Effects of intraperitoneal administration of the phenytoin on the skeletal system of rat fetus

This study was conducted on determining the effects of phenytoin on the skeletal system of the fetuses of 13 Wistar Albino rats. The female rats were divided into two groups after the vaginal smear test: the group 1 (control group) included 6 individuals, whereas the group 2 (phenytoin group) comprised 7 animals. A dose of 25 mg/kg/day phenytoin was administered intraperitoneally to pregnant rats on the 8th-10th days of pregnancy and fetuses were obtained by C-section on the 20th day. A number of 82 fetuses were observed by double staining technique. Their lengths and weights were measured, revealing the statistically significant differences between the two groups (p < 0.001). The lengths of the fetuses in the group 2 were determined as to be 14% shorter and the weights 13% lower compared to those in the group 1. Similarly, number of the fetuses obtained in one gestation decreased 9% in the group 2. Ossification of the skull bones in the fetuses of the group 2 was observed eminently to be deteriorated through using dissection microscope and inspection. Costal separation anomaly was observed in the 10 fetuses of the group 2. The separated-laterally located costal components were not attached to the costal arch. Shape malformations in the last two ribs and wide angularity, particularly in the last six ribs, were also determined

Effect of endostatin on 1,2-dimethylhydrazine-induced colon tumor in mice

Endostatin, one of the most potent negative regulators of angiogenesis, is naturally occurring as an inhibitor of angiogenesis capable of inhibiting tumor growth and their metastases. We aimed to investigate the in vivo activities of low dose of recombinant human endostatin on 1,2-dimethylhydrazine (DMH)-induced mice colon cancer. Thirty male Balb-c mice were injected with DMH (20 mg/kg/week) subcutaneously once a week for 12 weeks to induce colon cancer. Twelve weeks after the last DMH injection, 7 mu g rh-endostatin was injected every day for 6 weeks. The animals were killed after 30 weeks for histopathological examination. The weight of the animals, tumor inhibition rates, death rates and the distribution of the lesions in colon were evaluated after the mice were killed. The mean colonic lesions incidence in single tumor bearing mice was 11 +/- 4.0 in those treated with DMH and 8.1 +/- 3.7 in those treated with endostatin. When we look at the distribution of lesions in the colon, they occurred in the distal colon. At the end of our study, we noticed that the number of lesions decreased by 25% in the group of endostatin, considering the number of the lesions in the group of DMH. But there was no statistical difference between the mice treated with endostatin and those treated with DMH. It will be very significant to identify endostatin therapeutic effects as long as proper dose of endostatin is administrated at the proper time, duration and proper tumor model

Effect of angiostatin on 1,2-dimethylhydrazine-induced colon cancer in mice

Antiangiogenic therapy is supposed to be an attractive approach for antitumor treatment. Human plasminogen-derived angiostatin K1-3 is one of the most potent antiangiogenic agents known currently. However, it is unclear whether angiostatin has got protective effects on colon cancer. So we investigated the protective effects of angiostatin on 1,2-dimethylhydrazine (DMH)-induced colon cancer in mice. Thirty Balb/C male mice, weighing 25-30g and 8 weeks of age, were used. Twenty of the mice were treated with DMH subcutaneously (20mg/kg) once a week for 12 weeks. Six mice died during the DMH injection and surviving mice were divided into two groups (7 mice in DMH and 7 mice in DMH+angiostatin groups). In the angiostatin group, 6 weeks after the last DMH injection the animals were first treated with angiostatin (20g/mouse) intraperitoneally and then subcutaneously every 48h (5g/mouse) throughout a period of 12 weeks. The animals were killed after 30 weeks for histopathological examination. When we look at the distribution of lesions in the colon, they mainly occurred in the distal colon. The incidence of mean colonic lesions in a tumor-bearing mouse was 9.85 +/- 4.91 in those treated with DMH and 8.71 +/- 3.49 in those treated with angiostatin. The incidence of colon tumors was not significantly affected by low dose of angiostatin, and we noticed that the number of lesions decreased by 12% in DMH+angiostatin group compared to the number of the lesions in DMH group, but this decrease was not statistically significant (p>0.05). The administration period of angiostatin corresponds to the precancerous period and the reduction in the number of lesions could be important for the protective function of angiostatin in DMH+angiostain group. We assume that therapeutic effects of angiostatin are related to its doses, route of administration, frequency and administration period. In addition, we believe that combination of high doses of angiostatin with radiation, gene therapy or chemotherapy might be successful in proper tumor model

Effects of Angiostatin on in vitro Embryonic Rat Development

The progression of angiogenesis is controlled by a delicate balance between the positive and negative regulators. Angiostatin has potent antiangiogenic effect on endothelial cells, influencing their proliferation, differentiation and other functions. In this study, in vitro effects of angiostatin on total embryonic growth were investigated in rat embryos. The rat embryos were explanted on day 9.5 and cultured in whole rat serum (WRS) (for control) and adding 0.5, 2.5 and 5 mu g/ml angiostatin (for experimentals) in WRS. After 48 hours culture period, the embryos from each group were harvested and analysed morphologically. The results showed that the embryonic growth and development during organogenesis decreased in the presence of angiostatin when compared to embryos grown in WRS. Mean morphological scores for the embryos grown in WRS and in the presence of 0.5, 2.5 and 5 mu g/ml angiostatin were 59.8 +/- 2.02, 34.8 +/- 8.52, 22.4 +/- 6.41 and 17.8 +/- 6.19, yolk sac diameters were 6.0 +/- 0.2, 4.8 +/- 0.55, 4.5 +/- 057 and 4.2 +/- 0.39 mm, crown-rump lengths were 5.4 +/- 0.23, 4.4 +/- 0.42, 4.1 +/- 0.87 and 3.7 +/- 0.51 mm and mean protein contents of embryos were 140.76 +/- 12.21, 112.66 +/- 8.67, 89.85 +/- 10.89 and 53.77 +/- 8.15 mu g/ml respectively. Median value of the somite numbers was 24 (24-25) in control group and it was diminished 14 (1214), 12 (11-17) and 13 (8-17) respectively in experimental groups. As a result the angiostatin could cause developmental retardation of embryo because of its antiangiogenic effect

Influence of gilaburu (Viburnum opulus) juice on 1,2-dimethylhydrazine (DMH)-induced colon cancer

In this study, the effects of gilaburu (Viburnum opulus) juice on colon tumorogenesis were investigated. Eight weeks old Balb-C male mice received subcutaneous injections of 1,2-dimethylhydrazine (DMH) (20mg/kg body weight) once a week for 12 weeks. Both the sham control (group 1) and the DMH control (group 2) groups received drinking water alone, whereas the mice of groups 3 and 4 received gilaburu juice for 30 weeks (started with first DMH injection) and for 18 weeks (started after last DMH injection), respectively. Eighteen weeks after the last DMH injection, all mice were killed and the histogenesis of colon tumors was investigated from the paraffin-embedded sections of colon, which were stained with hematoxylin-eosin. The sites and incidences of tumoral lesions (low-grade dysplasia, high-grade dysplasia, intramucosal carcinoma and invasive carcinoma) were analyzed and compared with control. The results showed that the body weights of the mice were similar in all the groups. No tumoral lesions were found in group 1. Colon tumors developed in all DMH-treated mice (groups 2, 3 and 4). In these groups, the greatest numbers of tumor lesions were detected in the distal colon, followed by the mid-colon and only a few in the proximal colon. There was a reduction in the mean total number of tumor lesion in groups 3 (8.5) and 4 (8.3), when compared to group 2 (11.3). The incidence of invasive carcinoma in group 3 was significantly lower than group 2 (p<0.05). On the basis of these results, we conclude that gilaburu juice may be useful for the prevention of colon cancer at the initiation stage

Does drug compliance change in asthmatic patients during pregnancy?

BACKGROUND: Pregnant women with asthma are recommended to maintain optimal therapeutic management during pregnancy. Uncontrolled, symptomatic asthma may increase the risk of adverse peri-natal outcomes; thus adequate regular anti-asthmatic treatment must be given to provide optimal asthma control during pregnancy. However, doubts about the safety of asthmatic drugs can affect pregnant asthmatic patients’ drug compliance. The aim of this study was to assess behavioral differences in drug compliance among pregnant asthmatic patients. METHODS: Thirty two asthmatic and 121 healthy pregnant women were enrolled in the study. Structured face-to-face interviews were conducted after delivery. The interviews included disease characteristics, drug compliance and patients’ own perspective for asthma status prior to and during pregnancy. In addition, medical and pregnancy history, pregnancy complications and outcomes, and newborn characteristics were recorded. RESULTS: In our study group the rates of hospitalization, emergency room visits and systemic steroid use in the year before pregnancy were 13%, 46.9% and 18.8%, respectively. The rate of regular asthma medication use was only 32% at that period and increased to 44% during pregnancy. However, hospitalization, emergency room visits, systemic steroid usage rates remained unchanged and according to patients’ own evaluations, 44% of asthmatics pointed out that their asthma had worsened during pregnancy. No statistically significant difference was detected in terms of pregnancy/labour complication between asthmatic and non-asthmatics. CONCLUSIONS: Contrary to some previous studies, in our study regular use of asthma drugs increased during pregnancy. The uncontrolled condition of their asthma before and during pregnancy and the idea that their asthma worsened during pregnancy might force the patients to use medication more regularly

Safety of once-or twice-daily dosing of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with nonvalvular atrial fibrillation: A NOAC-TR study

WOS: 000433285000010PubMed ID: 28968197Once-daily dosing of non-vitamin K antagonist oral anticoagulants (NOACs) may increase patient adherence to treatment but may also be associated with a higher risk of bleeding. In this study, we investigated the adherence to once-or twice-daily dosing of NOACs and the risk of bleeding in nonvalvular atrial fibrillation (NVAF) patients. This multicenter cross-sectional study, conducted between 1 September 2015 and 28 February 2016, included 2214 patients receiving NOACs for at least 3 months, due to NVAF. Patients receiving once-daily or twice-daily NOAC doses were 1: 1 propensity score matched for baseline demographic characteristics and the presence of other diseases. The medication adherence was assessed by the 8-item Morisky Medication Adherence Scale. Risk factors were investigated in relation to minor and major bleeding. The mean age of patients was 71 +/- 10 years, and 53% of the patients were women. The medication adherence was lower in patients receiving twice-daily NOAC doses compared to once-daily-dose group (47% versus 53%, p = 0.001), and there was no difference between the groups in terms of minor (15% versus 16%, p = 0.292) and major bleeding (3% versus 3%, p = 0.796). Independent risk factors for bleeding were non-adherence to medication (OR: 1.62, 95% CI: 1.23-2.14, p = 0.001), presence of 3 or more other diseases (OR: 10.3, 95% CI: 5.3-20.3, p < 0.001), and HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile INR, Elderly, Drugs or alcohol) score (OR: 4.84, 95% CI: 4.04-5.8, p < 0.001). In summary, the once-daily dose of NOACs was associated with increased patient adherence to medication, while it was not associated with bleeding complications