Adverse effects of maternal retinyl palmitate, a vitamin A compound, on the fetal liver.

Background: Consuming high doses of vitamin A during pregnancy may lead to malformations in the offspring. Some reports state that low doses that do not cause macroscopic abnormalities may result in mental and behavioral disorders. However, there are few studies on the microscopic effects of these doses on the organism. Objective: The aim was to investigate the effects of early prenatal exposure to different doses of oral vitamin A on the fetal liver. Materials and methods: Twenty-five pregnant rats, divided into five groups, received oral vitamin A at doses of 10,000, 50,000, 100,000, and 200,000 IU/kg between days 10 and 12 of gestation. The fetuses were collected on day 19 of gestation, their livers were dissected, and histology, apoptosis, and proliferation were examined by hematoxylin-eosin, TUNEL assay, and Ki67 immunolabeling using stereological methods. Results: Vitamin A decreased fetal liver volume, the number of Ki67-positive cells per unit volume, and the total number of hepatocytes at all doses except 10,000 IU/kg (p<0.001). Consequently, apoptosis was significantly higher in the groups receiving 100,000 and 200,000 IU/kg vitamin A (p<0.001). Conclusion: Our study shows that vitamin A administered during gestation days 10-12 has a suppressive effect on the developing rat liver when the dose exceeds 10,000 IU/kg, probably due to increased apoptosis and suppressed cell division.

Autonomic reflex effect of the inferior turbinate outfracture or bipolar cauterization inferior turbinate reduction surgery.

PURPOSE: To compare the autonomic reflexes caused by inferior turbinate outfracture or bipolar cauterization for inferior turbinate reduction surgery. METHODS: The investigators designed and implemented a prospective study composed of 80 patients who underwent a septoplasty with inferior turbinate reduction. The predictor variable was the type of bilateral reduction operation and included inferior turbinate outfracture with a freer elevator and 20 watts bipolar cauterization for 15 s per side after septoplasty. The primary outcome variable was the intraoperative changes of the heart rate monitored preoperatively and 20 s, 1 min, and 4 min after the turbinate reduction procedure. Other variables were systolic and diastolic blood pressure alterations after the inferior turbinate outfracture or bipolar cauterization procedure. Descriptive and bivariate statistics were computed and the P-value was set at .05. RESULTS: The sample was composed of 160 procedures in 80 patients grouped as follows: Outfracture (n = 100) and Cauterization (n = 60). There were no significant differences between the ages; grades of the turbinate hypertrophy; preoperative heart rates; and intraoperative 4th-minute heart rates, systolic and diastolic blood pressures. However, baseline systolic (p < 0.001) and diastolic (p < 0.001) blood pressures of the bipolar cauterization group were higher than outfracture group. Bipolar cauterization did not cause any significant changes in the heart rate, systolic and diastolic blood pressures. Inferior turbinate outfracture procedure caused a significant increase in heart rate (65.4 ± 9.82, p < 0.001), systolic (103 ± 8.62, p < 0.001) and diastolic (63.5 ± 7.37, p < 0.001) blood pressures. CONCLUSION: The results of this study suggest that during the inferior turbinate outfracture procedure, it is important to closely monitor sympathetic and parasympathetic reflexes. The surgeon, and anesthesiologist, must be aware of the early stages of the autonomic reflexes during turbinate reduction.

A New Perspective in Comparing Injuries Caused by Short-Duration External and Internal Forces in Saphenous Vein.

BACKGROUND: Great saphenous vein (GSV) graft failure is one of the major reasons for repeat bypass grafting. A comparison of the effects of simultaneous, short-duration, externally squeezing and internally distending forces on the same segment of ex-vivo human GSV has not yet been published, although similar studies have compared the experimental injury of different ex-vivo human veins. METHODS: Approximately 8-cm-long segments of GSV were harvested from each of the 15 patients. For each specimen, one end of the vein piece was occluded at a distance of 1 cm with an external cross-clamp for 5 min and the other end was similarly occluded at a distance of 1 cm by an endoluminal balloon. The middle sections of the veins, which were not occluded by any means, were taken as the control group. Two histologists, who were blinded to the groups, graded the hematoxylin and eosin (H&E) and Weigert-Van Gieson (WVG) stained sections semi-quantitatively and performed the histomorphometric measurements. RESULTS: The result of the histopathological evaluation of the intima layer showed that the microscopic scoring of lesions in the balloon group was significantly higher than that in the clamp and control groups (5.16 ± 1.32, 3.83 ± 0.75, and 1.00 ± 1.09, respectively; P < .001). In the adventitia layer, this level of scoring increased more in the clamp group than in the balloon and control groups (5.16 ± 1.16, 3.00 ± 0.89, and 0.16 ± 0.40, respectively, P < .001). CONCLUSION: Both the endoluminal balloon and external clamp techniques have harmful effects on the vein wall. Studying different kind of forces on different veins cannot provide us with reliable comparisons.

Can a Small Intestine Segment Be an Alternative Biological Conduit for Peripheral Nerve Regeneration?

BACKGROUND: Autologous nerve grafts are used to bridge peripheral nerve defects. Limited sources and donor site morbidity are the major problems with peripheral nerve grafts. Although various types of autologous grafts such as arteries, veins and muscles have been recommended, an ideal conduit has not yet been described. AIMS: To investigate the effectiveness of a small intestinal conduit for peripheral nerve defects. STUDY DESIGN: Animal experimentation. METHODS: Twenty-one rats were divided into three groups (n=7). Following anaesthesia, sciatic nerve exploration was performed in the Sham group. The 10 mm nerve gap was bridged with a 15 mm ileal segment in the small intestinal conduit group and the defect was replaced with orthotopic nerve in autologous nerve graft group. The functional recovery was tested monthly by walking-track analysis and the sciatic functional index. Histological evaluation was performed on the 12th week. RESULTS: Sciatic functional index tests are better in autologous nerve graft group (-55.09±6.35); however, during follow-up, progress in sciatic functional index was demonstrated, along with axonal regeneration and innervation of target muscles in the small intestinal conduit group (-76.36±12.08) (p<0.05). In histologic sections, distinctive sciatic nerve regeneration was examined in the small intestinal conduit group. The expression of S-100 and neurofilament was observed in small intestinal conduit group but was less organised than in the autologous nerve graft group. Although the counted number (7459.79±1833.50 vs. 4226.51±1063.06 mm2), measured diameter [2.19 (2.15-2.88) vs. 1.74 (1.50-2.09) µm] and myelin sheath thickness [1.18 (1.09-1.44) vs. 0.66 (0.40-1.07) µm] of axons is significantly high in the middle sections of autologous nerve graft compared to the small intestinal conduit group, respectively (p<0.05), the peripheral nerve regeneration was also observed in the small intestinal conduit group. CONCLUSION: Small intestinal conduit should not be considered as an alternative to autologous nerve grafts in its current form; however, the results are promising. Even though the results are no better than autologous nerve grafts, with additional procedures, it might be a good alternative due to harvesting abundant sources without donor site morbidity.

A new apparatus for standardization of experimental burn models.

BACKGROUND: Burns have severe economic burden for families and countries therefore its treatment modalities have utmost importance. Several study both experimental or clinic has been reported accordingly. Although contact burns were frequently used models, most of them were manually designed. The elapsed time was recorded only. However, the real time contact surface temperature (T) and weight force (WF) were fundamental characteristics of a burn model. The aim of this study is to create a standard burn model with recording real time variables on behalf of custom designed apparatus. METHODS: A custom designed apparatus was manufactured in which the variables of real time T, WF and elapsed time could be set and record. A vertical angle was provided to ensure the applied WF. And hence, Sprague-Dawley rats were randomly divided into four groups: (1) Burned at 60±1°C with low WF(G60WFL), (2) Burned at 60±1°C with high WF(G60WFH), (3) Burned at 80±1°C with low WF(G80WFL), (4) Burned at 80±1°C with high WF(G80WFH). The healthy skin thickness and burn depth were measured. The percentage of burn depth to healthy skin was used for statistical analysis. RESULTS: Constant variables T and WF were achieved. The pressure applied on skin was not significant between low [G60WFL vs G80WFL, (p=0.1704)] and high [G60WFH vs G80WFH (p=0.2369)] WF groups. However the percentage of burn depth was increasing owing to applied WF in 60°C group [G60WFL vs G60WFH, (p=0.0125)] and in 80°C group [G80WFL vs G80WFH (p<0.0001)]. And also the percentage was significantly increasing owing to set T, in low WF group [G60WFL vs G80WFL (p<0.0001)] and high WF group [G60WFH vs G80WFH (p<0.0001)]. Besides neither T nor WF has priority. CONCLUSION: Without recording the real time T and WF, it is infeasible to achieve a standard burn model. For a standard depth of burn, variables should be under control, as if our custom designed apparatus.

Nerve Tissue Prefabrication Inside the Rat Femoral Bone: Does It Work?

AIM: To investigate whether nerve regeneration can be induced in the tubular bone between distal and proximal cut nerve ends. MATERIAL AND METHODS: Twenty adult Wistar rats were used for the study. Rats were divided into three groups; femoral bone conduit group, nerve transection group, sham group. The sciatic nerve was surgically cut and from both ends inserted into the adjacent femoral bone tunnel in the femoral bone conduit group. The sciatic nerve was cut transversely in the nerve transection group. In the Sham group, only sciatic nerve exploration was performed, without a nerve cut. The groups were evaluated functionally and morphologically. RESULTS: All results showed that axonal growth existed through the osseous canal. CONCLUSION: To the best of our knowledge, this is the first study to evaluate neural regeneration inside the bone. We can speculate that the bone marrow provides a convenient microenvironment for peripheral nerve regeneration. In addition to prefabricating peripheral nerves, this novel model may help to establish further strategies for engineering of other tissues in the bone marrow.

Gender- and anxiety level-dependent effects of perinatal stress exposure on medial prefrontal cortex.

Early life stress leads to psychopathological processes correlated with the predisposition of individuals. Prolonged development of the prefrontal cortex (PFC), playing a critical role in the cognition, personality and social behavior, makes it susceptible to adverse conditions. In this study, we evaluated the dendritic morphology of medial PFC neurons in rats subjected to perinatal stress exposure. Unbiased stereological counting methods showed that total number estimation of c-Fos (+) nuclei, indicating the neuronal activation upon stressful challenge, significantly increased in high anxious animals compared with low anxious and control groups, in both gender. Golgi-Cox staining of neurons displayed anxiety level- and sex-dependent reduction in the dendritic complexity and spine density of pyramidal neurons, especially in the stressed males. While the total length of dendrites were not correlational; density of spines, specifically the mushroom subtypes, showed a negative correlation with the anxiety level of stressed animals. These results suggest that medial PFC is a critical site of neural plasticity within the stressor controllability paradigm. Outcomes of early life stress might be predicted by analyzing the density and morphology of spines in the apical dendrites of pyramidal neurons in correlation with the anxiety-like behavior of animals.

Effects of long-term agomelatine treatment on the cognitive performance and hippocampal plasticity of adult rats.

Agomelatine is an antidepressant with a distinct pharmacological mechanism of action as an MT1 and MT2 receptor agonist and as a 5-HT2C receptor antagonist. We evaluated the chronic effects of agomelatine administration (40 mg/kg, 20 weeks) on the cognitive performance of rats in the Morris water maze task. We applied unbiased stereological quantification methods to estimate the total numbers of granular and pyramidal neurons located in the dorsal hippocampus. We also analyzed the dendritic spines of pyramidal neurons in the CA1 region using the Golgi-Cox impregnation method. The agomelatine-treated group found the hidden platform more quickly than did the control group and spent significantly more time in the target quadrant. Agomelatine administration caused significant volumetric and numerical enhancements in granular and pyramidal neurons in the dentate gyrus and CA1-3 subregions, respectively. Increased densities of the mushroom and stubby types of spines, with no alteration in the thin-shaped spines, were observed in the agomelatine-treated group. These results showed that long-term agomelatine administration induced a nootropic effect supported by structural changes. Enhancement of the more stable types of dendritic spines might indicate improved adaptive capacity in hippocampal neurons. Future studies will provide a better understanding of the effect of this drug on synaptic plasticity.