or BPH. Results. The proportions of II, ID, and DD genotypes were significantly different from Hardy–Weinberg equilibrium for BPH and PCa groups (but not the control group), mostly due to overabundance of the ID genotypes. There was no significant difference in the I and D allele frequencies between the control groups and the affected groups. The ratio of (DD + ID)/II is significantly lower among the control group compared to the BPH group (RR = 8.92, p=0.042), and the ratio of ID/(DD + II) is significantly lower among the control group compared to the affected groups (RR = 1.99, p=0.021). Conclusions. Our data indicate that the D allele of the I/D polymorphisms of the ACE gene is associated with increased risk of BPH, and the ID genotype is a risk factor for both BPH and PCa among Lebanese males.

scholarly journals Effect of Amphotericin B and Micafungin Combination on Survival, Histopathology, and Fungal Burden in Experimental Aspergillosis in the p47phox−/− Mouse Model of Chronic Granulomatous Disease

2006 ◽  
Vol 50 (2) ◽  
pp. 422-427 ◽  
Author(s):  
Carly G. Dennis ◽  
William R. Greco ◽  
Yseult Brun ◽  
Richard Youn ◽  
Harry K. Slocum ◽  
...  
Keyword(s):  
Mouse Model ◽  
Chronic Granulomatous Disease ◽  
Amphotericin B ◽  
Fungal Infections ◽  
Rank Order ◽  
Granulomatous Disease ◽  
Knockout Mouse Model ◽  
Fungal Burden ◽  
Group I ◽  
Significant Difference

ABSTRACT Chronic granulomatous disease (CGD) is an inherited disorder of the NADPH oxidase characterized by recurrent life-threatening bacterial and fungal infections. We characterized the effects of single and combination antifungal therapy on survival, histopathology, and laboratory markers of fungal burden in experimental aspergillosis in the p47 phox − / − knockout mouse model of CGD. CGD mice were highly susceptible to intratracheal Aspergillus fumigatus challenge, whereas wild-type mice were resistant. CGD mice were challenged intratracheally with a lethal inoculum (1.25 × 104 CFU/mouse) of A. fumigatus and received one of the following regimens daily from day 0 to 4 after challenge (n = 19 to 20 per treatment group): (i) vehicle, (ii) amphotericin B (intraperitoneal; 1 mg/kg of body weight), (iii) micafungin (intravenous; 10 mg/kg), or (iv) amphotericin B plus micafungin. The rank order of therapeutic efficacy based on prolonged survival, from highest to lowest, was as follows: amphotericin B plus micafungin, amphotericin B alone, micafungin alone, and the vehicle. Lung histology showed pyogranulomatous lesions and invasive hyphae, but without hyphal angioinvasion or coagulative necrosis. Treatment with micafungin alone or combined with amphotericin B produced swelling of invasive hyphae that was not present in mice treated with the vehicle or amphotericin B alone. Assessment of lung fungal burden by quantitative PCR showed no significant difference between treatment groups. Serum galactomannan levels were at background despite documentation of invasive aspergillosis by histology. Our findings showed the superior efficacy of the amphotericin B and micafungin combination compared to either agent alone after A. fumigatus challenge and also demonstrated unique features of CGD mice as a model for experimental aspergillosis.

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