The investigation of the antitumoral effect of Cornus mas L in mice with ehrlich solid tumor.

AIM: Cornus mas L is commonly used due to its anti-inflammatory, anti-carcinogenic and anti-oxidant properties. In the study, the effects of C. mas L extract on a solid tumor were examined in the Ehrlich solid tumor model developed in Balb/C type mice. METHODS: Ehrlich acid tumor (EAT) cells (1x106 EAT cell) from the stock animal were injected subcutaneously (s.c.) through the nape of the mice. Treatment groups of solid tumor-induced animals received 100 mg/kg and 200 mg/kg of C. mas L extract intraperitoneally (i.p.) for 14 days. RESULTS: Tumor volumes and animal weights were found to be statistically significant compared to the control group (p < 0.05). AgNOR staining was performed in tumor tissues. Statistically significant differences were observed between the groups in terms of TAA/NA ratio (p < 0.05). Immunohistochemical and biochemical parameters were also evaluated. An estimation of tumor proliferation of the lung, liver, brain, kidney, testis and tumor antioxidant parameters viz. lipid peroxidation, reduced glutathione (GSH), glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) was made. CONCLUSIONS: Our study showed that the anti-tumor effect of C. mas L in assisted tumor development with EAT cells, was mediated by the enhancement of oxidative stress with multiple mechanisms (Tab. 6, Fig. 12, Ref. 38).

The detection of curcumins' antitumoral effects via argyrophilic nucleolar organizing region-associated protein synthesis in mice with ehrlich's ascitic carcinoma.

BACKGROUND: Curcumin is a polyphenol compound that has antioxidant, anticancer, anti-inflammatory, anti-hyperlipidemic and antimicrobial effects. Nucleolar-organizing regions are the sites of the gene on chromosomes. The present study was aimed to show the antitumoral effect of curcumin via AgNOR protein synthesis in Ehrlich's ascitic carcinoma (EAC) bearing mice. METHODS: Twenty three mice with EAC were randomly divided into 3 groups as positive control (n = 7), group 2 (n = 8) and 3 (n = 8) treated intraperitoneally with curcumin (25 mg/kg) and (50 mg/kg), respectively. The animals were sacrificed on Day 16, the solid tumors were removed out. Then, total AgNOR area/nuclear area (TAA/NA) and the mean AgNOR number were estimated for each mice. RESULT: Statistically significant differences were determined among the whole groups for TAA/NA ratio (p = 0.000), conversely mean AgNOR number (p = 0.361). When comparingthe two groups; while no difference was determined between the control and curcumin (25 mg/kg) groups (p = 0.061), the significant differences were detected between the control and curcumin (50 mg/kg) groups (p = 0.000) and between curcumin (25 mg/kg) and curcumin (50 mg/kg) groups (p = 0.000) for TAA/NA ratio. However, there was no significant difference for the mean AgNOR number in double comparison of the groups. CONCLUSIONS: The current study showed that curcumin had a crucial function against cancer development. Also, both AgNOR values might be used as biomarkers for detection of the most reliable therapeutic dose selection of cancer treatment (Tab. 3, Fig. 2, Ref. 27).

Age-related changes of nasal cavity and conchae volumes and volume fractions in children: a stereological study.

BACKGROUND: The anatomy of the human nasal cavity (NC) is complex and its structures are closely related to the functions of the NC. Studies which assessing the mean volumes of NC and conchae are very infrequent. The purpose of current study is to investigate development of NC and conchae according to age and sex by using stereological method. MATERIALS AND METHODS: This retrospective volumetric study was carried out on 342 individuals (166 females and 176 males) between 0 and 18 years old with no pathological conditions or medical procedures that affected the skeletal morphology of the NC. Volumetric estimations were determined on computed tomography (CT) images using point-counting approach of stereological methods. RESULTS: NC, inferior nasal conchae (INC) and middle nasal conchae (MNC) volume measurements that obtained using point-counting method were increased with age in both sexes until 15 years old. Regardless of gender; no significant difference was determined between the left and right values for NC, conchae volumes and choanae measurements. Generally, significant differences were determined in NC and INC volumes according to gender after they reached maximum growth period. According to age the volume ratios of INC to NC and MNC to NC were ranged from 18% to 32% and 9% to15%, respectively. CONCLUSIONS: The current study demonstrated that the point-counting method is effective in determining volume estimation of NC and is well suited for CT studies. Our results could provide volumetric indexes for the NC and conchae, which could help the physician for both patient selections for surgery, and for the assessment of any surgical technique used to treatment of nasal obstruction. (.

The potential teratogenic effects of interferon beta-1a and interferon beta-1b on in vitro embryonic development.

BACKGROUND: Interferon beta (IFNb) was the first proven drug for the treatment of multiple sclerosis (MS). The diagnosis of MS frequently occurs in women at childbearing age (especially in twenties and thirties). Therefore, the pregnancy process is major concern for many women with MS. Data on women exposed to IFNb during pregnancy are limited. The aim of our study was to investigate the teratogenic potential of IFNb on embryonic development via embryo culture technique. Recently, this technique has been often used for determining teratogenic effect of pharmacologic drugs and potential teratogens on embryonic development. MATERIALS AND METHODS: In this study, IFNb was applied to the culture medium and after 48 h of culture effects of IFNbs (1000 IU/IFNb-1a and 1000 IU/IFNb-1b) on embryonic development were morphologically investigated. RESULTS: According to morphologic scoring system, total morphologic score, somite number and protein contents were similar between control group and two experimental groups (p > 0.05). On the other hand, yolk sac diameter, crown- -rump length and head length were significantly decreased in two experimental groups compared with control group (p < 0.05). CONCLUSIONS: Consequently, IFNb-1a and IFNb-1b, applied to the culture medium, have no macroscopic teratogenic effect on embryonic development. However, in respect of morphometric measurements, IFNb-1a and IFNb-1b have caused growth retardation in embryo. This research related to interferon was the first study using vitro embryo culture technique; thus, in our point of view, future studies which will be performed by using different doses of IFN will contribute to the literature.

Investigation of argyrophilic nucleolar organizing region.

BACKGROUND: Ischemia/reperfusion (I/R) injury is a complex event frequently observed in vascular surgery and can cause functional and structural cell damage. Nucleolar-organizing regions (NORs) are sites of the ribosomal genes located on chromosomes and can be stained with silver when they are active. Thus these proteins are named as argyrophilic-NOR (AgNOR)-associated proteins. We aimed to investigate any possible effects of renal I/R injury on the NOR protein synthesis and association between the AgNOR proteins amount and histopathological injuring score. METHODS: Nine female wistar-albino rats with weight of 200-250g were included into the study. The animals were randomly divided in two groups, a Control Group and an I/R Group. In I/R group, rats were subjected to 45 minutes of renal pedicle occlusion followed by 24 hours of reperfusion. In the control group no drug injections or ischemia reperfusion were performed in animals. Then histopathological injury score, mean AgNOR number and total AgNOR area/nuclear area (TAA/NA) were detected for each rat. RESULTS: The differences between control and I/R groups were significant for histopathological injury scores (p = 0.016). Also the differences between control group and I/R group were significant for mean AgNOR number (p = 0.000) and TAA/NA ratio (p = 0.000). Additionally, there was a positive correlation between TAA/NA ratio and histopathological injury score (r = 0.728; p = 0.026) and between mean AgNOR number and histopathological injury score (r = 0.670; p = 0.048). CONCLUSION: The detection of AgNOR proteins amount may be used as an indicator to obtain information about the cellular behaviour (self-protective mechanism of tubular epithelial cells) against I/R injury and cellular damage levels (Tab. 2, Fig. 4, Ref. 24).

May argyrophilic nucleolar organizing region-associated protein synthesis be used for selecting the most reliable dose of drugs such as rhamnetin in cancer treatments?

BACKGROUND: Rhamnetin is a flavonoid that has antioxidant, anti-inflammatory and anti-cancer effects. Nucleolar-organizing regions are the ribosomal genes region. We aimed to identify whether rhamnetin has an effect on cell proliferation and whether AgNOR proteins may be used for the detection of therapeutic benefits of the drugs and new metabolites, which have the potential of being used for cancer treatments. METHODS: Twenty-four mice with Ehrlich's ascites carcinoma (EAC) were randomly assigned to three main groups as positive control, and groups 2 and 3 treated intraperitoneally with rhamnetin (100 µg/kg and 200 µg/kg, respectively). All the animals were sacrificed on day16, 24 h after the last dose; the tumors, which developed at the site of injection were removed. Then, mean AgNOR number and total AgNOR area/nuclear area (TAA/NA) were detected for each mouse. RESULTS: Significant differences were detected among all groups for mean AgNOR number (p = 0.000) and TAA/NA ratio (p = 0.000). While the difference between positive control and Rhamnetin (100 µg/kg) group was not significant (p = 0.387), there are significant differences between positive control and Rhamnetin (200 µg/kg) group (p = 0.000) and between Rhamnetin (100 µg/kg) and Rhamnetin (200 µg/kg) groups (p = 0.000) for TAA/NA ratio. CONCLUSION: Rhamnetin has an important role in preventing cancer formation. Our study showed that mean AgNOR numbers and TAA/NA values may be used also as biomarkers for evaluating the success rate of the performed therapeutic strategy and accurate dose selection for the management of the disease (Tab. 3, Fig. 3, Ref. 45).

Estimation of spleen volume and surface area of the newborns' cadaveric spleen using stereological methods.

BACKGROUND: The purpose of this study was to compare different techniques for the estimation of spleen volume and surface area using magnetic resonance imaging (MRI) images, ultrasonography (USG) images and cadaveric specimen, and to evaluate errors associated with volume estimation techniques based onfluid displacement. MATERIALS AND METHODS: Five new born cadavers, aged 39.7 ± 1.5 weeks, weighted 2.220 ± 1.056 g, were included in the present study. Three different methods were used to assess the spleen volume. The vertical section technique was applied using cycloid test probes for estimation of spleen surface area in MRI. RESULTS: The mean ± standard deviation of spleen volumes by fluid displacement was 4.82 ± 3.85 cm³. Volumes determined by the Cavalieri's principle using physical section and point-counting techniques were 4.45 ± 3.47 cm³ and 4.65 ± 3.75 cm³, respectively; volumes measured by USG and cadaver using ellipsoid formula were 4.70 ± 3.02 cm3 and 5.98 ± 4.58 cm³, respectively. No significant differences were found among all methods (p > 0.05). The spleen surface area was calculated as a 32.3 ± 20.6 cm² by physical sections using cadaver and also it was determined on axial, sagittal and coronal MR planes as 24.9 ± 15.2 cm², 18.5 ± 5.92 cm² and 24.3 ± 12.7 cm², respectively. CONCLUSIONS: As a result, MR images allow an easy, reliable and reproducible volume and surface area estimation of normal and abnormal spleen using Cavalieri'sprinciple. We consider that our study may serve as a reference for similar studies to be conducted in future. :

Effect of interleukin 12 (IL-12) on embryonic development and yolk sac vascularisation.

BACKGROUND: In the recent days there has been an increase in diseases known as "angiogenic diseases" characterized by pathologic vascularisation. In the rat, the development of embryonic vessel starts to occur at 9.5 days of gestation. In mammals, the vascular system starts developing in a very early embryonic stage. The majority of rat embryo circulation system gets complete approximately at 11 - 12 days. Therefore the in vitro study of 9.5 - 11.5-day old embryo culture could be a suitable model to study the effects of angiogenic and antiangiogenic substances on yolk sac vascularisation. In the present study, the effects of Interleukin-12 (IL-12) on the yolk sac vascularisation are investigated during the in vitro embryo culture, where the latter angiogenic factor was added to serum. METHODS: After 48-hour culture period, effects of different doses of IL-12 (50 ng/ml, 100 ng/ml, and 200 ng/ml) were estimated morphologically. RESULTS: According to morphologic scoring system, the total morphologic score, yolk sac diameter, crown rump length, and somite number were retarded in all experimental groups when compared to control. These developmental retardations were statically significant. There was also a poor development in the yolk sac vascularisation and the heart. CONCLUSION: As a result, the IL-12 could cause developmental retardation of embryos owing to its antiangiogenic effect (Tab. 3, Fig. 2, Ref. 39).

Investigation of the effect of rhamnetin on mice injected with solid and ehrlich ascites tumor.

Rhamnetin is a flavonoid which contained in especially clove, such as apple, tea, and onion plant. Rhamnetin has been used in cancer research due to its antitumor and antioxidant properties. In this study, effects of rhamnetin administration at different doses on ascites and solid tumors were investigated in Balb/C mice bearing EAT model that originating from rat breast adenocarcinoma. Experimental procedure: Overall, 92 Balb-c mice were used in this study. EAT cells (1 × 106 cells) that harvested from stock animals were injected to all rats via intraperitoneal and subcutaneous route. Rhamnetin (100 µg/kg-200 µg/kg) were given intraperitoneally and subcutaneously during 10 and 15 days to the animals bearing ascites tumor and solid tumor, respectively. Throughout experiments, weight changes were recorded in all groups. The maximum weight increase was observed in the control group among all groups (ascites and solid tumor groups). In the treatment groups, the least weight increase were determined in 200-µg/kg rhamnetin applied. The lowest increase in tumor volume was observed in the group that received 200-µg/kg rhamnetin (2.84) when compared to tumor control group (3.67). Result and conclusion: We determined that the number of live and dead cells in the treatment groups administered with the mean rhamnetin dose (2.5 µg/ml) was found in the count made in the EAT cell line after the incubation periods. We observed that rhamnetin plays an important role against cancer formation. We have obtained important results in our study, but detailed studies on the relationship between rhamnetin and cancer are needed.

Optic nerve sheath diameter measurement: a means of detecting increased intracranial pressure in pseudotumor cerebri patients.

BACKGROUND: Pseudotumor cerebri (PTC) occurs when the pressure inside the skull increases for no obvious reason. The aim of this study was to investigate three different methods: the optic nerve sheath diameter (ONSD) method, ONSD/eyeball transverse diameter (ETD) index, and ONSD/orbital transverse diameter (OTD) index for the initial detection of elevated intracranial pressure in patients with PTC. MATERIALS AND METHODS: A retrospective study of magnetic resonance data from adult PTC patients (n = 42) and control group (n = 40) was performed. ONSD and OTD measurements were made 3 mm and 10 mm posterior to the globe, after intracranial pressure was measured with lumbar puncture. The sensitivity, specificity, and overall accuracy of the findings on magnetic resonance imaging were calculated. RESULTS: The optic nerve sheath was enlarged in the PTC group compared with the control group. It showed 97% sensitivity and 100% specificity and 79% sensitivity and 87.5% specificity for 3 mm and 10 mm, respectively. The ONSD/ETD and ONSD/OTD indices were increased in the PTC group compared with the control group. For 3 mm posterior to the globe, the ONSD/ETD index had 90.5% sensitivity and 92% specificity, and the ONSD/OTD index had 86% sensitivity and 95% specificity. For 10 mm posterior to the globe, the sensitivity and specificity of the ONSD/ETD and ONSD/OTD indices were 86% and 80% and 74% and 82.5%, respectively. CONCLUSIONS: According to our study, the ONSD method and the ONSD/ETD and ONSD/OTD indices are reliable diagnostic markers for PTC. These noninvasive techniques may be useful in monitoring the invasive intracranial catheter and have wide potential clinical applications in district hospitals, emergency departments and intensive care units.

Volumetric evaluation of hemicerebellar changes in migraine patients without aura.

Brain balance changes have been recognised in migraine, but cerebellar function between or during attacks has been assessed only in a few studies. Previous studies have indicated that migraine affects cerebellar function. In the present study we aimed to evaluate the hemicerebellar volume changes of patients with migraine without aura (MWoA). Volumetric changes of cerebellar hemispheres were evaluated in terms of asymmetry using stereological methods on magnetic resonance images (MRI) retrospectively. Nineteen patients with MWoA and 18 age- and gender-matched control subjects were included in the study. MRIs were analysed by using the point-counting approach of stereological methods by Cavalier's principle. There was no statistically significant cerebellar atrophy or hemicerebellar asymmetry between the MWoA and control subjects. There was no cerebellar atrophy or asymmetry between the MWoA and age-matched control group. The stereological evaluation of cerebellar asymmetry and atrophy in humans is important for both clinicians and anatomists. The technique is simple, inexpensive, and reliable.

The protective role of curcumin against toxic effect of nonylphenol on bone development.

INTRODUCTION: In the study, it was aimed to investigate the possible protective effects of curcumin, a potent antioxidant, against the toxic effect of nonylphenol on bone development. METHODS: Thirty pregnant female Wistar albino rats were used. The rats were randomly divided into the following five groups; the control group, corn oil group (150 µl/kg/day), nonylphenol group (50 µl/kg/day), curcumin group (100 mg/kg/day) and curcumin + nonylphenol group (100 mg/kg/day + 50 µl/kg/day). The doses were given by gavage from the 5th day to the 20th day of gestation. The fetuses were removed out on the 20th day of pregnancy by cesarean at the end of the study. After the sacrifice of the animals, double skeletal staining in front extremity (clavicula, scapula, humerus, radius, ulna) and hind extremity (femur, tibia, fibula), additionally histological and immunohistochemical examinations in femur bone were performed. RESULTS: The nonylphenol group offspring have the lowest weights of fetuses and placenta, head-to-hip lengths, biparietal and occipitofrontal length, and also, bone length percentage and percentage of the ossification area in all measurements of the front extremity and hind extremity Interestingly, the groups treated with curcumin showed close to the control group in terms of double skeletal staining, histological, and immunohistochemical examinations. CONCLUSIONS: Our findings demonstrated an association between bone development and exposure to nonylphenol. The findings suggest that curcumin treatments may be effective in accelerating bone formation.

The effect of diclofenac sodium on neural tube development in the early stage of chick embryos.

BACKGROUND: Neural tube defects are congenital malformations of the central nervous system. Genetic predisposition and some environmental factors play an important role in the development of neural tube defects. This study aimed to investigate the effects of diclofenac sodium on the neural tube development in a chick embryo model that corresponds to the first month of vertebral deve- lopment in mammals. MATERIALS AND METHODS: Seventy-five fertile, specific pathogen-free eggs were incubated for 28 h and were divided into five groups of 15 eggs each. Diclofenac sodium was administered via the sub-blastodermic route at this stage. Incubation was continued till the end of the 48th h. All eggs were then opened and embryos were dissected from embryonic membranes and evaluated morphologically and histopathologically. RESULTS: It was determined that the use of increasing doses of diclofenac sodium led to defects of midline closure in early chicken embryos. There were statistically significant differences in neural tube positions (open or close) among the groups. In addition; crown-rump length, somite number were significantly decreased in high dose experimental groups compared with control group. CONCLUSIONS: This study showed that development of neurons is affected in chi- cken embryos after administration of diclofenac sodium. The exact teratogenic mechanism of diclofenac sodium is not clear; therefore it should be investigated.

Examination of inclinations of the spine at childhood and adolescence.

BACKGROUND: Spine is a column that consists of consecutively lined up vertebras. It includes medulla spinalis. It contributes the motions of head, neck and body. Spine is not a straight column. There is a convexity towards the front of the spine (lordosis) at cervical and lumbar areas in adults and a convexity towards the back of the spine (kyphosis) at thoracic and sacral spine areas. MATERIALS AND METHODS: In this study, lateral magnetic resonance images of 731 children between 1 and 16 years of age were examined and their cervical lordosis, thoracic kyphosis and lumbar lordosis angles were measured with Cobb method using ImageJ programme for every age group. RESULTS: The mean calculated cervical lordosis angles in 1-16-year-old children were found to be 20.51o ± 6.11o (minimum 17.96o ± 6.29o, maximum 23.50o ± ± 4.14o). It has been observed that cervical angle values decrease with age. The mean thoracic kyphosis angle measured was 28.71o ± 6.99o (minimum 24.55o ± ± 5.65o, maximum 30.44o ± 4.68o). Lumbar lordosis angle was 28.08o ± 7.39o (minimum 20.36o ± 6.59o, maximum 32.68o ± 6.03o). Thoracic kyphosis and lumbar lordosis angle values increased with age. In our study, a statistical differ- ence was found in increasing thoracic kyphosis angle between 1-year-old group and 14-year-old group. Statistical difference was also found in decreasing cervical lordosis angle value between 1-year-old group and 16-year-old group. When we compare our study results with literature values, cervical lordosis values were similar, but lumbar lordosis values were lower. CONCLUSIONS: In summary, we think that knowing sagittal plane inclinations of the spine developing in childhood and adolescence will contribute to earlier de- termination of pathologies. We also hope that it will contribute to clinical stages and other studies in this field.

ETV5 cooperates with LPP as a sensor of extracellular signals and promotes EMT in endometrial carcinomas.

Endometrial carcinoma (EC) is the most frequent among infiltrating tumors of the female genital tract, with myometrial invasion representing an increase in the rate of recurrences and a decrease in survival. We have previously described ETV5 transcription factor associated with myometrial infiltration in human ECs. In this work, we further investigated ETV5 orchestrating downstream effects to confer the tumor the invasive capabilities needed to disseminate in the early stages of EC dissemination. Molecular profiling evidenced ETV5 having a direct role on epithelial-to-mesenchymal transition (EMT). In particular, ETV5 modulated Zeb1 expression and E-Cadherin repression leading to a complete reorganization of cell-cell and cell-substrate contacts. ETV5-promoted EMT resulted in the acquisition of migratory and invasive capabilities in endometrial cell lines. Furthermore, we identified the lipoma-preferred partner protein as a regulatory partner of ETV5, acting as a sensor for extracellular signals promoting tumor invasion. All together, we propose ETV5-transcriptional regulation of the EMT process through a crosstalk with the tumor surrounding microenvironment, as a principal event initiating EC invasion.

Effect of anti-basic fibroblast growth factor (anti-bFGF) on in vitro embryonic development in rat.

In this study, we aimed at the in vitro effects of anti-fibroblast growth factor-2 (anti-FGF-2 or anti-bFGF) on embryo culture in rats. In vitro effects of anti-bFGF on total embryonic development were investigated in 40 rat embryos (which were divided into four groups) (obtained from five pregnant females) at 9.5 days of gestation that were cultured in whole rat serum (WRS), and in WRS+ 2.5, 5, and 10 microg/ml anti-bFGF. After 48 h of culturing, the embryos from each group were harvested to be analysed morphologically according to a morphological scoring system and biochemically to obtain the embryo protein content. The morphological score, embryo protein content, somite number and crown-rump length of embryos indicated that embryos cultured in WRS+ anti-bFGF had significant embryonic retardation. Mean morphological scores for the embryos grown in WRS, in the presence of 2.5, 5 and 10 microg anti-FGF-2 were 61.4 +/- 1.64, 46.3 +/- 8.42, 27 +/- 2.58 and 13.6 +/- 0.96 respectively. These results suggest that bFGF is very important for normal embryonic development and rat anti-bFGF neutralizes bFGF effect.