Effect of transient maternal hypotension on apoptotic cell death in foetal rat brain.

BACKGROUND: Intrauterine perfusion insufficiency induced by transient maternal hypotension has been reported to be associated with foetal brain malformations. However, the effects of maternal hypotension on apoptotic processes in the foetal brain have not been investigated experimentally during the intrauterine period. AIMS: The aim of this study was to investigate the effects of transient maternal hypotension on apoptotic cell death in the intrauterine foetal brain. STUDY DESIGN: Animal experimentation. METHODS: Three-month-old female Wistar albino rats were allocated into four groups (n=5 each). The impact of hypoxic/ischemic injury induced by transient maternal hypotension on the 15th day of pregnancy (late gestation) in rats was investigated at 48 (H17 group) or 96 hours (H19 group) after the insult. Control groups underwent the same procedure except for induction of hypotension (C17 and H17 groups). Brain sections of one randomly selected foetus from each pregnant rat were histopathologically evaluated for hypoxic/ischemic injury in the metencephalon, diencephalon, and telencephalon by terminal transferase-mediated dUTP nick end labelling and active cysteine-dependent aspartate-directed protease-3 (caspase-3) positivity for cell death. RESULTS: The number of terminal transferase-mediated dUTP nick end labelling (+) cells in all the areas examined was comparable in both hypotension and control groups. The H17 group had active caspase-3 (+) cells in the metencephalon and telencephalon, sparing diencephalon, whereas the C19 and H19 groups had active caspase-3 (+) cells in all three regions. The number of active caspase-3 (+) cells in the telencephalon in the H19 group was higher compared with the metencephalon and diencephalon and compared with H17 group (p<0.05). CONCLUSION: Our results suggest that prenatal hypoxic/ischemic injury triggers apoptotic mechanisms. Therefore, blockade of apoptotic pathways, considering the time pattern of the insult, may constitute a potential neuroprotective approach for the detrimental effects of prenatal hypoperfusion.

The therapeutic effects of melatonin and nimodipine in rats after cerebral cortical injury.

AIM: Secondary brain injury starts after the initial traumatic impact and marked by an increase in the intracellular calcium concentrations.This cascadeeventually results in membrane lipid peroxidation and neuronal cell death. MATERIAL AND METHODS: We investigated the neuro-protective effects of nimodipine and melatonin in 38 rats after 6 hours of head trauma using the cortical impact injury model of Marmarou. RESULTS: Brain water in the melatonin-given group decreased significantly comparing to that of control group the brain water in the nimodipine given group increased significantly comparing to that of trauma group. Histopathologically, brain edema was significantly low in melatonin-administered group comparing to that of control group while there were no changes in brain edema in the nimodipine given group and in the group that both nimodipine and melatonin were administered in combination. MDA levels in the brain tissues were significantly lower in the melatonin and nimodipine groups comparing to those of trauma and control group however this difference was by far significant in melatonin group comparing to nimodipine group. CONCLUSION: Melatonin appears to have neuro-protective effects on the secondary brain damage while nimodipine and nimodipine plus melatonin combination did not show such neuro-protective effects on the secondary brain injury.

In vitro growth stimulatory and in vivo wound healing studies on cycloartane-type saponins of Astragalus genus.

AIM OF THE STUDY: The present study was undertaken to evaluate the wound healing effects of the four chief saponins of Astragalus species [cycloastragenol (CA), astragaloside IV (AG), cyclocephaloside I (CCI) and cyclocanthoside E (CCE)]. MATERIAL AND METHODS: Effects of cell viability and proliferation of the isolated compounds were evaluated by the MTT assay on human keratinocyte. The wound healing activity was studied by using in vitro wound healing, proliferation and migration scratch assay. In order to see in vivo effectiveness of the compounds, an animal study with Sprague-Dawley male rats at the age of 12 weeks was carried out, and then the main histological outcomes were investigated to observe reepithelization, neovascularization, and presence of inflammatory cells, granulation tissue amount and maturation. RESULTS: All the compounds increased both fibroblast proliferation and migration, but the effects were much superior for CA at 1 ng/ml concentration. Among the compounds, based on the histological findings, 5% CA preparation was found to be the most remarkable in vivo wound healing agent showing greater cell density, more regularly organized dermis and more newly formed blood vessels. CONCLUSION: Results of this study indicate that the cycloartane-type saponins are the principal constituents responsible for wound healing activities of the roots of Astragalus species substantiating its use in traditional medicine.

Prenatal diagnosis of hemoglobinopathies in Hacettepe University, Turkey.

Between 1983 and 2008, prenatal diagnostic procedures for identifying hemoglobinopathies were performed in 947 at-risk fetuses. Seventy-six percent of the fetuses were at risk for ß-thalassemia major and 16% for sickle cell anemia; only a small percentage (7%) were at risk for compound heterozygosity of ß-thalassemia and an abnormal hemoglobin of the ß chain. The results of the study showed that ß gene mutations in hemoglobinopathies have a very broad spectrum. Seven hundred and thirty of the 947 fetuses examined using the DNA technique showed 88 different combinations of 27 different mutations. Although the number of fetuses evaluated was far below the desired target, the termination of 261 affected fetuses provided both psychological and economic relief for the parents and was economically beneficial for the country in the long term.

An immunohistochemical evaluation of cell adhesion molecules in human dental pulp after tooth preparation and application of temporary luting cements.

OBJECTIVE: The aim of this study was to determine if temporary luting cements used with provisional restorations alter the expression of cell adhesion molecules (CAMs) in human dental pulp. STUDY DESIGN: Twenty-five healthy human premolars and third molars scheduled to be extracted for orthodontic reasons were randomly assigned to 5 experimental groups. Group 1 included untreated teeth as negative control. In groups 2-5, provisional crowns were cemented to the prepared teeth with either eugenol-containing or eugenol-free temporary cement and extracted 24 or 48 h after the treatment. Expression ratio and staining intensity of CAMs, including E-selectin, P-selectin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and platelet endothelial cell adhesion molecule 1 (PECAM-1), was investigated in the pulp samples. The assessment of immunohistochemical reactions was performed by 2 independent observers using a semiquantitative scale. RESULTS: Significant reductions were recorded in the expression ratio and/or the staining intensity of E-selectin, ICAM-1, and VCAM-1 in samples removed 48 h after treatment with eugenol-containing cement compared with intact teeth. This reduction was significant only for ICAM-1 for 48-h eugenol-free samples. Moreover, the eugenol-free cement group indicated considerably higher E-selectin, ICAM-1, and VCAM-1 expression compared with the eugenol-containing group (P < .005) 48 h after the application. The PECAM-1 reactivity was similar for all of the experimental groups. CONCLUSION: Application of temporary luting cements after tooth preparation for full crown causes alterations in the expression of endothelial CAMs in the dental pulp.

Tezosentan attenuates organ injury and mesenteric blood flow decrease in endotoxemia and cecal ligation and puncture.

BACKGROUND: Decreased mesenteric blood flow and multiple organ injury due to free radicals are the consequences of septic shock. Since the blockade of endothelin receptors was reported to exert beneficial effects, we investigated the effects of tezosentan, a novel dual endothelin receptor antagonist, in two different experimental models of septic shock induced either by the injection of Escherichia coli endotoxin (ETX, 20 mg/kg, i.p.) or by cecal ligation and puncture (CLP). STUDY DESIGN: Swiss albino mice received tezosentan (10 mg/kg, i.p.) or its solvent saline (0.9% NaCl, w/v) twice at 2 and 22 h after ETX or CLP. At 24 h, the animals were anesthetized and the mesenteric blood flow was monitored for 15 min by using perivascular ultrasonic Doppler flowmeter. Then the animals were exsanguinated, and spleen, liver, and kidneys were isolated accordingly for histopathological examination. Thiobarbituric acid reacting substances and glutathione and myeloperoxides activities were also determined in the liver. RESULTS: In both ETX and CLP models, there was a decrease in mesenteric blood flow which was blocked by tezosentan. Similarly, tezosentan significantly attenuated the histopathological injury inflicted by both models. Although the glutathione levels were decreased and thiobarbituric acid reacting substances and myeloperoxidase activity were increased by ETX and CLP, tezosentan has failed to block these alterations in a consistent manner. However, a significant interaction between CLP and tezosentan with regard to myeloperoxidase activity and glutathione should be taken as partial evidence to explain the underlying mechanism of protection offered by tezosentan against liver injury. CONCLUSIONS: Therefore, we concluded that tezosentan, by working via mechanisms mostly other than the blockade of free radical induced damage, is a useful treatment option for combating the deleterious effects of septic shock such as mesenteric ischemia as well as liver, spleen, and kidney injury.

Immunohistochemical evaluation of endothelial cell adhesion molecules in human dental pulp: effects of tooth preparation and adhesive application.

OBJECTIVE: Studies have demonstrated that restorative procedures can initiate pulpal inflammation. Adhesion molecules on endothelial cells mediate the leukocyte-endothelium interaction, which is the fundamental event of inflammation. The aim of this study was to evaluate possible changes in the endothelial cell adhesion molecules (CAMs) of human dental pulp with tooth preparation, and after the application of one-step self-etch adhesive. MATERIALS AND METHODS: Twenty healthy human premolars and third molars scheduled to be extracted for orthodontic reasons were randomly assigned to four experimental groups. Group 1 involved sound intact teeth representing the controls. In group 2, teeth were prepared for full crown and extracted within 2h. Groups 3 and 4 comprised the teeth coated with one-step self-etch adhesive, iBond Gluma inside following the preparation and extracted after 24 and 48h, respectively. Tissue distribution and staining intensity of CAMs including E-selectin, P-selectin, ICAM-1, VCAM-1 and PECAM-1 was investigated in the pulp samples using monoclonal antibodies and the streptavidin-biotin-horse-radish immunoperoxidase procedure. The assessment of immunohistochemical reactions was performed by two independent observers using a semi-quantitative scale. RESULTS: All the CAMs evaluated were expressed by the healthy pulp tissues. Significant alterations in the distribution and staining intensity of CAMs were detected following tooth preparation. One-step self-etch adhesive tested in the present study induced inflammatory reactions in the pulp (P<0.05, Mann-Whitney U-test). CONCLUSION: It seems evident that tooth preparation for full crown and application of one-step self-etch adhesive on prepared teeth had a potential to interfere with the inflammatory response.

In vivo study to assess the viability and mass effect of fascia injection in comparison with block fascia graft.

Recently, fat injection has gained favor among plastic surgeons for soft tissue augmentation. However, fat injections lose 50% of their volume after 1 year. The profession is in need of an injectable bulking material that gives a long-lasting improvement. Using 30 male rats, this study investigated the stability of the size and structure of the injected fascia autograft and compared it with surgically transplanted fascia. The fascia graft was harvested from the back of the rat, big, and divided into two equal pieces. The first piece was minced into a paste and injected subcutaneously on the anterior surface of the right ear. The other piece was transplanted subcutaneously on the anterior surface of the left ear. The grafts were observed for any sign of resorption over 1 to 6 months.Grossly, injection and transplantation sites were palpable at the end of the observation periods. Microscopic examination showed that injected fascia maintains its histomorphologic structure. These findings indicate that the injected fascia graft is well tolerated, and the size of the graft remained stable. According to this study, fascia injection can result in bulking material that gives a long-lasting improvement, and can be a viable alternative to other methods.