Evaluation of volumetric asymmetry of the dorsolateral prefrontal cortex and medial temporal lobe in Alzheimer's disease using the atlas-based method.

Brain areas affected during neurodegenerative disease progression are considered anatomically connected to the first affected areas. The dorsolateral prefrontal cortex (DLPFC) has connections with the medial temporal lobe (MTL), which includes regions that become atrophic in Alzheimer's disease. In this study, we aimed to investigate the degree of volumetric asymmetry of DLPFC and MTL structures. This is a cross-sectional volumetric study involving 25 Alzheimer's disease patients and 25 healthy adults who underwent MRI with a 3D turbo spin echo sequence at 1.5 Tesla. The atlas-based method incorporated MRIStudio software to automatically measure the volume of brain structures. We compared the asymmetry index and volumetric changes across study groups and correlated them with Mini-Mental State Examination scores. We observed significant volumetric rightward lateralization in the DLPFC and superior frontal gyrus in Alzheimer's disease patients compared to the healthy controls. There was a significant volume loss in the MTL structures of Alzheimer's disease patients. Atrophy of MTL structures was positively correlated with right DLPFC volume changes in Alzheimer's disease patients. Volumetric asymmetry of the DLPFC may be a characteristic for determining disease progression in Alzheimer's disease patients. Future studies are recommended to evaluate whether these volumetric asymmetrical changes are specific to Alzheimer's disease and whether asymmetry measurements can serve as diagnostic markers.

Volume estimation of brain ventricles using Cavalieri's principle and Atlas-based methods in Alzheimer disease: Consistency between methods.

Automatic estimations of brain ventricles are needed to assess disease progression in neurodegenerative disorders such as Alzheimer Disease (AD). The objectives of this study are to evaluate the diagnostic performances of an automated volumetric assessment tool in estimating lateral ventricle volumes in AD and to compare this with Cavalieri's principle, which is accepted as the gold standard method. This is across-sectional volumetric study including 25 Alzheimer patients and 25 healthy subjects undergoing magnetic resonance images (MRI) with a 3D turbo spin echo sequence at 1.5 Tesla. The Atlas-based method incorporated MRIStudio software to automatically measure he volumes of brain ventricles. To compare the corresponding measurements, we used manual point-counting and semi-automatic planimetry methods based on Cavalieri's principle. Bland-Altman test results indicated an excellent agreement between Cavalieri's principle and the Atlas-based method in all volumetric measurements (p < 0.05). We obtained a 64% sensitivity and 92% specificity for lateral ventricular volumes according to the Atlas-based method. AD subjects had significantly larger left and right lateral ventricle volume (LVV) when compared to control subjects in respect to three volumetric methods (p < 0.01). Lateral ventricle-to-brain ratio (VBR) statistically increased 49.23% in measurements done with the point-counting method, 45.12% with the planimetry method, and 45.49% with the Atlas-based method in AD patients (p < 0.01). As a result, the Atlas-based method may be used instead of manual volumetry to estimate brain volumes. Additionally, this method provides rapid and accurate estimations of brain ventricular volumes in-vivo examination of MRI.

The protective effect of curcumin administration on carbon tetrachloride (CCl4)-induced nephrotoxicity in rats.

BACKGROUND: The aim of the present study was to examine the protective effect of curcumin (CUR) on carbon tetrachloride (CCl4)-induced nephrotoxicity to evaluate the detailed mechanisms by which CUR exerts its protective action. METHODS: Thirty male Wistar-Albino rats weighing 250-300 g were randomly divided into three groups: administrations of olive oil (control, po), CCl4 (0.5mg/kg in olive oil sc) every other day for 3 weeks, and CCl4 (0.5mg/kg in olive oil sc) plus CUR (200mg/kg) every day for 3 weeks. RESULTS: Administration of CCl4 significantly (p<0.001) increased the levels of renal function test such as creatinine and blood urea nitrogen (BUN). Furthermore, treatment of CCl4 significantly elevated the oxidant status of renal tissues while decreasing its anti-oxidant status (p<0.001). CUR displayed a renal protective effect as evident by significant decrease in inflammation and apoptosis during histopathological examination. The administration of CCl4 resulted in an increase in malondialdehyde (MDA) production due to an increase in membrane lipid peroxidation; however, the administration of CUR attenuated this, probably via its antioxidant and free radical scavenging properties. CONCLUSION: The finding of our study indicates that CUR may have an important role to play in protecting the kidney from oxidative insult.

Effects of melatonin hormone on hippocampus in pinealectomized rats: an immunohistochemical and biochemical study.

OBJECTIVE: The effects of melatonin on antioxidant status were examined in pinealectomized rats using enzymatic, histological and immunohistochemical techniques. The aim of this study is to investigate the effects of melatonin on hippocampal apoptosis. MATERIALS AND METHODS: Male Wistar rats (n=21) were divided into 3 groups: Group I and group II were designated as control (sham-pinealectomy) and pinealectomized rats, respectively. Rats in group III were pinealectomized and injected daily with melatonin (1 mg/kg) for 3 months beginning at day 7 after surgery. At the end of experimental period, all rats were killed by decapitation. The brains of the rats were removed and the hippocampus tissue was obtained from all brain specimens. The right hippocampal specimens of all rats were used for determination of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels. The left hippocampus tissue specimens of all animals were used for immunohistochemical and histological evaluation. RESULTS: The levels of SOD and GSH-Px were significantly decreased, and MDA levels were significantly increased in pinealectomized rats compared to the controls. In the histological and immunohistochemical evaluation of this group, increase of pyknotic cells, vacuolar degeneration and apoptosis were observed. However, increased SOD and GSH-Px enzyme activities, and decreased MDA levels were detected in the rats administered melatonin after pinealectomy. Furthermore, histological and apoptotic changes in hippocampus caused by pinealectomy were lost in the rats treated with melatonin. CONCLUSIONS: The results of our study revealed that pinealectomy-induced oxidative damage and morphological changes in the hippocampal tissue were suppressed by melatonin.

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) (20 mg/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.

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 25-30 g and 8 weeks of age, were used. Twenty of the mice were treated with DMH subcutaneously (20 mg/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 (20 µg/mouse) intraperitoneally and then subcutaneously every 48 h (5 µg/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.

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 µg 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.

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 25mg/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. This study has documented that intraperitoneal usage of the pheytoin during pregnancy may cause to different skeletal malformations, even with lower doses, in rat fetuses.