Effect of melatonin on the cardiotoxicity of doxorubicin.

This study was designed to investigate the preventive effect of melatonin on doxorubicin's most important side effect, cardiotoxicity. Forty male albino Wistar rats were utilized and the rats were divided into five groups: group I, 0.9% NaCl for 4 days; group II, doxorubicin 3 mg/kg/day for 4 days; group III, 2.5 % ethanol for 15 days; group IV, melatonin 6 mg/kg/day for 15 days; and group V, a doxorubicin and melatonin combination were administered intraperitoneally. At the end of the experiment, tissue samples obtained from the cardiac muscle of the left ventricle of the rats were processed for measurement of malondialdehyde and for electron microscopic examination. Malondialdehyde, a product of lipid peroxidation, was found to be significantly higher in the doxorubicin group. However, in the doxorubicin and melatonin combination group the level of malondialdehyde was decreased statistical significant. The histological examination revealed destruction of myofibrils, disorganization of sarcomeres, mitochondrial degeneration and formation of giant mitochondria and lipid accumulation in the doxorubicin group. Also, accumulation of filamentous structures in the sarcoplasma in some of the cells, structural changes in capillaries and an increase in collagen fibers forming bundles were observed. When melatonin was added to the doxorubicin treatment all structural changes were reduced. The cardiotoxic side effect of doxorubicin used as a chemotherapeutic agent and was probably developed as a result of suppression of the antioxidant system and lipid peroxidation. Therefore, it could be assumed that the addition of melatonin in the treatment of doxorubicin could prevent the cardiotoxicity of doxorubicin.

Antigen-presenting cells in the hypertrophic pharyngeal tonsils: a histochemical, immunuhistochemical and ultrastructural study.

The antigen presenting cells (APCs) with special interest to dendritic cells (DC), were investigated in 28 hypertrophic and 10 control pharyngeal tonsils of children by histochemistry, immunohistochemistry and electron microscopy. In this study, we are trying to clarify the function and classification of APC in pharyngeal tonsils using morphologic criteria, Human Leukocyte Antigen Monoclonal Antibody (HLA-DR MoAb), which is specific for APCs, and acid phosphatase (APh) reacting with both phagosomes and lysosomes. The surface epithelium of the patient group examined by light microscopy, heavy infiltration of lymphocytes, degenerated columnar cells and a few HLA-DR MoAb (+) columnar cells was observed. Additionally, a significant number of APCs which were Langerhans cells (LCs), interdigitating dendritic cell (IDC), follicular dendritic cell (FDC) and macrophages were stained with both HLA-DR MoAb and APh in the epithelial, interfollicular-subepithelial and follicular areas. Ultrastructural examinations revealed that lymphocytes, macrophages, LC and M cells were found among the surface columnar epithelial cells of the patient group. The interactions between M cells and LC suggested that M cells probably passed antigens from surface to LC. In the interfollicular-subepithelial areas of the hypertrophic pharyngeal tonsil, IDCs were in close contact with lymphocytes, macrophages and plasma cells. Seven types of FDCs (FDC-1 - FDC-7) were recognised according to their ultrastructural appearances. Differentiated FDCs (FDC-4) were also in close contact with each active subtype of FDCs in follicular areas besides lymphocytes. These findings supported the idea that although the pharyngeal tonsils contained several types of active APCs, only DC were in close contact with immunocompetent cells and the other APC's. Therefore, these morphologic appearances of DC could be a sign of function to initiate the immune response of the pharyngeal tonsil.

Ultrastructural evaluation of the effect of endosulfan on mice kidney.

In this study, the effect of the endosulfan on mice kidney was investigated at ultrastructural level. Moreover, biochemical analyses (G6PD, CAT, SOD, GSH and MDA) were determined in supernatant of kidney tissue. Endosulfan (13mg/kg/day body weight) was administered orally to mices via intragastric-during 10 days. The presence of mitochondrial degeneration in cytoplasm of proximal convoluted tubule cells were a striking feature. Furthermore, there was lipofuscin granules and membranous structures in some of proximal convoluted tubule cells. In some glomeruli, ultrastructural changes such as fusion in pedicels and focal thickening at glomerular basal membrane were seen. There were cytoplasmic bulges in some distal convoluted tubule cells. The biochemical results of the experimental group were significant when compared to the control. The effect of the endosulfan was mainly on the proximal convoluted tubule cells. Morever, the other parts of the nephron were effected. Thus, this degeneration in kidney may be thought that oxidative stress may play a role to the mediator in changing configuration of cell membrane and seem to account for the morphologic alteration of kidney.

Ultrastructural alterations in the myocardium of patients with sickle cell anemia.

Endomyocardial biopsies of patients with sickle cell anemia (SCA) were examined ultrastructurally. Myocardial fibers of patients revealed prominent degenerative changes such as nuclear chromatin condensation, myofibrillar degeneration, sarcosomal changes, dilatation of sarcoplasmic reticulum, formation of autophagic vacuoles, increase of lipofuscin granules and occurrence of vacuoles derived from endoplasmic reticulum and/or transverse tubules in some micrographs. Furthermore, edematous changes were developed at the same area where the degenerative changes were prominent. All of these cellular alterations could be related with ischemia resulting from local microvascular occlusion.

Ultrastructural evaluation of the effects of the contrast media on the rat kidney.

In this study, the ultrastructural observations in rat kidneys were studied 2, 24 and 48 h after intravenous injection of 1, 3 and 9 g iodine per kg body of ioxaglate and iohexol. The effect of the contrast media was mainly on the proximal convoluted tubule cells, the presence of vacuoles containing granular and membranous structures was a striking feature. In the distal convoluted tubular cells, pycnotic nuclei and cytoplasmic bulges toward the lumen were observed. In some glomeruli, membranous structures in cytoplasm of podocytes and thickening of glomerular basal membrane were seen. Values of biochemical analysis were slightly higher especially at high doses in experimental groups when compared to the control. The results suggest that iohexol causes more degeneration than ioxaglate. Not only proximal convoluted tubule cells but also the other parts of the nephron were affected by contrast media.

Ultrastructural and biochemical changes of the brain after peripheral administration of phorbol myristate acetate.

The ultrastructural and biochemical changes in the brain tissue of 20 mice were studied. The mice, separated into acute and chronic groups, were injected with phorbol myristate acetate (PMA) to trigger the release of free radicals. Malondialdehyde measurement and electron microscopic examination were applied for the evaluation of the effects of the free radicals. The level of lipid peroxide in the chronic PMA group was found to be significantly higher than it was in the acute PMA group (P < 0.005). An electron microscopic examination of the acute group revealed disruption of the mitochondrial cristae and dilatation of the endoplasmic reticulum in the neurons. Myelin sheaths of the nerve fibers exhibited focal structural changes. Neurons and neuroglial cells in the chronic group, however, exhibited distinct ultrastructural alterations. The ultrastructural and biochemical findings showed that free radicals lead to brain damage.

Ultrastructural and hormonal changes in the contralateral adrenal gland in unilateral adrenal gland ischemia: an experimental study in rats.

While it is well known that unilateral tissue ischemia may result in contralateral damage in some paired organs, there is no universally accepted mechanism to explain why these contralateral changes occur. The aim of the present study was to investigate the ultrastructural and hormonal changes that occur in the contralateral nonischemic adrenal gland after unilateral ischemia of an adrenal gland in a rat model. The animals were divided into four groups of four rats each; namely, a control group which received a sham operation without any ischemic insult, a 2-h ischemic group, a 4-h ischemic group, and an 8-h ischemic group. The left adrenal blood vessels were ligated in all ischemia groups and blood samples were taken for hormonal study 2, 4, and 8 h later, after which bilateral adrenalectomy was performed to determine the ultrastructural changes. The plasma concentrations of aldosterone and cortisol were determined by radioimmunoassays. There was an increase in both aldosterone and cortisol levels related to the duration of the ischemia, but the differences among the groups were not statistically significant. Contralateral ultrastructural damage such as heterochromatin in nuclei, mitochondrial degeneration, endoplasmic reticulum cisternal widening, increased lipid droplets, and lysosomes, were demonstrated electron-microscopically after unilateral adrenal ischemia.

Ultrastructure of the nasopharyngeal orifice epithelium of the eustachian tube in otitis media with effusion.

Epithelial changes in nasopharyngeal orifice of eustachian tube in 15 patients with otitis media with effusion (OME) were studied. Ultrastructural examination of the epithelium revealed distinct alterations in the ciliated cells, intermediate cells and in the columnar cells with microvilli. The ciliated cells were the predominant cell type in the epithelium and were characterized by compound cilia and apical cytoplasmic bulgings with fine granular content. The intermediate cells showed more prominent lateral cytoplasmic bulgings. Cytoplasmic bulgings of both cell types eventually pinched off and set free as cytoplasmic bodies, similar to the cytoplasmic bodies derived from lymphocytes. As a result of epithelial destruction, the lumen of nasopharyngeal orifice was occupied by epithelial cellular debris among which leucocytic cells and cytoplasmic bodies with fine granular content. This accumulation in the lumen probably developed as a result of defective mucociliary activity which is due to compound cilia formation in the ciliated cells. Moreover, ultrastructural resemblance of cytoplasmic bodies derived from ciliated cells, intermediate cells and leucocytic cells indicates the possible role of these cells in common immune defence mechanisms in chronic otitis media with effusion.

The effect of toluene on the rat ovary: an ultrastructural study.

In this study, eighteen Wistar female albino rats were used to observe the ultrastructural effects of toluene on the rat ovaries. The animals were divided into experimental and control groups. The experimental group was exposed to 3,000 ppm toluene/m3 for 7 days and 8 h/day. At the end of the experiment the main ultrastructural findings related to the oocytes of the antral follicles of the experimental group were: abundant vacuoles, lytic areas, degenerative mitochondria in the ooplasm and blunt microvilli on the surface. Furthermore, the granulosa cells revealed prominent degenerative changes such as pyknotic nuclei, mitochondrial alterations and dilatation of the endoplasmic reticulum (ER) cisternae. It was interesting to note tht the ultrastructure of primordial follicles was almost similar in both experimental and control groups. All these findings suggested that, although toluene did not affect the primordial follicles, the growing follicles showed degenerative changes attributable to the inhalation of a toxic agent such as toluene.

Electron microscopy of psoriatic skin before and after psoralen/ultraviolet A treatment.

Skin biopsy specimens of patients with psoriasis receiving psoralen/ultraviolet A treatment were examined. A decrease in tonofilaments and keratohyaline granules and enlarged intercellular spaces were common findings in all cases. Hyperchromatic nuclei in the horny cells and hyperactive keratinocytes in the malpighian layer were also observed. Treatment resulted in normalization of keratinocytes and stimulation of melanocytes. Our study revealed that psoralen/ultraviolet A is effective and important in the treatment of psoriasis, but patients should be evaluated for atypical changes.

Alport's syndrome with bilateral macular hole.

In this study 8 patients with Alport's syndrome are presented. The ocular manifestations of these patients were retinal flecks, macular depigmentation, microspherophakia and anterior lenticonus. One patient revealed bilateral macular hole which was an unusual feature. Four patients had renal biopsies with the characteristic electron microscopic changes of the disease. According to these findings our conclusion is that Alport's syndrome is a disorder of selected basement membranes.

The effects of the pretreatment of intravenous high dose methylprednisolone on Na(+)-K(+)/Mg(+2) ATPase and lipid peroxidation and early ultrastructural findings following middle cerebral artery occlusion in the rat.

The sodium-potassium activated and magnesium dependent adenosine-5'-triphosphatase (Na(+)-K(+)/Mg(+2) ATPase EC.3.6.1.3.) activity and lipid peroxidation and early ultrastructural findings were determined in rat brain at the acute stage of ischaemia produced by permanent unilateral occlusion of the middle cerebral artery (MCA). The effects of the pretreatment with intravenous high-dose methylprednisolone (MP) on these biochemical indices and ultrastructural findings were also evaluated in the same model. The rats were divided into four groups. In group I, 10 rats were used to determine Na(+)-K(+)/Mg(+2) ATPase activity and the extent of lipid peroxidation by measuring the malondialdehyde (MDA) content and normal ultrastructural findings. In group II on 20 rats, only subtemporal craniectomy was done in order to determine the effects of the surgical procedure on these indices and findings. This group was treated intravenously with saline solution before occlusion. In group III with MCA occlusion, saline solution was administered intravenously to 20 rats in the same amount of methylprednisolone used in group IV, ten minutes before the occlusion. In Group IV, a single high-dose (30 mg/kg) of methylprednisolone was administered intravenously, ten minutes before occlusion in 20 rats. After occlusion of the middle cerebral artery, Na(+)-K(+)/Mg(+2) ATPase activity was decreased promptly in the first ten minutes in the ischaemic hemisphere and remained at a lower level than the contralateral hemispheres in the same group and the normal levels in group I, during 120 minutes of ischaemia. A single dose methylprednisolone pretreatment prohibited the inactivation of Na(+)-K(+)/Mg(+2) ATPase. On the other hand, there was significant difference in malondialdehyde content between group I and group III. Malondialdehyde levels were significantly increased following ischaemia and a non-significant increase was observed in the contralateral hemisphere. Methylprednisolone treatment significantly decreased malondialdehyde content on the side of the ischaemic hemisphere. We conclude that there is a positive relationship between membrane-bound enzyme Na(+)-K(+)/Mg(+2) ATPase activity, malondialdehyde content and early ultrastructural changes in the treated group with MP. These data suggest that the pretreatment injection of high doses (30 mg/kg) methylprednisolone contribute to the protection of the brain from ischaemia with stabilization of the cell membrane by effecting the lipid peroxidation and the activation of Na(+)-K(+)/Mg(+2) ATPase.