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Microwave ablation (MWA) is known as an alternative therapy to surgery to treat tumors. However, MWA-based therapy requires advanced approaches in order to prevent causing damage to healthy tissue around the tumor and selectively target the desired area. Nanoparticles are considered promising tools in biomedicine to fulfill these requirements. This study was carried out in order to analyze the effect of iron oxide nanoparticles on the temperature increment during radiofrequency ablation therapy with different salt solutions including NaCl and KCl as inorganics, and pictic acid (IP6) as organic. Iron oxide nanoparticles (IONPs) with a size of 42 nm, a surface area of 77.1 m2/g, and a high magnetic field absorption capability of 0.893 A/m were synthesized. According to the results, the magnetic nanoparticles from the IP6 solution have a higher number of charges in the recipes, and also, they reacted faster than the commercially available salt solutions like KCl and NaCl since six NaSO3 molecules are in the content of the IP6. With the absorption of 5-20 % higher electromagnetic power density depending on the content of salt solution with IP6 leads to 7-10 % temperature increase under 59 W microwave input power with 2 minutes exposure. This results show that the novelty of a dipole-dipole interaction of organic IP6 with IONPs improve the ablation performance.

Human embryonic stem cells are derived from inner cell mass of early stage blastocyst embryos. These cells are pluripotent and can differentiate into functional neurons and various nerve cells under appropriate conditions. However, one of the biggest challenges in this area is to establish a renewable, easy-to-culture, neural lineage-linked neural precursor cell population. It is therefore crucial to conveniently differentiate human embryonic stem cells into precursor cells, maintain them as a self-renewing population and achieve nerve cell types from different regions as a pure population. Cell signals and their associated molecules also play an important role in these events. For the generation of neural precursor cells, a better understanding of stem cell biology and the important pathways involved in differentiation into neural cells is required. This review focuses on the differentiation methods from stem cells to neural cells and the signaling pathways and molecules that are important in this process.

Oz (Ingilizce):OBJECTIVE: This experimental study was designed to evaluate radiation-induced kidney damage and the protective effect of apricot against it using histological parameters. MATERIAL and METHODS: Rats were divided into 6 groups each containing 10 Sprague Dawley rats as follows: Regc: Rats on a regular diet (control diet) for 28 weeks; control group. Regx: Rats on a regular diet for 28 weeks, XRE on last day of eighth week. Aprc: Rats on an apricot diet for 28 weeks; control for no XRE. Aprx: Rats on an apricot diet for 28 weeks, XRE on last day of eighth week. Reg+Aprc: Rats on a regular diet for 8 weeks, followed by an apricot diet for the following 20 weeks; control. Reg + Aprx: Rats on a regular diet for 8 weeks, XRE on last day of eighth week, followed by an apricot diet for 20 weeks. RESULTS: The kidneys of the control groups showed normal kidney histology, whereas Regx group showed major histopathological changes, such as glomerular collapse, hemorrhage, interstitial fibrosis and inflammatory infiltrates. The Aprx and Reg+Aprx groups showed smaller amounts of degeneration. CONCLUSION: In conclusion, we suggest that agents with antioxidant properties such as apricot may have a positive effect in the treatment of renal diseases.

AMAC: Dusuk doz radyasyon gastrointestinal sistem uzerinde zararli etkiler gostermektedir. YONTEMLER: Bu calismada, 60 adet Sprague-Dawley sican 6 gruba ayrildi. Grup 1: 28 hafta normal diyet alan grup. Grup 2: 20 hafta normal diyet alip, son 8 hafta normal diyet+radyasyon alan grup. Grup 3: 28 hafta kayisili diyet alan grup. Grup 4: 20 hafta kayisili diyet alip, son 8 hafta kayisili diyet+radyasyon alan grup. Grup 5: 8 hafta normal diyet alip, devam eden 20 hafta kayisili diyet alan grup. Grup 6: 8 hafta normal diyet alip, devam eden 20 hafta kayisili diyet+radyasyon alan grup. Deney sonunda mide dokulari cikarildi. Doku ornekleri rutin histolojik prosedurden gecirildi. Kesitlere hematoksilen-eozin (H-E) boyasi yapildi. Histopatolojik hasar (mukoza hasar, konjesyon, infiltrasyon, gastrik bezlerin dilatasyonu, hemoraji) skoru hesaplandi. Maksimum skor 15 idi. Istatistiksel analizler icin SPSS 13.0 ve MedCalc 11.0 programlari kullanildi. Tum veriler aritmetik ortalama±Standart hata olarak ifade edildi. BULGULAR: Grup 1, 3 ve 5’e ait kesitler normal histolojik gorunumdeydi. Grup 2’de radyasyona bagli yaygin mide hasari tespit edildi. Ortalama histopatolojik hasar skoru 8.20±0.32 idi. Grup 4 ve 6’ya ait hasar skoru sirasiyla 2.30±0.47 ve 2.20±0.66 idi. Grup 4 ve 6’ya ait hasar skoru, grup 2’den anlamli derecede dusuktu (P=0.0001). SONUC: Sonuc olarak, radyasyon ile olusan mide hasarinda kayisinin faydali oldugunu dusunmekteyiz.

Radiation has potentially irreversible detrimental effects. Prevention with antioxidants may be possible. We hypothesized that, apricot may be preventive or ameliorating against the radiation effects on the rat lungs ex- posed to low dose X-ray radiation. Sixty rats were placed into 6 groups for 28 weeks. Group1: regular diet; group 2: regular diet and X-ray exposure; group 3: apricot diet; group 4: apricot diet and X-ray exposure; group 5: apricot diet for 20 weeks, regular diet for 8 weeks; group 6: apricot diet for 20 weeks, regular diet for 8 weeks and X-ray exposure. There were severe peribronchial, paranchimal and alveolar changes in group 2. In group 4 lung histology was mostly normal, with some mild changes. The findings were also mild in group 6; although worse than group 4. Our results suggested that, dietary intake of apricot is beneficiary against undesired effects of radiation in the lungs.

WOS: 000277987300025, Objective: Melatonin, a hormone produced by the pineal gland, has been suggested to protect against development of hypertension and atherosclerosis. In this study, the effects of long-term melatonin deficiency for twelve months after pinealectomy on the alpha-adrenergic-contractions induced by phenylephrine, endothelium-dependent relaxation responses to acetylcholine and the morphological changes in the rat thoracic aorta were studied. Material and Metods: Rats were pinealectomized twelve months before the beginning of the vasomotor studies. Rings of arteries were mounted in isolated tissue baths for the measurements of isometric contractile force. The contractile responses to phenylephrine and endothelium-dependent relaxation responses to acetylcholine in the vessels were evaluated. Endothelial function was evaluated by vascular relaxation to acetylcholine. Histological examinations demonstrated the alterations of tunica media in the vessels of pinealectomized rats. Results: Thick and thin areas were observed in the transverse sections of vessels and the ratio of the widest media thickness to the narrowest was found significantly increased in pinealectomized group (2.85 +/- 056) when compared to the control group (1.65 +/- 0.10). In addition, alpha-smooth muscle actin and elastic lamellae staining of the media were attenuated in pinealectomized rats. Although contractile responses of vessels to phenylephrine in pinealectomized rats were lower than control group, significant difference was found for only one concentration (3x 10-8 mol l-1) of phenylephrine. There was no difference between the relaxation responses to acetylcholine in pinealectomized and control groups. Conclusion: These results show that long-term melatonin deficiency may cause some morphological changes in the tunics media of vessels. However, the function of endothelium and vascular responsiveness to proportional to-adrenergic stimulus seem to be mostly protected., Inonu UniversityInonu University [P-01/33], This study was supported by a grant from The Scientific Research Fund of Inonu University (P-01/33). We thank Prof Dr. Saim Yologlu for statistical analysis.

In this study, we intended to determine the possible preventive effects of dietary apricot on oxidative stress due to ethanol usage in rat testes. The animals were divided into six groups as follows: Group 1 was control. Group 2 received ethanol. Group 3 were fed with apricot diet for 3 months. Group 4 were fed with apricot diet for 6 months. Group 5 received ethanol and apricot diet for 3 months. Group 6 were fed apricot diet for 3 months, and then ethanol+apricot diet for 3 months. Following sacrification, the testes were treated for morphological (tubular and germ cell histology, Sertoli and Leydig cell counts) and biochemical (superoxide dismutase, glutathion peroxidase, catalase, malondialdehyde) analyses. In Group 2, severe histopathological changes in seminiferous tubules and germ cells were determined as well as tubular degeneration and atrophy. Sertoli and Leydig cell counts in the interstitial tissue were decreased. Biochemical parameters revealed tissue oxidative stress. Similar alterations existed in Group 5, although to a lesser extent. In Groups 1, 3 and 4, no histopathological alterations were noted. Results of Group 6 were similar to the controls. Apricot rich diet may have a preventive role on histopathological changes caused by alcohol in rat testes.

The aim of this study was to evaluate the effect of resveratrol on the tracheal tissue of rats exposed to cigarette smoke.40 adult Wistar albino rats were divided into four groups for an experiment of 6 weeks. Animals in group 1 were controls (n = 10). Rats in group 2 were exposed to cigarette smoke only, and rats in group 3 received daily intraperitoneal injections of resveratrol (10 mg/kg/d). Animals in group 4 were exposed to both cigarette smoke and intraperitoneal injections of resveratrol. Rats of all groups were sacrificed using cervical dislocation. The tracheas were removed and embedded in paraffin blocks. Sections of 4-5 mum thickness were prepared from the blocks. These sections were stained with hematoxylin and eosin, periodic acid-Schiff, and Alcian blue and viewed with a Leica DFC 280 light microscope.Tracheal sections showed that, in group 2 (cigarette smoke group), there was desquamation of epithelial cells into the tracheal lumen, loss of cilia in the epithelial layer, an increase of goblet cells, activation of serous glands at the submucosa, and cell infiltration. In group 4 (cigarette smoke + resveratrol group), all these findings also existed but only a few sections were affected. It was observed that cigarette smoking caused morphological changes such as epithelial degeneration in the upper airway. These morphological changes were correlated with the amount of toxic substances in the cigarette smoke.We found that resveratrol had a preventive role in the histopathological changes caused by cigarette smoking in the rat trachea.

The purpose of this study was to determine the pre- and postpubertal 1H magnetic resonance spectroscopic characteristics of the normal testis to establish baseline values for further clinical studies.The subjects consisted of male volunteers, of whom 19 were prepubertal with ages between 7 and 13 years and 24 were postpubertal with ages between 19 and 39 years. Their testes were evaluated at 1.5 T with magnetic resonance spectroscopy; in addition, testis volumes were measured. Major metabolite peaks were identified and their ratios were calculated. Metabolite differences of testis between pre- and postpubertal age were analyzed.Major constituents of spectra were 3.21 ppm choline and 0.9-1.3 ppm lipid peaks. At the echo time (TE) spectrum of 31 ms, choline/lipid ratios ranged from 0.35 to 8.30 (mean=1.87) in postpubertal males and from 0.06 to 5.45 (mean=0.88) in prepubertal males (P.013). At the TE spectrum of 136 ms, choline/lipid ratios ranged from 0.66 to 15.42 (mean=4.09) in postpubertal males and from 0.05 to 4.91 (mean=0.9) in prepubertal males (P.016).Choline/lipid ratio was higher in the postpubertal period. The existence of higher choline peak in that age group should be due to the initiation of spermatogenesis. The decrease in the lipid peak may represent the effect of testosterone on testicular tissue or may be due to histochemical changes initiated by puberty. The significant decrease in choline/lipid ratio noted after puberty could represent the presence of spermatogenesis. This hypothesis should be evaluated by further studies on postpubertal subjects with impaired spermatogenesis.

Aim: In this study, we aimed to determine changes inhe number of villi, height of villi, width of villi and the number of goblet cells in rat ileum. Materials and Methods: For this purpose, 24 female Sprague Dawley rats were divided into 3 groups each containing 8 rats. Tissue samples were removed on the 21st day, 60th day and at 19 months. Sections were stained by the hematoxylin-eosin and periodic acid Schiff (PAS). The number of villi, height of villi, width of villi and number of goblet cell were determined by Leica Q Win image analysis system. Results: In the present study, the mean number of villi was 9.50±0.202 at 21 days old, 7.50±0.164 at 60 days old and 7.07±0.180 at 19 months old rats. There was a statistically significant difference between 21 days old and 60 days old groups, and 21 days old and 19 months old groups (p=0.0001). We have detected that the mean villi heights as 320.73±3.801 μm at 21 days old, 509.34±4.207 μm at 60 days old and 381.09±3.528 μm at 19 months old rats. All three groups had statistically significant differences compared with each other (p=0.0001). We have detected that the mean villi width as 86.75±1.665 μm at 21 days old, 110.08±1.331 μm at 60 days old and 100.51±2.140 μm at 19 months old rats. All three groups had a statistically significant difference compared with each other (p=0.0001). We have detected that mean number of goblet cells as 14.83±0.184 at 21 days old, 24.42±0.239 at 60 days old and 18.70±0.241 at 19 months old rats. All three groups had a statistically significant difference compared with each other (p=0.0001). Conclusion: The collected data shall provide a reference point for future studies. Key words: Ileum; Goblet Cell; Villi; Rat; Histomorphology., Amaç: Bu çalışmada, sıçan ileumunda yaşa bağlı olarak değiştiği düşünülen villusların sayısını, yüksekliğini, genişliğini ve goblet hücre sayısını incelemeyi amaçladık. Gereç ve Yöntem: Bu amaçla 24 adet dişi Sprague Dawley cinsi sıçanlar her grupta 8'er sıçandan oluşan 3 gruba ayrıldılar. Sıçanlar 21 günlük, 60 günlük ve 19 aylık olduklarında ileum dokuları çıkarıldı. Kesitler hematoksilen-eosin (H-E) ve periodic acid Schiff (PAS) ile boyandı. Leica Q Win görüntü analiz sistemi kullanılarak ortalama villus sayısı, villus yüksekliği, villus genişliği ve villuslardaki ortalama goblet hücre sayısı belirlendi. Bulgular: Bu çalışmada, ortalama villus sayısını 21 günlük grupta 9.50±0.20, 60 günlük grupta 7.50±0.16 ve 19 aylık grupta 7.07±0.18 olarak tespit ettik. 21 günlük grup ile 60 günlük grup ve 21 günlük grup ile 19 aylık grup arasında istatistiksel olarak anlamlı fark vardı (p=0.0001). Villus yüksekliğini 21 günlük grupta 320.73±3.80 μm, 60 günlük grupta 509.34±4.20 μm ve 19 aylık grupta 381.09±3.52 μm olarak tespit ettik. Grupları birbirleriyle karşılaştırdığımızda villus yüksekliği açısından aralarında istatistiksel olarak anlamlı fark vardı (p=0.0001). Villus genişliğini 21 günlük sıçanlarda 86.75±1.66 μm, 60 günlük sıçanlarda 110.08±1.33 μm ve 19 aylık sıçanlarda 100.51±2.14 μm olarak tespit ettik. Grupları birbirleriyle karşılaştırdığımızda villus genişliği açısından aralarında istatistiksel olarak anlamlı fark vardı (p=0.0001). Her villustaki ortalama goblet hücre sayısını 21 günlük grupta 14.83±0.18, 60 günlük grupta 24.42±0.23 ve 19 aylık grupta 18.70±0.24 olarak tespit ettik. Grupları birbirleriyle karşılaştırdığımızda aralarında istatistiksel olarak anlamlı fark vardı (p=0.0001). Sonuç: Elde edilen veriler sindirim sistemi ile ilgili çalışmalara referans oluşturacaktır. Anahtar kelimeler: İleum; Goblet Hücresi; Villus; Sıçan; Histomorfoloji.

Glutamate excitotoxicity has been postulated to underlie the neuronal death that occurs after ischemia. The most sensitive tissues to ischemic injury are hippocampus and cerebellum, whereas cerebrum is more resistant. We studied the glutamate-induced ultrastructural alterations in rat parietal and cerebellar neurons comparatively. We observed that glutamate (45 min, 10 -7 M) causes considerable nuclear, mitochondrial and cytoplasmic changes in both the neuron types. Mitochondrial and nuclear changes were particularly more severe in cerebellar granular, than the ones in parietal neurons. It has been concluded that glutamate induces necrotic changes in both parietal and cerebellar neurons. But cerebellar cortex was found to be more sensitive to glutamate excitotoxicity than cerebral cortex. We suggest that mitochondrial damage is, probably, an important factor in neuron necrosis, which is mediated by glutamate excitotoxicity.

Summary To evaluate the protective effects of Resveratrol (RES) on azoxymethane (AOM)-induced testicular damage using histopathology and biochemical analyses, 28 male rats were randomly divided into four groups. Groups were control, RES, AOM and ARES. At the end of the 7 weeks, following routine tissue processing procedure, testis sections were stained with haematoxylin–eosin and Masson's trichrome. The blood samples were taken for biochemical analysis of testosterone, total oxidative stress, total antioxidant status and oxidative stress index. Degenerative changes in the seminiferous tubules such as atrophy, loss in the number of germ cells and arrested spermatogenic cell, and increase in the connective tissue of the tunica albuginea in the groups with AOM treatment were found. RES treatment (ARES) reduced the number of affected seminiferous tubules significantly (p

Exposure to low x-ray doses damages the spermatozoa, mainly by late-onset (ie, after 3 months) oxidative stress. Antioxidants ameliorate oxidation and prevent tissue damage. Prunus armeniaca L (apricot), rich in carotenoids and vitamins, is a potent natural antioxidant. We hypothesized that an apricot-rich diet might ameliorate the detrimental effects of low-dose x-rays on testis tissue. A 20% apricot diet was composed isoenergetically to the regular rodent diet. The total phenolic content, reducing power, and antioxidant capacity of both diets were determined. Sprague-Dawley rats received apricot-rich diets before and after x-ray exposure. Regular diets were given to controls. Rats were exposed to 0.2 Gy x-rays at the eighth week and were euthanized at the 20th postexposure week. Testicular oxidative status was determined by tissue thiobarbituric acid-reactive substances, reduced glutathione, superoxide dismutase, and catalase activities. For histologic evaluation, qualitative and quantitative microscopic determinations were performed, and Leydig and Sertoli cell counts and Johnsen scores were measured. The control diet group had significant testicular oxidative stress and mild tissue deterioration. Leydig and Sertoli cell counts, tubule diameters, and Johnsen scores were significantly decreased in the exposure groups. Apricot-rich diet significantly ameliorated the oxidative status and prevented the damage in tubular histology. The protective effects were prominent when the diet was maintained throughout the time course and were partially protected when the diet was initiated after exposure. The natural antioxidant activity of apricot ameliorates the delayed detrimental effects of low-dose irradiation on testis tissue. The high total antioxidant capacity of the apricot deserves further investigation.

The aim of this study was to evaluate the effect of resveratrol on kidney tissue of rats exposed to cigarette smoke. Forty adult male Wistar Albino rats were divided into four groups. Animals in group 1 was the control group. For 6 weeks, group 2 was exposed to cigarette smoke; group 3 received daily intraperitoneal injections of resveratrol (10 mg/kg/d); and group 4 was exposed to both cigarette smoke and intraperitoneal resveratrol. All rats were sacrificed with cervical dislocation. The kidney tissues were obtained, fixed in Bouin’s fixative and embeded in paraffin blocks. Samples were sectioned to 4-5 microns thickness, stained with hematoxylin/eosin (H/E), Masson’s trichromic, periodic acid-schiff (PAS) and were examined by light microscopy for tubular injury and interstitial fibrosis. Results were compared by non-parametric tests. Hydropic degeneration, tubular atrophy, tubulo-interstitial fibrosis, interstitial cell infiltration, vacuolar degeneration and desquamation were prominent in group 2. In group 4, hydropic degeneration, epithelial cell vacuolization and desquamation was not observed, but occasional tubular atrophy and dilation were observed. Our study suggests that, some morphological alterations in the rat kidney, due to cigarette smoke may be prevented by resveratrol.

Cyclosporine A (CyA) leads to liver injury, probably by causing the production of free radicals and resulting in nitric oxide (NO) deficiency. We evaluated CyA-mediated liver damage histopathologically to determine the possible beneficial effects of l -arginine ( l -Arg). In this study, 7 groups of Sprague–Dawley rats; (1) Control group; (2) 0.9% NaCl group; (3) CyA group: 7.5 mg/kg/day; (4) l -Arg group: 2 g/lt/day; (5) l -NAME (N-nitro- l -arginine methyl ester) group: 5 mg/100 ml/day; (6) CyA+ l -Arg group: l -Arg (2 g/lt/day)+CyA (7.5 mg/kg/day); and (7) CyA+ l -NAME group: CyA (7.5 mg/kg/day)+ l -NAME (5 mg/100 ml/day) were included. At the end of the treatments, animals were killed and hepatic tissues were treated for morphological (hematoxylin and eosin) and biochemical (NO and malondialdehyde, MDA) analyses, and serum was processed for biochemical (alanine transaminase (ALT), aspartate transaminase (AST), bilirubin, alkaline phosphatase (ALP) and total protein) study. The results indicated that CyA-induced hepatotoxicity was characterized by sinusoidal dilatation, hepatocellular vacuolization, neutrophilic infiltration and hepatocellular necrosis. These findings were less pronounced in the CyA+ l -Arg group than CyA alone group. l -NAME group showed moderate changes. The CyA+ l -NAME (Group 7) had more severe changes. We found changes in tissue NO and MDA levels. We think that the tissue damage caused by CyA is mild and reversible at the period when biochemical parameters are just starting to become abnormal and that l -Arg may have a protective effect against CyA damage on liver.

Background: One of the major adverse effects of long term cyclosporine A (CyA) administration is chronic nephrotoxicity. Several studies have suggested that alterations of the L-arginine (L-Arg) nitric oxide (NO) pathway may be involved in the pathogenesis of CyA-induced kidney damage. Aim: We postulated that in vivo activation of L-Arg-NO pathway might have a beneficial effect on CyA-induced renal damage. Conditions of chronic NO enhancement was established with L-Arg supplementation and chronic NO blockade with N-nitro-L-Arg methyl ester (L-NAME). We tested the hypothesis that, if CyA administration alters intrarenal NO synthesis, then exogenous L-Arg supplementation could limit renal injury, on the contrary, L-NAME, a potent competitive inhibitor of NO synthesis, could enhance CyA nephrotoxicity. Harmful effect of NO blockade indirectly supports the beneficial effect of NO in a model of CyA nephrotoxicity. Methods: Rats were administered vehicle (VH), CyA (7.5 mg/kg/day), CyA + L-Arg (2g/kg/day), CyA + L-NAME (5 mg/100 ml/day), CyA + L-Arg + L-NAME, VH + L-Arg, VH + L-NAME and were sacrificed at the end of the experiment. Body weight, serum creatinine, blood urea nitrogen (BUN) and NO levels were determined. Tubular injury and interstitial fibrosis were evaluated semiquantitatively using scoring systems on paraffin sections stained with hematoxylin/eosin (H/E), Masson’s trichromic and periodic acid-Schiff (PAS). Results: The CyA group developed marked renal injury, characterized by a significant increase in serum creatinine and BUN, and histopathological alterations including tubular dilatation, vacuolization, necrosis, interstitial cell infiltration and tubulointerstitial fibrosis. CyA reduced serum NO level. L-Arg treatment significantly enhanced NO biosynthesis and protected animals from CyA-induced kidney damage. In contrast L-NAME strikingly reduced serum NO level, and worsened biochemical and histopathological alterations. Conclusion: Chronic CyA nephrotoxicity can be aggravated by NO blockade and ameliorated by NO enhancement suggesting that L-Arg supplementation may be protective in CyA nephrotoxicity.

Glutamate excitotoxicity has been postulated to underlie the neuronal death that occurs after ischemia. The most sensitive tissues to ischemic injury are hippocampus and cerebellum, whereas cerebrum is more resistant. We studied the glutamate-induced ultrastructural alterations in rat parietal and cerebellar neurons comparatively. We observed that glutamate (45 min, 10-7 m) causes considerable nuclear, mitochondrial and cytoplasmic changes in both the neuron types. Mitochondrial and nuclear changes were particularly more severe in cerebellar granular, than the ones in parietal neurons. It has been concluded that glutamate induces necrotic changes in both parietal and cerebellar neurons. But cerebellar cortex was found to be more sensitive to glutamate excitotoxicity than cerebral cortex. We suggest that mitochondrial damage is, probably, an important factor in neuron necrosis, which is mediated by glutamate excitotoxicity.

Cyclosporin A (CsA)-induced nephrotoxicity may be the consequence of oxidative stress. Anti-oxidant agents could be useful in reducing CsA toxicity. In this light microscopy study, tubular dilatation, atrophy, vacuolization and tubulointerstitial fibrosis were observed in rats given CsA, whereas in rats given CsA plus melatonin, no histological changes occurred. It is concluded that melatonin could be useful for reducing the nephrotoxic effects of CsA.