Myelin Ultrastructure Terminology in Disease and Recovery Processes.

Ultrastructural evaluation of myelin coat helps to understand the possible background of pathological changes leading to deterioration or complete loss of nerve functions. A number of terms were previously introduced to describe the fine structural changes in myelin under various conditions. We believe that using a common terminology will be helpful to interpret the structure/function relationship in neurological disorders empowering the diagnosis and possible therapeutical approaches. In this paper, we present examples of ultrastructural changes in myelin during myelination, demyelination, re-myelination and dysmyelination processes and we reviewed the terminology previously used.We tried to include all studies reporting ultrastructural findings with no limitation to the experimental conditions, the species used and the disorders. The terminology used to describe the structural findings included compacted myelin, partially compacted myelin, noncompacted myelin, redundancy (hypermyelination, tomacula, myelinosome), splitting, complete circular splitting, myelin degradation, concentric lamellar bodies (myelin figures), loss of myelin lamellae, polyaxonal Schwann cells and necrotic cell debris.Ultrastructural data described in this paper aimed to provide a guide for future studies. We concluded that the evaluation of ultrastructural changes in any neurological disorder is greatly valuable for a better understanding of pathological and physiological changes occured. We also believe that supporting the ultrastructural findings with quantitative methods in the future will be of great value.

Histological evaluation of combined platelet-rich fibrin membrane and piezo-incision application in orthodontic tooth movement.

The aim of this study was to evaluate the effect of platelet-rich fibrin (PRF) membrane on tooth movement in comparison with shunt control and piezoelectric surgery. Sixteen White Vienna rabbits were included in the study and divided into two groups. Reciprocal forces (20 g) were applied on the maxillary incisors by an orthodontic appliance. In group 1, PRF membrane was placed sub-periosteally on the distal alveolar bone surface of the right central incisors and the left side was kept as control. In group 2, piezo-incisions 3 mm in depth were performed and combined with PRF membrane on the distal alveolar bone surface of the right central incisors, while the left side was kept as control. All rabbits were euthanized on day 21 and bilateral alveolar bone segments from the distal regions were removed for histological evaluation. Isolated PRF membrane application increased the blood vessel (8.3 ± 1.0; P = 0.026), osteoblast (6 ± 0.8; P = 0.027), and osteoclast (2.3 ± 0.8; P = 0.026) counts significantly compared to shunt control. Combined application of PRF membrane + piezo-incision increased the blood vessel (15.3 ± 0.8; P = 0.027), osteoblast (9.8 ± 1.4; P = 0.026), and osteoclast (3.3 ± 0.8; P = 0.024) counts significantly compared to shunt control. The increases in blood vessel count and osteoblast cell count were more evident in the combined application group (both P = 0.002). PRF membrane application significantly increased bone turnover, and the combined application of PRF membrane + piezo-incision was found to be the best method for increasing bone turnover.

The impact of TFPI on coronary atherosclerotic burden.

OBJECTIVES: We aimed to associate a coronary artery disease (CAD) presence and severity with endothelial dysfunction (ED), carotid intima media thickness (CIMT) and Tissue Factor Pathway Inhibitor (TFPI). BACKGROUND: ED has a central role in atherosclerosis. CIMT and TFPI activity are also related with atherosclerosis and CAD. METHODS: In our prospective observational study, 50 patients had CAD and 30 had normal coronary arteries. Endothelial function was evaluated by endothelium-dependent flow-mediated dilatation (FMD) and nitroglycerine-mediated dilatation (NMD) measurements. CIMT and Serum TFPI levels were also measured. RESULTS: TFPI was a statistically significant determinant between the two groups with an increased level in CAD (+) group (84.9 ± 19.3 vs 70.2 ± 14.7, p = 0.001). There was a positive correlation between CIMT and Gensini (r = 0.34, p = 0.014). There was a strong negative correlation between Gensini and FMD-NMD, statistically significant (FMD: r = -0.715, p < 0.001; NMD: r = -0.718, p < 0.001). CONCLUSION: We observed that ED, increased CIMT and TFPI levels were associated with CAD. Additionally, increased CIMT measurements and decreased FMD and NMD values had a positive correlation with GSS (Tab. 4, Fig. 6, Ref. 50).

Iloprost and vitamin C attenuates acute myocardial injury induced by suprarenal aortic ischemia-reperfusion in rabbits.

OBJECTIVE: The aim of this study was to evaluate antioxidant and cytoprotective effects of iloprost and Vitamin C in a distant organ after abdominal aorta ischemia-reperfusion injury. MATERIAL AND METHODS: Twenty-eight New Zealand rabbits weighing 2,400-2,800 g were used for this study. The rabbits were divided into four equal groups. These groups are control group, sham group, iloprost group, and iloprost+vitamin C group. Suprarenal aorta was occluded with a vascular clamp. Following 30 minutes of ischemia, the vascular clamp was removed. Rabbits in group 3 received 10 ng/kg/min iloprost and those in group 4 received 10 ng/kg/min iloprost and 10 mg/kg vitamin C. At the end of the reperfusion period, the rabbits were sacrificed by a high intraperitoneal dose of xylazine+ketamine injection. Myocardial tissue samples were taken for electron microscopic analysis. We evaluated SOD, MDA and catalase in myocardial tissue samples. RESULTS: Iloprost and iloprost+vitamin C groups significantly reduced the oxidative stress markers in tissue samples (p<0.05) and significantly decreased the myofibrillar injury and mitochondrial morphology changes in the myocardial tissue as shown with electron microscopy (p<0.05). Myocardial edema was significantly alleviated by iloprost and iloprost+vitamin C administration (p<0.05). CONCLUSIONS: This study clearly showed that myocardial injury and edema occurred after ischemia-reperfusion of abdominal aorta and that groups administered with iloprost and iloprost+vitamin C showed an attenuation of ischemia-reperfusion injury in distant organs (Tab. 3, Fig. 4, Ref. 30).

Effects of alendronate and pamidronate on apoptosis and cell proliferation in cultured primary human gingival fibroblasts.

Data arising from the recent literature directed the researchers to study on the degree and extent of bisphosphonate toxicity on oral mucosa in further detail. The aim of this study is to determine the half maximal inhibitory concentration of pamidronate (PAM) and alendronate (ALN) on human gingival fibroblasts in vitro using 3-[4.5-thiazol-2-yl]-2.5-diphenyltetrazolium bromide (MTT) assay and to evaluate the effects of both agents on the proliferation and apoptotic indices. Cells used in the study were generated from human gingival specimens and divided into alendronate (n = 240), PAM (n = 240), and control groups (n = 60). Based on the MTT assay results, 10(-4), 10(-5), 10(-6), and 10(-7) M concentrations of both drugs were administered and the effects were evaluated for 6, 12, 24, 48, or 72 h periods. An indirect immunofluorescence technique was used to evaluate apoptotic (anti-caspase 3) and proliferation (anti-Ki67) indices. Toxicity of both PAM and ALN was found to be the most potent at 10(-4)-10(-5) M range. The apoptotic index of PAM group was found to be significantly higher than ALN group for all concentrations especially at 24 h incubation time (p < 0.05). The decrease in the proliferation index was found similar in first 48 h for both drugs; however, after 72 h of incubation decrease in proliferation index in PAM group was found to be significantly higher (p < 0.05). Micromolar concentrations of not only PAM but also ALN rapidly affect cells generated from human oral gingival tissue by inducing apoptosis together with inhibition of proliferation. Cytotoxic effects of both ALN and PAM on primary human gingival fibroblasts, which cause significant changes in apoptotic and proliferative indices as shown in this in vitro study, suggests that the defective epithelialization of oral mucosa is possibly a major factor on the onset of bisphosphonate-related osteonecrosis of the jaw cases.

Effect of melatonin and time of administration on irradiation-induced damage to rat testes.

The effect of ionizing irradiation on testes and the protective effects of melatonin were investigated by immunohistochemical and electron microscopic methods. Eighty-two adult male Wistar rats were divided into 10 groups. The rats in the irradiated groups were exposed to a sublethal irradiation dose of 8 Gy, either to the total body or abdominopelvic region using a 60Co source at a focus of 80 cm away from the skin in the morning or evening together with vehicle (20% ethanol) or melatonin administered 24 h before (10 mg/kg), immediately before (20 mg/kg) and 24 h after irradiation (10 mg/kg), all ip. Caspace-3 immunoreactivity was increased in the irradiated group compared to control (P < 0.05). Melatonin-treated groups showed less apoptosis as indicated by a considerable decrease in caspace-3 immunoreactivity (P < 0.05). Electron microscopic examination showed that all spermatogenic cells, especially primary spermatocytes, displayed prominent degeneration in the groups submitted to total body and abdominopelvic irradiation. However, melatonin administration considerably inhibited these degenerative changes, especially in rats who received abdominopelvic irradiation. Total body and abdominopelvic irradiation induced identical apoptosis and testicular damage. Chronobiological assessment revealed that biologic rhythm does not alter the inductive effect of irradiation. These data indicate that melatonin protects against total body and abdominopelvic irradiation. Melatonin was more effective in the evening abdominopelvic irradiation and melatonin-treated group than in the total body irradiation and melatonin-treated group.

Effect of melatonin and time of administration on irradiation-induced damage to rat testes

The effect of ionizing irradiation on testes and the protective effects of melatonin were investigated by immunohistochemical and electron microscopic methods. Eighty-two adult male Wistar rats were divided into 10 groups. The rats in the irradiated groups were exposed to a sublethal irradiation dose of 8 Gy, either to the total body or abdominopelvic region using a 60Co source at a focus of 80 cm away from the skin in the morning or evening together with vehicle (20% ethanol) or melatonin administered 24 h before (10 mg/kg), immediately before (20 mg/kg) and 24 h after irradiation (10 mg/kg), all ip. Caspace-3 immunoreactivity was increased in the irradiated group compared to control (P < 0.05). Melatonin-treated groups showed less apoptosis as indicated by a considerable decrease in caspace-3 immunoreactivity (P < 0.05). Electron microscopic examination showed that all spermatogenic cells, especially primary spermatocytes, displayed prominent degeneration in the groups submitted to total body and abdominopelvic irradiation. However, melatonin administration considerably inhibited these degenerative changes, especially in rats who received abdominopelvic irradiation. Total body and abdominopelvic irradiation induced identical apoptosis and testicular damage. Chronobiological assessment revealed that biologic rhythm does not alter the inductive effect of irradiation. These data indicate that melatonin protects against total body and abdominopelvic irradiation. Melatonin was more effective in the evening abdominopelvic irradiation and melatonin-treated group than in the total body irradiation and melatonin-treated group.

Dose-dependent immunohistochemical and ultrastructural changes after oral methylphenidate administration in rat heart tissue.

Methylphenidate, more commonly known as Ritalin, is a piperidine derivative and is the drug most often used to treat attention deficit/hyperactivity disorder, one of the most common behavioural disorders of children and young adults. Our aims were to investigate dose-dependent immunohistochemical D2 expression and ultrastructural changes of the rat heart tissue, and to demonstrate possible toxicity of the long-term and high dose use of the methylphenidate. In this study, 27 female pre-pubertal Wistar albino rats, divided into three different dose groups (5, 10 and 20 mg/kg) and their control groups, were used. They were treated orally with methylphenidate dissolved in saline solution for 5 days/week during 3 months. At the end of the third month, after perfusion fixation, left ventricle of cardiac tissue was removed. Paraffin, semi-thin and thin sections were collected and immunohistochemical, terminal deoxynucleotidyl transferase-mediated Dig-dUTP nick end labelling assay and ultrastructural studies were performed. In conclusion, we believe that Ritalin is dose-related affecting dopaminergic system to increase heart rhythm and contraction. Thus, this drug may cause degenerative ultrastructural changes in mitochondrial path.